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Medulloblastoma is the most common malignant pediatric brain tumor and has been linked to known cancer predisposition syndromes. We report a case of medulloblastoma of a 12-year-old Indo-Trinidadian female with a strong family history of colorectal carcinoma. In collaboration with the SickKids-Caribbean Initiative (SCI), her tumor was confirmed to be a WHO grade 4 medulloblastoma - Wnt subtype. Genetic testing further confirmed the presence of a pathogenic APC gene variant [c.3183_3187del (p.Gln1062*)] which led to a diagnosis of Turcot syndrome type 2. The index patient received multimodal therapy which included surgery, radiation and chemotherapy and is currently post end-oftreatment and in remission. This case report aims to highlight the complexity of diseases and the need for expertise in identifying them in low-and-middle income countries, the need for access to specialized testing and the benefits of collaborating between low-and-middle income and high-income countries when managing complex oncology patients. [ABSTRACT FROM AUTHOR]

Medulloblastoma is the most common malignant pediatric brain tumor and has been linked to known cancer predisposition syndromes. We report a case of medulloblastoma of a 12-year-old Indo-Trinidadian female with a strong family history of colorectal carcinoma. In collaboration with the SickKids-Caribbean Initiative (SCI), her tumor was confirmed to be a WHO grade 4 medulloblastoma – Wnt subtype. Genetic testing further confirmed the presence of a pathogenic APC gene variant [c.3183_3187del (p.Gln1062*)] which led to a diagnosis of Turcot syndrome type 2. The index patient received multimodal therapy which included surgery, radiation and chemotherapy and is currently post end-of-treatment and in remission. This case report aims to highlight the complexity of diseases and the need for expertise in identifying them in low-and-middle income countries, the need for access to specialized testing and the benefits of collaborating between low-and-middle income and high-income countries when managing complex oncology patients.

We herein report a patient with Lynch-like syndrome in whom a brain tumor (glioblastoma) developed after repeated resection of colorectal cancer. The patient had a significant family history of cancer. Immunohistochemical expression of mismatch repair proteins was decreased in both brain and colon tumors, but no pathogenic variant of the related genes was detected. Although brain tumors occasionally develop in Lynch syndrome, they have not been reported in cases of Lynch-like syndrome. This first report of Lynch-like syndrome with the development of glioblastoma suggests the need for further investigation on the surveillance of brain tumors in patients with this syndrome.

Described in the literature as a characteristic feature of adulthood, glioblastoma is the most common malignant brain tumour of this age group, accounting for less than 20% of all intracranial tumours and about 80% of all astrocytic neoplasms. Risk factors involved in the development of this type of tumour include certain genetic disorders such as Li-Fraumeni syndrome (an autosomal dominant syndrome, fortunately extremely rare but predisposing to various forms of cancer), Turcot syndrome or neurofibromatosis. On the other hand, radiotherapy in the past also seems to be a factor in the development of glioblastoma. It is predominantly found in the cerebral hemispheres, is rarely found in the brainstem and occurs exceptionally in the cerebellum. Scientific studies conducted globally have shown a male:female ratio of 1.26 in the US and 1.28 in Europe. The peak incidence is between 40 and 70 years of age, but cases have also been observed, less frequently, in children with predominantly brainstem involvement. In what follows I would like to present the case of a 68-yearold patient, admitted with the suspicion of a tumour formation with right temporo-parietal location, which was found to be a glioblastoma multiforme after CT, anatomopathological and immunohistochemical examinations. [ABSTRACT FROM AUTHOR]

We report a case of successful treatment of a 15-year-old female patient (body mass index 16) diagnosed with Turcot syndrome (familial adenomatous polyposis of the colon) combined with multiple primary malignant tumors, including anaplastic astrocytoma (received combination therapy in 2007), metachronous cecal cancer (underwent subtotal colectomy and 12 courses of polychemotherapy in 2016–2017), and metachronous stage III pT3N1M0 rectal cancer at 8 cm. The patient underwent laparoscopic low resection with extirpation of the ileosigmoid anastomosis, creation of a reservoir-rectal anastomosis, and preventive ileostomy. The patient had minimal intraoperative blood loss and uneventful postoperative period (with an accelerated rehabilitation protocol). She was discharged from a hospital on day 9. Considering previous treatment episodes and the disease stage, we also included into the treatment regimen adjuvant FOLFOX polychemotherapy in a reduced dose for 6 months. During one-year follow up, there was no evidence of disease progression. Later, the patient underwent ileostomy closure with forming a side-to-side mechanical anastomosis. The patient is fully rehabilitated in term of her social activity.

Central nervous system tumors are the most common solid tumors in pediatrics and represent the largest cause of childhood cancer-related mortality. Improvements have occurred in the management of these patients leading to better survival, but significant morbidity persists. With the era of next generation sequencing, considerable advances have occurred in the understanding of these tumors both biologically and clinically. This information has impacted diagnosis and management. Subgroups have been identified, improving risk stratification. Novel therapeutic approaches, specifically targeting the biology of these tumors, are being investigated to improve overall survival and decrease treatment-related morbidity. The intent of this review is to discuss the genetics of common pediatric brain tumors and the clinical implications. This review will include known genetic disorders associated with central nervous system tumors, neurofibromatosis, tuberous sclerosis, Li-Fraumeni syndrome, Gorlin syndrome, and Turcot syndrome, as well as somatic mutations of glioma, medulloblastoma, and ependymoma. [ABSTRACT FROM AUTHOR]

Defined as a tumour with increased malignancy potential in childhood, medulloblastoma was first reported in the literature by Percival Bailey and Harvey Cushing in 1925. Scientific studies over the years have shown that this type of tumour represents about 20% of all intracranial tumours encountered in childhood, their percentage decreasing with advancing age. The genetic factor plays an important part in the appearance of medulloblastoma; there are certain diseases, in the patient’s history, that can be associated with this type of tumour. Here, we can specify Turcot syndrome (an autosomal recessive disease, rarely encountered) or basal cell carcinoma syndrome. This article presents the case of a young patient (41-year-old) suffering from a cerebellar tumour formation that turned out to be, after histopathological examination, a medulloblastoma. In practice we can find several types of medulloblastoma (desmoplastic or nodular, anaplastic, classical or undifferentiated). In what follows I will try to highlight a few aspects of a classic medulloblastoma. [ABSTRACT FROM AUTHOR]

The reported risk factors for glioblastoma (GBM), i.e., ionizing radiation, Li-Fraumeni syndrome, Neurofibromatosis I, and Turcot syndrome, also increase the risk of other brain tumor types. Risk factors for human GBM are associated with different oncogenic mutation profiles. Pedigreed domestic dogs with a shorter nose and flatter face (brachycephalic dogs) display relatively high rates of glioma formation. The genetic profiles of canine gliomas are also idiosyncratic. The association of putatively different mutational patterns in humans and canines with GBM suggests that different oncogenic pathways can result in GBM formation. Strong epidemiological evidence for an association between exposure to chemical carcinogens and an increased risk for development of GBM is currently lacking. Ionizing radiation induces point mutations, frameshift mutations, double-strand breaks, and chromosomal insertions or deletions. Mutational profiles associated with chemical exposures overlap with the broad mutational patterns seen with ionizing radiation. Weak statistical associations between chemical exposures and GBM reported in epidemiology studies are biologically plausible. Molecular approaches comparing reproducible patterns seen in spontaneous GBM with analogous patterns found in GBMs resected from patients with known significant exposures to potentially carcinogenic chemicals can address difficulties presented by traditional exposure assessment., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Colorectal cancers (CRCs) develop through the accumulation of genetic and epigenetic alterations of oncogenes and tumor suppressor genes. In addition to the well-characterized adenoma-carcinoma sequence, the serrated neoplasia pathway is now recognized as an alternative pathway for CRC development. Summary: Through analysis of the colonoscopic, pathological, and molecular features of colorectal tumors, we identified a novel microsurface structure characteristic of serrated lesions. The Type II-Open (Type II-O) pit pattern is highly specific to sessile serrated adenoma/polyps (SSA/Ps), and Type-II-O-positive tumors frequently exhibit v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation and 5′-C-phosphate-G-3′ (CpG) island hypermethylation. By screening DNA methylation associated with the development of serrated lesions, we detected methylation of secreted protein acidic and rich in cysteine (SPARC)-related modular calcium binding 1 (SMOC1) in traditional serrated adenomas (TSAs). Epigenetic silencing of SMOC1 is prevalent among TSAs but it is rarely observed in SSA/Ps, which suggests SMOC1 could be a useful diagnostic marker of serrated lesions. We also searched for epigenetic alterations associated with the growth pattern of colorectal tumors and found that methylation of neurotensin receptor 1 is associated with lateral and non-invasive tumor growth. Key Message: Through the summarized studies, we have been able to identify novel morphological and molecular features that could contribute to a better understanding of colorectal tumors and to improved clinical diagnosis. [ABSTRACT FROM AUTHOR]

Turcot syndrome and fistulizing Crohn’s disease (CD) are two disease entities that are not usually associated with one another, particularly given the rarity of the former. This is a case of a pediatric patient with fistulizing CD treated with biologic therapy, who was later found to have Turcot syndrome. Management of this rare combination of diseases can present several challenges, as surgical options may be limited and chronic immunosuppression to treat CD may lead to accelerated progression of malignancy in Turcot syndrome. This unique case highlights the importance of weighing the risks and benefits involved in treating two disease entities that impact one another.

Turcot’s syndrome is a rare genetic disorder clinically characterised by concomitant occurrence of primary brain tumour and colorectal polyposis. It is commonly seen in association with two other syndromes, namely, hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP). It is characterized by an increased risk for early onset of other tumours including of endometrium, stomach, small intestine, hepatobiliary system, kidney, ureter, brain and ovary. We report the rare occurrence of Turcot syndrome in a 13-year-old girl who presented with focal seizure.

Abstract Background A subset of patients who undergo colon cancer surgery may be at a high risk of multiple subsequent admissions. We developed a simplified model to predict the preoperative risk of multiple postoperative admissions (MuAdm) among patients undergoing colon resection to aid in preoperative planning. Methods Patients aged ≥18 y with colon cancer who underwent elective surgical resection identified in discharge claims from California and New York (2008-2011) were included. The primary outcome, MuAdm, was defined as 2 or more admissions in the year following resection. Logistic regression models were developed to identify factors predictive of MuAdm. A weighted point system was developed using beta-coefficients (P < 0.05). A random sample of 75% of the data was used for model development, which was validated in the remaining 25% sample. Results A total of 14,780 patients underwent colon resection for cancer. Almost 30% had an admission in the year after index surgery and 9.8% had MuAdm. The significant predictors of MuAdm were higher Elixhauser comorbidity index score, metastatic disease, payer system, and the number of admissions in the year before surgery. Scores ranged from 0 to 8. Scores ≤1 had a 7% risk of MuAdm, and scores ≥6 had a >30% risk of MuAdm. Conclusions In the year following discharge after resection of colon cancer, nearly 10% of patients are admitted 2 or more times. A simple, preoperative clinical model can prospectively predict the likelihood of multiple admissions in patients anticipating resection. This model can be used for preoperative planning and setting postoperative expectations more accurately. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) incidence rates have declined in recent years for people of all races/ethnicities; however, the extent to which the decrease varies annually by demographic and disease-related characteristics is largely unknown. This study examines trends and annual percent change (APC) in the incidence among persons diagnosed with CRC in the United States of America from 2000-2014. The data obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program were analyzed, and all persons (N = 577,708) with malignant CRC recorded in the SEER 18 database from 2000 to 2014 were characterized according to sex, race, age at diagnosis, disease site and stage. Incidence rates and APC were calculated for the entire study period. Overall, the incidence rate of CRC decreased from 54.5 in 2000 to 38.6 per 100,000 in 2014, with APC = 􀀀2.66 (p < 0.0001). Decline in rates was most profound between 2008 and 2011 from 46.0 to 40.7 per 100,000 (APC = 􀀀4.04; p < 0.0001). Rates were higher for males (vs. females; rate ratio (RR) = 1.33) and for blacks (vs. whites; RR = 1.23). Proximal colon cancers at the localized stage were the predominant cancers. An increase in rate was observed among people younger than 50 years (6.6 per 100,000, APC= 1.5). The annual rate of CRC has decreased over time. However, the development and implementation of interventions that further reduce the disparities among demographic and disease-related subgroups are warranted. [ABSTRACT FROM AUTHOR]

Colorectal cancers comprise a complex mixture of malignant cells, nontransformed cells, and microorganisms. Fusobacterium nucleatum is among the most prevalent bacterial species in colorectal cancer tissues. Here we show that colonization of human colorectal cancers with Fusobacterium and its associated microbiome--including Bacteroides, Selenomonas, and Prevotella species--is maintained in distal metastases, demonstrating microbiome stability between paired primary and metastatic tumors. In situ hybridization analysis revealed that Fusobacterium is predominantly associated with cancer cells in the metastatic lesions. Mouse xenografts of human primary colorectal adenocarcinomas were found to retain viable Fusobacterium and its associated microbiome through successive passages. Treatment of mice bearing a colon cancer xenograft with the antibiotic metronidazole reduced Fusobacterium load, cancer cell proliferation, and overall tumor growth. These observations argue for further investigation of antimicrobial interventions as a potential treatment for patients with Fusobacterium-associated colorectal cancer. [ABSTRACT FROM AUTHOR]

Two-stage least squares estimation is popular for structural equation models with unmeasured confounders. In such models, both the outcome and the exposure are assumed to follow linear models conditional on the measured confounders and instrumental variable, which is related to the outcome only via its relation with the exposure. We consider data where both the outcome and the exposure may be incompletely observed, with particular attention to the case where both are censored event times. A general class of two-stage minimum distance estimators is proposed that separately fits linear models for the outcome and exposure and then uses a minimum distance criterion based on the reduced-form model for the outcome to estimate the regression parameters of interest. An optimal minimum distance estimator is identified which may be superior to the usual two-stage least squares estimator with fully observed data. Simulation studies demonstrate that the proposed methods perform well with realistic sample sizes. Their practical utility is illustrated in a study of the comparative effectiveness of colon cancer treatments, where the effect of chemotherapy on censored survival times may be confounded with patient status. [ABSTRACT FROM AUTHOR]

In this article, we describe the influence of structure on biological behavior of amino acid-Pd complex and compare it with oxalipalladium. A new water-soluble oxalipalladium analog with formula of [Pd(DACH) (isopentylgly)](NO3), where DACH is 1R,2R-diaminocyclohexane, has been synthesized and characterized by elemental analysis, conductivity measurements, IR, UV-Vis, and 1H NMR spectroscopies. The interactions of oxalipalladium and its amino acid derivative with highly polymerized calf-thymus DNA have been extensively studied by spectroscopic methods. The high binding constants of oxalipalladium (0.38 x 104 M-1) and new amino acid-Pd complex (0.65 x 104 M-1) were determined using absorption measurements. Also circular dichroism (CD) studies show that Pd complex causes more disturbances on DNA structure rather than oxalipalladium. The experimental results proposed that [Pd(DACH)(isopentylgly)] (NO3) is bound to DNA by groove-binding mode as well as partially covalent interaction, while oxalate analog binds covalently to DNA after hydrolysis. Interaction of the two metal derivative complexes was studied by molecular docking simulation. The results showed that amino acid-Pd complex has higher negative docking energy and higher tendency for interaction with DNA, and exert more structural change on DNA. Finally, the anticancer and growth inhibitory activities of synthesized complexes were investigated against human colon cancer cell line of HCT116 after 24 h incubation time using MTT assay. Results show that the complex [Pd(DACH)(isopentylgly)](NO3) showed enhanced anticancer and growth inhibitory activities against human colon can cell line HCT116. [ABSTRACT FROM AUTHOR]

Rapid and objective detection of cancer is crucial for successful treatment. Near-infrared (NIR) spectroscopy is a vibrational technique capable of optically probing molecular changes associated with disease. The purpose of this study was to explore NIR spectroscopy for discriminating cancer from normal colorectal tissues. A total of 110 tissue samples from patients who underwent operations were characterized in this study. The popular ensemble technique AdaBoost was used to construct the diagnostic model. A decision stump was used as the weak learning algorithm. Adaboost with decision stump, an ensemble of weak classifiers, was compared with the most suitable single model, a strong classifier. Only the 20 most significant variables were selected as inputs for the model based on measured defined variable importance. Using an independent test set, the single strong classifier provided diagnostic accuracy of 89.1%, sensitivity of 100%, and specificity of 78.6%, whereas the ensemble of weak stumps provided accuracy of 96.3%, sensitivity of 96.3%, and specificity of 96.3% for distinguishing cancer from normal colorectal tissues. Therefore, NIR spectroscopy in combination with AdaBoost with decision stumps has demonstrated potential for rapid and objective diagnosis of colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: Recently, there is a great attention, about the clinicopathological differences between right and left colon cancer, and how much these differences will affect the outcomes of colon cancer patients. Many epidemiological studies have demonstrated, that tumor at the right and left colon, respectively, occur with different incidence in diverse region of the world. Differences in clinical presentation, patient's demographics, and tumor biology between right- and left- sided colon cancers have long been reported in the literatures. Methods: The current study was conducted in Clinical Oncology and Nuclear medicine department, Ain Shams University Hospitals, during the period from January 2011 to December 2015, data on all patients histologically confirmed with colon cancer, were evaluated right-and left-sided cancers were compared with regard to epidemiological, clinical and pathological parameters as well as survival data. Results: The study showed that, there was 129 patients, 70(54.2%) patients had left-sided colon cancers and 59(45.7%) patients had right-sided colon cancers, most of the cases were aged above 50 years 61.2%. Histopathological type was mainly adenocarcinoma 72.09%, moderately differentiated 79.8%, the mucinous carcinoma was more in right sided colon 56.25%. Comparison of progression free survival in stage IV, showed higher progression rate (58.3%) in right sided patients, than left sided patients (41.6%), this difference was not statistically significant. We also found that patients with right-sided colon cancer had a statistically significantly worse overall survival (OS) P value=0.019, than patients with left-sided colon cancer. We demonstrated that the differences in OS were significant only in patients with stage IV colon cancer. Conclusion: In conclusion, our results support evidence that there are differences in the biology and outcomes for right- and left-sided colon cancers. Significantly better survival is seen for metastatic colon cancer with a left-sided, and this was confirmed by multivariate analysis. This might have been due to several environmental and lifestyle factors, which contributed to this anatomical shift. The differences in genetic and molecular pathologic profiles in each side of the colon were observed. Stratification based on the primary site should be considered in the future for trials assessing survival for colon cancer. [ABSTRACT FROM AUTHOR]

Colorectal cancer is noted for being one of the most frequent of tumors, with expressive morbidity and mortality rates. In new drug discovery, plants stand out as a source capable of yielding safe and high-efficiency products. Well known in Brazilian popular medicine, Libidibia ferrea (Mart. Ex Tul.) L.P. Queiroz var. ferrea (better known as “ironwood” or “jucá”), has been used to treat a wide spectrum of conditions and to prevent cancer. Using methodologies that involved flow cytometry, spectrophotometry and RT-qPCR assays, crude extracts of the fruits of L. ferrea (20T, 40T, 60T and 80T) were evaluated at 24 h and/or 48 h for: their ability to inhibit cell proliferation; induce apoptosis through Bcl-2, caspase-3 and Apaf-1; their antioxidant activity and effects on important targets related to cell proliferation (EGFR and AKT) in the HT-29 human colorectal cancer lineage. The results revealed high antiproliferative potential as compared to the controls, induction of apoptosis through the intrinsic pathway, and probable tumor inhibition activity under the mediation of important targets in tumorigenesis. In addition, L. ferrea revealed antioxidant, lipid peroxidation and chemoprotective effects in healthy cells. Thus, L. ferrea derivatives have important anticancer effects, and may be considered promising candidate for colorectal cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Investigation of brain cancer can detect the abnormal growth of tissue in the brain using computed tomography (CT) scans and magnetic resonance (MR) images of patients. The proposed method classifies brain cancer on shape-based feature extraction as either benign or malignant. The authors used input variables such as shape distance (SD) and shape similarity measure (SSM) in fuzzy tools, and used fuzzy rules to evaluate the risk status as an output variable. We presented a classifier neural network system (NNS), namely Levenberg-Marquardt (LM), which is a feed-forward back-propagation learning algorithm used to train the NN for the status of brain cancer, if any, and which achieved satisfactory performance with 100% accuracy. Methods: The proposed methodology is divided into three phases. First, we find the region of interest (ROI) in the brain to detect the tumors using CT and MR images. Second, we extract the shape-based features, like SD and SSM, and grade the brain tumors as benign or malignant with the concept of SD function and SSM as shape-based parameters. Third, we classify the brain cancers using neuro-fuzzy tools. In this experiment, we used a 16-sample database with SSM ( μ) values and classified the benignancy or malignancy of the brain tumor lesions using the neuro-fuzzy system (NFS). Results: We have developed a fuzzy expert system (FES) and NFS for early detection of brain cancer from CT and MR images. In this experiment, shape-based features, such as SD and SSM, were extracted from the ROI of brain tumor lesions. These shape-based features were considered as input variables and, using fuzzy rules, we were able to evaluate brain cancer risk values for each case. We used an NNS with LM, a feed-forward back-propagation learning algorithm, as a classifier for the diagnosis of brain cancer and achieved satisfactory performance with 100% accuracy. The proposed network was trained with MR image datasets of 16 cases. The 16 cases were fed to the ANN with 2 input neurons, one hidden layer of 10 neurons and 2 output neurons. Of the 16-sample database, 10 datasets for training, 3 datasets for validation, and 3 datasets for testing were used in the ANN classification system. From the SSM ( µ) confusion matrix, the number of output datasets of true positive, false positive, true negative and false negative was 6, 0, 10, and 0, respectively. The sensitivity, specificity and accuracy were each equal to 100%. Conclusion: The method of diagnosing brain cancer presented in this study is a successful model to assist doctors in the screening and treatment of brain cancer patients. The presented FES successfully identified the presence of brain cancer in CT and MR images using the extracted shape-based features and the use of NFS for the identification of brain cancer in the early stages. From the analysis and diagnosis of the disease, the doctors can decide the stage of cancer and take the necessary steps for more accurate treatment. Here, we have presented an investigation and comparison study of the shape-based feature extraction method with the use of NFS for classifying brain tumors as showing normal or abnormal patterns. The results have proved that the shape-based features with the use of NFS can achieve a satisfactory performance with 100% accuracy. We intend to extend this methodology for the early detection of cancer in other regions such as the prostate region and human cervix. [ABSTRACT FROM AUTHOR]

Previous epidemiological studies have demonstrated that moderate coffee consumption is associated with a lower risk of certain types of cancer, particularly colon cancer. To elucidate the molecular basis for this protective action, the effect of coffee on Caco‑2 human colon carcinoma cells was investigated. Low concentrations of coffee (<5%) inhibited proliferation of Caco‑2 cells without affecting cell viability. Coffee also reduced KRAS proto‑oncogene, GTPase (KRAS) gene expression in a dose‑dependent manner; however, caffeine, caffeic acid and chlorogenic acid, three major constituents of coffee, did not exhibit this effect. Increasing the duration of coffee bean roasting increased the reduction in KRAS expression, suggesting that the active constituents responsible for this effect emerged during the roasting process. MicroRNA (miR) analysis revealed that coffee induced the expression of miR‑30c and miR‑96, both of which target the KRAS gene. The results of the present study suggested that daily coffee consumption may reduce KRAS activity, thereby preventing the malignant growth of colon carcinoma cells. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the expression of complement component 1, q subcomponent-binding protein (C1QBP) in colon cancer cells, and identify proteins that interact with C1QBP. Total proteins were extracted from both the tumor and normal tissues of 22 patients with colon cancer and analyzed using liquid chromatography-mass spectrometry (LC-MS) to identify proteins that were differentially-expressed in tumor tissues. C1QBP overexpression was induced in 293T cells using a pFLAG-CMV2 expression vector. Overexpressed FLAG-tagged C1QBP protein was then immunoprecipitated using anti-FLAG antibodies and C1QBP-interacting proteins were screened using LC-MS analysis of the immunoprecipitates. The C1QBP-interacting proteins were confirmed using reverse-immunoprecipitation and the differential expression of C1QBP in tissues and cell lines was confirmed using western blot analysis. LC-MS analysis revealed that C1QBP exhibited a typical tumor expression pattern. Two immune-reactive signals (33 and 14 kDa) were detected in normal and tumor tissues from 19 patients. Furthermore, 14 kDa C1QBP protein was upregulated in the tumors of 15 patients. In total, 39 proteins were identified as candidate C1QBP-interacting proteins, and an interaction between C1QBP and apolipoprotein A-I was confirmed. The present study indicates that C1QBP is involved in colon cancer carcinogenesis, and that the mechanisms underlying the established anti-tumor properties of apolipoprotein A-I may include interacting with and inhibiting the activity of C1QBP. [ABSTRACT FROM AUTHOR]

In this study, the effects of different doses of dual modification-treated (DMT) indica rice resistant starch (IR-RS) on azoxymethane (AOM)-induced early colon cancer in mice were investigated. The investigated factors included body weight, gastrointestinal emptying rate, the number and morphology of aberrant crypt foci (ACFs) and the specific expressions of adenomatous polyposis coli (APC), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and cytochrome c genes. The results demonstrated that DMT IR-RS controlled the increase in the body weights of the mice, increased the gastrointestinal emptying rates and reduced the numbers of ACFs and aberrant crypts. Reverse transcription-polymerase chain reaction revealed that DMT IR-RS promoted the expression of APC, Bax and cytochrome c and inhibited the expression of Bcl-2. These results demonstrate that a DMT IR-RS diet may induce apoptosis and has beneficial health effects in AOM-induced early colon cancer in mice. [ABSTRACT FROM AUTHOR]

Colon cancer patients have major unmet needs in terms of robust diagnostics and molecular biomarkers for personalized therapeutics. We have previously reported that human CAP10-like protein 46 kDa (hCLP46) is overexpressed in human acute myelogenous leukemia, T acute lymphoblastic leukemia, and leukemia cell lines. We extend this line of biomarker and diagnostic discovery research by investigating hCLP46 expression in colorectal cancer (CRC) tissues and examine the possibility of hCLP46 as a candidate biomarker for diagnosis and prognosis of CRC. Using a tissue microarray analysis approach, we found that hCLP46 is (1) overexpressed in 90 CRC tissues compared with 90 matched noncancerous tissues and (2) positively correlated with higher tumor-node-metastasis (TNM) stage, lymph node metastasis, and shorter survival time. Moreover, in vitro experiments demonstrated that downregulation of hCLP46 in CRC cells results in proliferation arrest and adhesion enhancement, while apoptosis is unchanged. Further transcriptome profile analysis corroborated that the adhesion pathway is related to hCLP46 downregulation. This report for the first time, to the best of our knowledge, demonstrates that hCLP46 promotes tumor malignancy in CRC cells. We suggest that hCLP46 is warranted for further research as a candidate biomarker for clinical phenotypes related to colon cancer. [ABSTRACT FROM AUTHOR]

Background: Constitutional mismatch repair deficiency syndrome results from bi-allelic inheritance of mutations affecting the key DNA mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. Individuals with bi-allelic mutations have a dysfunctional mismatch repair system from birth; as a result, constitutional mismatch repair deficiency syndrome is characterised by early onset malignancies. Fewer than 150 cases have been reported in the literature over the past 20 years. This is the first report of the founder PMS2 mutation - NM_000535.5:c.1500del (p.Val501TrpfsTer94) in exon 11 and its associated cancers in this family. Case presentation: The proband is 30 years old and is alive today. She is of Pakistani ethnic origin and a product of consanguinity. She initially presented aged 24 with painless bleeding per-rectum from colorectal polyps and was referred to clinical genetics. Clinical examination revealed two café-au-lait lesions, lichen planus, and a dermoid cyst. Her sister had been diagnosed in childhood with an aggressive brain tumour followed by colorectal cancer. During follow up, the proband developed 37 colorectal adenomatous polyps, synchronous ovarian and endometrial adenocarcinomas, and ultimately a metachronous gastric adenocarcinoma. DNA sequencing of peripheral lymphocytes revealed a bi-allelic inheritance of the PMS2 mutation NM_000535.5:c.1500del (p.Val501TrpfsTer94) in exon 11. Ovarian tumour tissue demonstrated low microsatellite instability. To date, she has had a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and a total gastrectomy. Aspirin and oestrogen-only hormone replacement therapy provide some chemoprophylaxis and manage postmenopausal symptoms, respectively. An 18-monthly colonoscopy surveillance programme has led to the excision of three high-grade dysplastic colorectal tubular adenomatous polyps. The proband's family pedigree displays multiple relatives with cancers including a likely case of 'true' Turcot syndrome. Conclusions: Constitutional mismatch repair deficiency syndrome should be considered in patients who present with early onset cancer, a strong family history of cancer, and cutaneous features resembling neurofibromatosis type I. Immunohistochemistry analysis of tumour and normal tissue is sensitive and specific for identifying patients with mismatch repair deficiency and should direct DNA sequencing of lymphocytic tissue to establish a diagnosis. Microsatellite instability status appears to be of little value in identifying patients who may have constitutional mismatch repair deficiency syndrome. [ABSTRACT FROM AUTHOR]

Background: Previous reports have revealed that down-regulation of miR-34a expression can promote colorectal cancer (CRC) cell growth by targeting cell cycle-related transcriptional factor E2F1. To date, the function of the single nucleotide polymorphism (SNP) located in the mature region of miR-34a has not been investigated. Methods: We performed a case-control study including 685 CRC patients and 618 cancer-free controls. Genotyping, real-time PCR assay, cell transfection, and the dual luciferase reporter assay were used in our study. Cell proliferation and cell cycle analysis were measured in CRC cells including Hct-116 and SW480. The overall survival of different genotypes was also investigated. Results: We found that the rs35301225 polymorphism in miR-34a was involved in the occurrence of CRC by acting as a tumor suppressor by down-regulation of tumor-promoting gene E2F1. C/A SNP of miR-34a could promote CRC cell proliferation by up-regulation of E2F1. Also, C/A genotype can change the cell cycle by increasing the S phase percentage. Moreover, the SNP in rs35301225 of miR-34a was associated with tumor size and tumor differentiation, as well as metastasis in CRC patients; C/A SNP was related to the significantly enhanced expression of E2F1 and shorter survival in post-surgery CRC patients. Conclusions: rs35301225 in miR-34a was highly associated with a decreased risk of CRC in a Chinese population and might serve as a novel biomarker for colon cancer. [ABSTRACT FROM AUTHOR]

Objective: To detect the expression of CD133, E-cadherin and WWOX in colorectal cancer, analyze the correlations and pathological significance of the biomarkers. Methods: Two hundred and ten patients with colorectal cancer treated surgically between January 2007 and December 2015 were analyzed retrospectively. All patients had pathologic specimens and integrated clinical data. Pathologic specimens were retrieved for immunohistochemical examination of the expressions of CD133, WWOX and E-cadherin. The clinical data of these patients including gender, age, tumor location, tumor size, tumor differentiation, invasion depth, hepatic metastases, lymphatic metastasis, UICC stage and recurrence of tumor were retrieved to investigate their demographics and clinical characteristics. Results: In 210 specimens of colorectal cancer, the positive expression rate of CD133, E-cadherin and WWOX was 61.9%, 40.5% and 41.9%, respectively. The expression of CD133, E-cadherin and WWOX was significantly correlated with lymphatic metastasis, hepatic metastases and UICC stage (p<0.05). The expression of CD133 was negatively correlated with WWOX and E-cadherin (p<0.05), and the expression of WWOX was positively correlated with E-cadherin in specimens (p<0.05). Conclusion: A detection of CD133, E-cadherin and WWOX can facilitate physicians in predicting the progression and prognosis of colorectal cancer. [ABSTRACT FROM AUTHOR]

Background and Aim We aimed to investigate the ability of fluoro-2-deoxy- d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) to detect synchronous neoplasms, specifically obstructive colorectal cancer (CRC) and CRC in the proximal colon and to suggest a management strategy based on FDG PET/CT findings. Methods From the CRC surgery database of our institution, 518 patients with obstructive CRC whose proximal colon could not be examined by colonoscopy and who underwent preoperative FDG PET/CT were eligible for this study. Of these, final analyses were performed in 345 patients who had reference standards for the proximal colon, which were a surgical colectomy specimen and/or postsurgical colonoscopy. The per-patient and per-lesion performances of FDG PET/CT for synchronous CRC diagnosis were determined. Results Of 345 patients, 14 (4.1%) had 14 proximal synchronous CRCs. Thirty-four patients showed 39 areas of abnormal FDG uptake on PET/CT in the colon proximal to the obstructive CRC. PET/CT detected all of the 14 proximal synchronous CRCs. The per-patient PET/CT sensitivity, specificity, positive predictive value, and negative predictive value for proximal synchronous CRC were 100%, 93.9%, 41.2%, and 100%, respectively. Per-lesion values were 100%, 92.6%, 35.9%, and 100%, respectively. The per-lesion sensitivity and negative predictive value of PET/CT for advanced adenoma were 45.5% and 92.7%, respectively. Conclusions The FDG PET/CT shows a high sensitivity and negative predictive value for the detection of proximal synchronous CRC in patients with obstructive CRC, enabling negative findings in the proximal colon on PET/CT to definitively exclude proximal synchronous CRC. Preoperative PET/CT recommended to determine the proper surgical plan in patients with obstructive CRC. [ABSTRACT FROM AUTHOR]

Serrated polyps have long been thought to lack malignant potential in the human colorectum. However, identification of the serrated pathway to colorectal cancer based on molecular biology has improved our understanding of the pathogenesis of colorectal cancers. Accordingly, serrated polyps such as traditional serrated adenoma and sessile serrated adenoma/polyps (SSA/P) are now considered to be precursor lesions of the serrated pathway. Recently, serrated polyps were classified into three subtypes, consisting of hyperplastic polyp, SSA/P, and traditional serrated adenoma, according to the World Health Organization classification. It has been suggested that SSA/P in the proximal colon are a precursor lesion of pathogenesis of colorectal cancer and are characterized by BRAF mutation and a CpG island methylator phenotype with or without microsatellite instability. However, SSA/P is more challenging to detect by colonoscopy and is likely to account for some interval cancers, particularly in the proximal colon because it presents flat or sessile, isochroous appearance, and occasionally has a mucous cap. Furthermore, the possibility has been raised that pathologists misclassify SSA/P as hyperplastic polyp. It is important for gastroenterologists to recognize the endoscopic features of serrated polyps to facilitate their detection and removal and also to establish postpolypectomy surveillance guidelines. In this review, we discuss the recent classification of serrated polyps; the molecular characteristics of the serrated pathway; appropriate diagnostic methods using endoscopy, including a new image-enhanced endoscopic technique; and management of these lesions. [ABSTRACT FROM AUTHOR]

Purpose: To describe a patient with diplopia who was diagnosed with Turcot syndrome. Methods: A 10-year-old boy presented with a history of left-sided sixth and seventh nerve palsy. He underwent imaging of the brain and colon, a full ophthalmological and genetic work-up. Results: A 10-year-old boy was referred with combined left-sided sixth and seventh nerve palsy since 1 month without symptoms of raised intracranial pressure. BCVA was 6/6 in both eyes. Fundoscopy revealed bilateral, multiple, oval pigmented ocular fundus lesions (POFLs) in the 4 quadrants. These POFLs, together with the cranial nerve palsies raised the suspicion of Turcot syndrome, a familial neoplasia syndrome characterized by familial colorectal cancer and tumours of the central nervous system. Urgent MRI scan of the brain and stereotactic biopsy showed a primitive neuroectodermal tumour (PNET) at the pons. Coloscopy revealed multiple polyps. DNA analysis of the APC gene confirmed the clinical diagnosis of Turcot syndrome. The PNET was treated with combined radio- and chemotherapy. The patient underwent a prophylactic total colectomy as virtually all patients develop a carcinoma of the colorectal region if left untreated. Conclusions: Although strabismus is not, diplopia in childhood is rare and seldom innocuous. It requires a prompt and thorough diagnostic evaluation, including thorough, dilated fundoscopy. The presence of POFLs combined with neurological symptoms suggestive of a brain tumour should alert the clinician of the possibility of Turcot syndrome. Recognition of this rare syndrome can lead to earlier diagnosis, which is vital for appropriate surveillance and early surgical intervention of the highly frequent neoplasias in Turcot Syndrome. [ABSTRACT FROM AUTHOR]

Background: Norcantharidin (NCTD) is a Chinese FDA approved, chemically synthesized drug for cancer treatment. The effect of NCTD on signaling proteins of EGFR and c-Met was systematically elucidated in current study.Methods: Two human colon cancer cell lines, HCT116 and HT29, were used as model systems to investigate the anti-cancer molecular mechanism of NCTD. Cell cycle arrest and early/late apoptosis were analyzed by flow cytometry. The levels of EGFR, phospho-EGFR, c-Met, phospho-c-Met and other related proteins were quantified by western blot analysis.Results: NCTD induced cell cycle arrest at G2/M phase in both cell lines. The early and late apoptosis was also observed. Further investigation indicated that NCTD suppressed not only the expression of the total EGFR and the phosphorylated EGFR but also the expression of the total c-Met and the phosphorylated c-Met in colon cancer cells. Moreover, EGFR expression could be mostly restored by co-treatment with MG132, a proteasome inhibitor. In addition, NCTD-induced cell death was comparable to that of the anti-cancer drug gefitinib, a tyrosine kinase inhibitor for EGFR, based on the immunoblot analysis of the expressed proteins after the drug treatment.Conclusions: NCTD might be a useful and inexpensive drug candidate to substitute for gefitinib to serve the treatment needs of cancer patients. [ABSTRACT FROM AUTHOR]

The objective of this review of the literature is to detail the technical challenges associated with D3 lymphadenectomy for right-sided colon cancer, and to examine the terms used throughout the medical literature to describe the central lymph nodes. We conducted a review of the relevant English language literature, using the electronic search of the PubMed/Medline and Google Scholar databases. The medical literature does not indicate a clear limit between the D3 and D2 lymph nodes for right colon cancer. The central lymph nodes are defined as those located within one centimeter from the origin of the colic arteries. The D3 lymphadenectomy includes ligation of the right colon feeding arteries at their emergence from the superior mesenteric artery (SMA), thus allowing appropriate dissection of the central lymph nodes. The lymphadenectomy of the central lymph nodes requires dissection posterior to the superior mesenteric vein (SMV) when colic arteries have a posterior trajectory to this anatomical structure. An oncological resection for the right-sided colon cancer, with transection of feeding vessels at their emergence from the SMA, is technically demanding, especially when ileocolic and right colic arteries have a trajectory posterior to the SMV. [ABSTRACT FROM AUTHOR]

Background Updated practice guidelines on adjuvant chemotherapy for completely resected colon cancer are lacking. In 2008, Cancer Care Ontario's Program in Evidence-Based Care developed a guideline on adjuvant therapy for stages ii and iii colon cancer. With newer regimens being assessed in this patient population and older agents being either abandoned because of non-effectiveness or replaced by agents that are more efficacious, a full update of the original guideline was undertaken. Methods Literature searches (January 1987 to August 2015) of MEDLINE, EMBASE, and the Cochrane Library were conducted; in addition, abstracts from the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress were reviewed (the latter for January 2007 to August 2015). A practice guideline was drafted that was then scrutinized by internal and external reviewers whose comments were incorporated into the final guideline. Results Twenty-six unique reports of eighteen randomized controlled trials and thirteen unique reports of twelve meta-analyses or pooled analyses were included in the evidence base. The 5 recommendations developed included 3 for stage ii colon cancer and 2 for stage iii colon cancer. Conclusions Patients with completely resected stage iii colon cancer should be offered adjuvant 5-fluorouracil (5FU)-based chemotherapy with or without oxaliplatin (based on definitive data for improvements in survival and disease-free survival). Patients with resected stage ii colon cancer without "high-risk" features should not receive adjuvant chemotherapy. For patients with "high-risk" features, 5FU-based chemotherapy with or without oxaliplatin should be offered, although no clinical trials have been conducted to conclusively demonstrate the same benefits seen in stage III colon cancer. [ABSTRACT FROM AUTHOR]

Abstract Turcot syndrome is a rare hereditary syndrome characterized with the clinical association of colorectal polyposis and brain tumors. Usually the time interval between either the colorectal polyposis or brain tumors presentation is about 5 years in most situation. Colorectal cancer is one of the most common cancer in adult, however it is rare to be seen before the age of 20 years, with annual incidence of 1–2 per million in the US, colorectal cancer associated with a predisposing syndrome account for about 3–4%. We report a rare case of Turcot Syndrome presenting with acute abdomen due to complicated adenocarcinomas involving the transverse colon, sigmoid and rectum in 17-year-old patient who had Glioblastoma 13 years prior to it suggesting Turcot Syndrome. [ABSTRACT FROM AUTHOR]