Study of long non-coding RNA Tug 1 expression in Egyptian colorectal adenocarcinoma patients

Purpose: Colorectal cancer (CRC) is one of the most fatal tumors worldwide. In Egypt, most CRC cases occur in individuals > 40 years old. TUG1 has been proved to be disrupted in different malignancies and may have a critical role in tumor progression, invasion, and metastasis. However, its role in CRC has not been adequately studied. Materials / Methods: Quantitative real-time polymerase chain reaction (PCR) was used to evaluate the expression levels of long non-coding RNA (LncRNA) taurine upregulated gene 1 (TUG1), in nonmetastatic and metastatic CRC tissues and adjacent noncancerous tissues as control. Results: LncRNA TUG1 expression was significantly upregulated in both nonmetastatic and metastatic CRC tissues, in comparison with the adjacent noncancerous tissue. It was found that TUG1 could have a possible prognostic role in CRC, by comparing the sensitivity and specificity of TUG1 with those of CEA and CA19-9. Conclusion: The results of the current study suggest that the LncRNA TUG1 participates in the malignant behaviors of CRC cells. (AU)

Role of Autophagy-apoptosis Balance in Colorectal Cancer and Traditional Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

Colorectal cancer （CRC）， a malignant tumor of the digestive system， originates from the colorectal mucosa epithelium and is usually asymptomatic until it progresses to an advanced stage. With high incidence around the globe and the increasingly younger patients， this disease poses a serious threat to the health and lives of the patients. Although the pathogenesis of this disease is not fully understood， it is generally believed that it is associated with autophagy， apoptosis， and inflammation. Autophagy and apoptosis as two types of programmed cell death are subject to complex interactive regulation， and the imbalance between them is closely related to the occurrence， development， and prognosis of a variety of diseases. Studies have shown that autophagy-apoptosis balance plays a key role in CRC. On the one hand， autophagy and apoptosis coordinate with each other to inhibit CRC cell growth. On the other hand， autophagy can antagonize apoptosis to promote CRC cell growth. In clinical practice， surgery is often combined with radiotherapy and chemotherapy to treat CRC， which can control the progression of CRC to a certain extent but has serious adverse effects and poor long-term results. In recent years， traditional Chinese medicine （TCM） has been proved to be effective in the treatment of CRC. Studies have shown that numerous herbal active components can promote CRC cell death by regulating the autophagy-apoptosis balance， thereby blocking the progression of this disease. The process of autophagy-apoptosis balance in regulating cell activities has similar theoretical connotations with the Yin and Yang theory of TCM. Applying TCM in regulating autophagy-apoptosis balance at various stages of CRC has become a frontier， while the comprehensive elaboration remains to be conducted. By reviewing the relevant studies in recent years， this paper introduces the correlation between the Yin and Yang theory and the autophagy-apoptosis balance， the role of autophagy-apoptosis balance in CRC， and the research progress in the application of 27 Chinese herbal active components such as flavonoids， terpenoids， glycosides， and phenols capable of regulating autophagy-apoptosis balance in the treatment of CRC. The active components in Chinese medicines can recover the autophagy-apoptosis balance in CRC by acting on microtuble-associated protein 1 light chain 3（LC3）， Beclin-1， and B-cell lymphoma-2（Bcl-2）to regulate multiple signaling pathways such as protein kinase B（Akt）/mammalian target of rapamycin（mTOR）and reavtive oxygen species（ROS）/ c-Jun N-terminal kinase（JNK）， thus balancing Yin and Yang. This review aims to provide a reference for the treatment of CRC and the development of new drugs.

Pharmacological inhibition of BAP1 recruits HERC2 to competitively dissociate BRCA1-BARD1, suppresses DNA repair and sensitizes CRC to radiotherapy

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.

Serum long-noncoding RNA H19 and beta-catenin as biomarkers for early diagnosis of colorectal cancer in egyptian patients: a case control study

Colorectal cancer (CRC) is the third most prevalent cancer and the second most common cause of cancer death; however, its early detection can improve the survival. Colonic polyps are considered one of the CRC's major risk factors. Throughout many biological processes and malignancies, the non-coding RNAs have essential functions. Certain long noncoding RNAs (lncRNAs), including H19, were supposed to be CRC possible biomarkers. Also, H19 has been reported to play a role in regulating the activity of beta-catenin, a protein that regulates cell-to-cell adhesion, as well as gene transcription. The current work aimed to investigate the potential significance of LncRNA H19 relative serum expression level by quantitative polymerase chain reaction (q-PCR) and beta-catenin by enzyme-linked immunosorbent assay (ELISA) as noninvasive biomarkers to discriminate between colorectal cancer and colonic polyps. The statistical analysis of the studied factors revealed that the serum expression of H19 and beta-catenin in cancer cases were substantially greater than colonic polyp cases and normal control. Conclusion: The relative expressions of H19 and beta-catenin in the serum can significantly discriminate patients with CRC from those with polyp and normal controls, which could help when screening for CRC. (AU)

Evaluation of microsatellite instability in routine examinations of surgical samples

Context: Approximately 20%–30% of colon cancer cases have a hereditary basis. The genetic defect may involve mismatch repair (MMR) genes, which results in microsatellite instability (MSI). MMR-deficient colorectal cancer may occur due to germline mutation (Lynch syndrome) or be a sporadic one. A tumor's histological features, supported by a panel of immunohistochemistry stains, enables pathologists to assess the MMR status, which in turn has beneficial effects on clinical management. Aims: We aimed to show the relations between histopathological features identified during routine examinations and MMR genes' mutations. Methods and Material: We reviewed retrospectively the material of the Department of Pathology fulfilling the revised Bethesda Guidelines. Statistical Analysis Used: We used Chi-square test, Spearman test, and epidemiological analysis. Results: For the PMS2 gene, the positive predictive value (PPV) indicates that 91% of cases neither present any histological lesions nor have genetic abnormalities. The negative predictive value (NPV) indicates that only 50% of cases have both histological and genetic changes. For the MSH6 gene, the PPV indicates that 85% of tumors without specific histological features do not have genetic abnormalities. Conclusions: We advise universal staining for MLH1, MSH2, MSH6, and PMS2 in every newly diagnosed colon cancer, but due to costly analyses we suggest a protocol for the selection of cases for MMR examinations.

Peroxidase from foxtail millet bran exerts anti-colorectal cancer activity via targeting cell-surface GRP78 to inactivate STAT3 pathway

Molecular targeted therapy has become an emerging promising strategy in cancer treatment, and screening the agents targeting at cancer cell specific targets is very desirable for cancer treatment. Our previous study firstly found that a secretory peroxidase of class III derived from foxtail millet bran (FMBP) exhibited excellent targeting anti-colorectal cancer (CRC) activity in vivo and in vitro, whereas its underlying target remains unclear. The highlight of present study focuses on the finding that cell surface glucose-regulated protein 78 (csGRP78) abnormally located on CRC is positively correlated with the anti-CRC effects of FMBP, indicating it serves as a potential target of FMBP against CRC. Further, we demonstrated that the combination of FMBP with the nucleotide binding domain (NBD) of csGRP78 interfered with the downstream activation of signal transducer and activator of transcription 3 (STAT3) in CRC cells, thus promoting the intracellular accumulation of reactive oxygen species (ROS) and cell grown inhibition. These phenomena were further confirmed in nude mice tumor model. Collectively, our study highlights csGRP78 acts as an underlying target of FMBP against CRC, uncovering the clinical potential of FMBP as a targeted agent for CRC in the future.

A cyclodextrin-based nanoformulation achieves co-delivery of ginsenoside Rg3 and quercetin for chemo-immunotherapy in colorectal cancer

The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety of cancers, the efficacy of immune checkpoint inhibitors is still low in colorectal cancer (CRC). This is mainly due to the immunosuppressive feature of the tumor microenvironment (TME). Emerging evidence reveals that certain chemotherapeutic drugs induce immunogenic cell death (ICD), demonstrating great potential for remodeling the immunosuppressive TME. In this study, the potential of ginsenoside Rg3 (Rg3) as an ICD inducer against CRC cells was confirmed using in vitro and in vivo experimental approaches. The ICD efficacy of Rg3 could be significantly enhanced by quercetin (QTN) that elicited reactive oxygen species (ROS). To ameliorate in vivo delivery barriers associated with chemotherapeutic drugs, a folate (FA)-targeted polyethylene glycol (PEG)-modified amphiphilic cyclodextrin nanoparticle (NP) was developed for co-encapsulation of Rg3 and QTN. The resultant nanoformulation (CD-PEG-FA.Rg3.QTN) significantly prolonged blood circulation and enhanced tumor targeting in an orthotopic CRC mouse model, resulting in the conversion of immunosuppressive TME. Furthermore, the CD-PEG-FA.Rg3.QTN achieved significantly longer survival of animals in combination with Anti-PD-L1. The study provides a promising strategy for the treatment of CRC.

Allosteric inhibition reveals SHP2-mediated tumor immunosuppression in colon cancer by single-cell transcriptomics

Colorectal cancer (CRC), a malignant tumor worldwide consists of microsatellite instability (MSI) and stable (MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing was performed to explore the role of SHP2 in all cell types of tumor microenvironment (TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68+ macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively, our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy.

Efficacy and Mechanism of Shenbai Jiedu Prescription Against Proliferation of HCT116 Cells / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism by which Shenbai Jiedu prescription （SBJDF） inhibits the proliferation of colorectal cancer （CRC） HCT116 cells. MethodAfter 48 h treatment of HCT116 cells with SBJDF （0， 0.25， 0.5， 1， 2， 4 g·L-1）， the viability of HCT116 cells were determined by methyl thiazolyl tetrazolium （MTT） colorimetry. Following the classification of cells into blank control group and SBJDF （1， 2， 4 g·L-1） groups， the effect of SBJDF on HCT116 cell morphology was observed under an inverted microscope. The effects of SBJDF on the proliferation of HCT116 cells and mitochondrial membrane potential （Δψm） were detected by colony formation assay and JC-1 probe， respectively. The flow cytometry was then performed for determining cell cycle distribution and apoptosis. The effects of SBJDF on cell cycle-， apoptosis-， and nuclear factor kappa-B （NF-κB） signaling pathway-related proteins were determined by Western blot. ResultSBJDF effectively inhibited the vitality of HCT116 cells and changed their morphology in a concentration-dependent manner. Compared with the blank control group， SBJDF at 1， 2， 4 g·L-1 significantly reduced cell colony formation （P<0.05， P<0.01），and SBJDF at 2 and 4 g·L-1 arrested the HCT116 cell cycle at G0/G1 phase （P<0.05， P<0.01）. Compared with the blank control group， SBJDF at 1， 2， 4 g·L-1 remarkably down-regulated the protein expression of CyclinD1 （P<0.05， P<0.01）. SBJDF at 2 and 4 g·L-1 lowered the CyclinA2 and cyclin-dependent kinase 4 （CDK4） （P<0.05， P<0.01）. SBJDF at 4 g·L-1 reduced the cyclin-dependent kinase 1 （CDK1） （P<0.01）. Compared with the blank control group， SBJDF at 2 and 4 g·L-1 induced HCT116 cell apoptosis， down-regulated the protein expression of anti-apoptosis-related proteins Bcl-2 and Bcl-xl as well as the NF-κB signaling pathway-related proteins IκB kinase α （IKKα），inhibitor α of NF-κB （IκBα），and phospho-NF-κB p65 （p-p65） （P<0.05， P<0.01）， and diminished the mitochondrial membrane potential of HCT116 cells. ConclusionSBJDF inhibits the proliferation of HCT116 cells， which may be related to its inhibition of the activation of NF-κB signaling pathway and the induction of cell cycle arrest and apoptosis.

CXCL8 Promotes M2 Macrophage Chemotaxis and Infiltration in Colorectal Cancer Microenvironment / 中国生物化学与分子生物学报

CXC chemokine ligand 8 (CXCL8) is highly expressed in many human tumors including colorectal cancer, and it can promote the malignant progression of tumors. It was reported that M2 macrophages were abundant in colorectal cancer microenvironment, but whether CXCL8 affects the infiltration of M2 macrophages and its potential mechanism are not yet clear. The study aimed to investigate the effect of CXCL8 on M2 macrophage infiltration and chemotaxis in the colorectal cancer. Firstly, we analyzed the CXCL8 expression and immune cell infiltration in human colorectal cancer tissues from TCGA RNA-seq data. The expression of CXCL8 was verified by immunohistochemistry in tissues obtained from Shanxi Provincial Cancer Hospital. Then, Western blot and qRT-PCR were employed to detect CXCL8 expression in five colorectal cancer cell lines. THP-1 cells were allowed to differentiate into M2 macrophages via the phorbol myristate acetate (PMA) and IL-4 treatment, followed by detection of the chemotaxis of M2 macrophages towards HCT116, SW480 and CXCL8-HCT116, CXCL8-SW480 cell lines. HCT116 and SW480 cells were treated with interleukin 1β (IL-1β) to detect the expression of CXCL8, and co-cultured with M2 macrophages to analyze the chemotactic activity. The results revealed that the expression of CXCL8 was increased in pairs of CRC tissues versus normal adjacent tissues, and there were more M2 macrophage infiltration in cancer tissues with high expression of CXCL8. The mRNA and protein expression of CXCL8 in HCT116 and SW480 were increased after the IL-1β treatment (P < 0. 05). We confirmed that CXCL8 is a chemotactic factor for M2 macrophages by transwell assays (P<0. 05). In conclusion, CXCL8 in colorectal cancer cells can be induced by IL-1β in colorectal cancer cells and the upregulation of CXCL8 can promote the chemotaxis of M2 macrophages. The massive infiltration of M2 macrophages in colorectal cancer microenvironment may be related with the increased expression of CXCL8.

Siglec-15 Promotes the Proliferation and Migration of Colorectal Cancer Cells and Inhibits the Infiltration of CD4 / 中国生物化学与分子生物学报

Sialic acid binding immunoglobulin type lectin-15 (Siglec-15), one of the Siglec gene family members, is a new immunosuppressive molecule. Siglec-15 is highly expressed in a variety of human tumor cells and tumor-associated macrophages, but the biological function of Siglec-15 in colorectal cancer (CRC) and its effect on the tumor immune microenvironment remains poorly understood. This study aimed to investigate the effects of aberrant expression of Siglec-15 on the biological behaviors of CRC cells and the infiltration of CD4

Detección de mutaciones del Gen KRAS en pacientes paraguayos con cáncer colorrectal / Detection of KRAS Gene mutations in paraguayan patients with colorectal cancer

El estado mutacional del KRAS ha sido considerado como biomarcador para tratamientos biológicos tras varios ensayos clínicos realizados en pacientes con cáncer colorrectal metastásico. Reportes recientes indican que las frecuencias de mutación del gen KRAS en pacientes con CCR de Asia, Europa y Latinoamérica están entre el 24%, 36% y 40%, respectivamente. Paraguay no cuenta con este tipo de informes, a pesar de registrar anualmente en promedio 75 nuevos casos de pacientes diagnosticados con CCR sólo en el Servicio de Cirugía General del Hospital Central del Instituto de Previsión Social (IPS). El presente trabajo ha implementado este análisis de rutina, prerrequisito obligatorio para la administración de fármacos basados en anticuerpos terapéuticos, y revelado una frecuencia de mutación del gen KRAS del 34% en pacientes paraguayos con CCR que acuden a los Servicios del Hospital Central del IPS

The mutational status of the KRAS has been consider as a biomarker for biological treatments after several clinical trials carried out in patient with metastatic colorectal cancer. Recent reports indicate that the KRAS gene mutation frequencies in CRC patients from Asia, Europe, and Latin America are between 24%, 36%, and 40%, respectively. Paraguay does not have this kind of reports, despite registering an average of 75 new cases of patients diagnosed with CRC per year only in the General Surgery Service of the "Central Hospital - Instituto de Prevision Social (IPS)". The present work has implemented this routine analysis, a mandatory prerequisite for the administration of drugs based on therapeutic antibodies and revealed a KRAS gene mutation frequency of 34% in Paraguayan patients with CRC who attend the IPS Central Hospital Services

Expression of TAGLN in colorectal cancer tissues and its effect on malignant biological behaviors of SW480 cells / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the expression of transgelin (TAGLN) in colorectal cancer (CRC) tissues and its effect on the proliferation, migration and invasion of CRC SW480 cells. Methods: Surgically resected CRC tissues and corresponding para-cancerous tissues of 97 CRC patients from May 2015 to August 2016 in the Affiliated Tumor Hospital of Zhengzhou University were collected; In addition, CRC cell lines SW620, SW480, HCT116 and normal colorectal mucosal cell line FHC were also collected for this study. Immunohistochemical staining was used to detect the expression of TAGLN in CRC tissues, and the correlation between TAGLN and patients’ clinicopathological features was analyzed. Quantitative Real-time quantitative polymerase chain reaction (qPCR) and Western blotting (WB) were used to detect the mRNA and protein expressions of TAGLN in CRC cell lines. si-TAGLN and si-Ctrl were respectively transfected into SW480 cells by liposome transfection method. The effects of silencing TAGLN on the proliferation, migration and invasion of SW480 cells were detected by CCK-8, Wound-healing assay and Transwell assay, respectively; and the expression of EMT-related proteins E-cadherin, N-cadherin and vimentin were detected by WB. Results: The positive expression rate of TAGLN in CRC tissues was significantly higher than that in para-cancerous tissues (P<0.01), and TAGLN expression was correlated with TNM stage, degree of tumor differentiation and lymph node metastasis in CRC patients (P<0.05 or P<0.01). The mRNA and protein expression levels of TAGLN in SW480 cells were significantly higher than those in FHC cells (all P<0.01). After TAGLN silence, the proliferation, invasion and migration ability of SW480 cells were significantly reduced (all P<0.01), the expression level of E-cadherin in SW480 cells was increased, while the expression levels of N-cadherin and vimentin were decreased (all P<0.01). Conclusion: TAGLN is highly expressed in CRC tissues and cells. Silencing TAGLN can inhibit the proliferation, invasion and migration of CRC cells, suggesting that TAGLN plays an important role in the occurrence and development of CRC.

Targeting BMI-1-mediated epithelial-mesenchymal transition to inhibit colorectal cancer liver metastasis

Liver is the most common metastatic site for colorectal cancer (CRC), there is no satisfied approach to treat CRC liver metastasis (CRCLM). Here, we investigated the role of a polycomb protein BMI-1 in CRCLM. Immunohistochemical analysis showed that BMI-1 expression in liver metastases was upregulated and associated with T4 stage, invasion depth and right-sided primary tumor. Knockdown

High expression of FABP4 in colorectal cancer and its clinical significance / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

OBJECTIVES@#To investigate the relationship between the fatty acid-binding protein 4 (FABP4) and colorectal cancer (CRC).@*METHODS@#Using an enzyme-linked immunosorbent assay (ELISA), we measured the expression of FABP4 in plasma of 50 patients who underwent surgery for CRC from October 2017 to May 2018 and 50 healthy controls. The content of the visceral fat area (VFA) as seen with abdominal computed tomography (CT) scanning was measured by ImageJ software. The expression levels of FABP4, E-cadherin, and Snail proteins in CRC and adjacent tissues were determined by immunohistochemistry.@*RESULTS@#The mean concentration of plasma FABP4 of CRC patients was higher than that of the control group (22.46 vs. 9.82 ng/mL; @*CONCLUSIONS@#High LPA and VFA were risk factors for increased plasma FABP4 in CRC patients. FABP4 protein was highly expressed in CRC tissues and associated with TNM stage, differentiation, and lymph node metastasis of CRC. The level of FABP4 in CRC tissue was correlated with E-cadherin and Snail expression, suggesting that FABP4 may promote CRC progression related to epithelial-mesenchymal transition (EMT).

Effects of FBXW7α on Expression and Localization of Heat Shock Transcription Factor 1 in Colorectal Cancer Cells / 肿瘤防治研究

Objective To investigate the effect of FBXW7 on the expression and localization of HSF1 in colorectal cancer cells. Methods The expression levels of HSF1 and pHSF1Ser326 protein in FBXW7 deletion (KO) and wild-type (WT) FBXW7-expressing counterpart colorectal cancer cells were detected by Western blot. The nucleoprotein expression and localization of pHSF1Ser326 in heat-shocked or recovery stage cells were observed by Western blot and immunofluorescence method. Results The HSF1 expression level in DLD1 cells transfected with FBXW7α was decreased significantly (P < 0.01). The expression levels of HSF1 and pHSF1Ser326 protein in FBXW7 KO cells were higher than those in WT cells (all P < 0.05). HSF1 and pHSF1Ser326 in FBXW7 KO cells were mainly expressed in nucleus and weakly expressed in cytoplasm. After warm stimulation, the expression of HSF1 and pHSF1Ser326 in WT cells recovered to the unstimulated level, while the expression of HSF1 and pHSF1Ser326 in FBXW7 KO cells were higher in the nucleus (all P < 0.01). Conclusion Loss of FBXW7 could affect the nuclear HSF1 recovery after warm stimulation. It may be associated with FBXW7 deletion inhibiting the degradation of nuclear HSF1.

Circular RNA PVT1 Promotes Proliferation and Represses Apoptosis of Colorectal Cancer Cells / 中国生物化学与分子生物学报

Circular RNAs (circRNAs) are a novel class of long-chain non-coding RNAs. Preceding evidence has showed that circRNAs participate in the development and progression of various tumors. In the present study, we investigated the expression of circRNAs in 5 paired colorectal cancer (CRC) tissues and adjacent normal tissues with circRNA high-throughput sequencing. Totally 477 differentially expressed circRNAs were identified between CRC tissues and non-cancerous matched tissues, which included 252 significantly overexpressed circRNAs and 225 downregulated circRNAs. CircRNA plasmacytoma variant translocation 1 (circPVT1), the most up-regulated expression circRNA, was further confirmed by qRT-PCR in 150 colorectal cancer tissues and matched normal mucosae. Our data revealed that circPVT1 showed a significant up-regulation trend in CRC tissues compared with matched normal mucosae. Similarly, compared with normal colorectal mucosa cells, the expression of circPVT1 in colorectal cancer cell lines was significantly up-regulated (P<0. 05). Functionally, silence with siRNA or overexpression of circPVT1 in colorectal cancer cells was applied to determine the biological functions of circPVT1, including cell proliferation, apoptosis, and cell cycle, etc. The results show that circPVT1 expression significantly attenuated apoptosis, induced replication and promoted proliferation of colorectal cancer cells in vitro. In summary, our findings indicate that circPVT1 plays an oncogenic role in CRC and might be a potential novel target for CRC therapy.

Familial Adenomatous Polyposis Coli in East Africa: A Case Report and Review of the Literature

Introduction: Familial adenomatous polyposis (FAP) is a rare diagnosis in East Africa. The author reports a case of a 21 year old gentleman presenting with occasional passage of blood stained stool, and found to have familial adenomatous polyposis coli. This is followed by a literature review on the pathogenesis, clinical features and treatment options of FAP in East Africa.Presentation of Case: This patient presented with a strong family history of familial adenomatous polyposis, blood stained stool and a rectal mass. A total proctocolectomy and ileoanal anastomosis was carried out. The postoperative course of this patient was uneventful.Discussion: The typical gross pathological and histological features of familial adenomatous polyposis and rectal adenocarcinoma were seen on the resected colorectal specimen. In addition this study reviews the literature regarding the clinical presentation, pathological characteristics and treatment options of familial adenomatous polyposis coli.Conclusion: FAP should always be considered in a young patient presenting with a strong family history of CRC. Colonoscopy should be performed on these patients with early symptoms and those patients with a strong family history of FAP. In East Africa, the creation of a permanent stoma is unacceptable and therefore a proctocolectomy and Brooke ileostomy will not be a desirable option in a young patient in this part of the world

Mucinous Adenocarcinoma of the Colon in Uganda: A Case Report and Literature Review

Introduction:In Uganda, the Kampala Cancer Registry has reported a steady increase in the incidence of colorectal carcinoma(CRC) over the last few decades. The author reports a case of a 25 year old gentlemanpresenting with bowel obstruction and found to have mucinous adenocarcinoma of the colon. This is followed by a literature review of the clinical and pathological characteristics of young age sporadic colorectal carcinoma (YSCC) and hereditary nonpolyposis colorectal carcinoma (HNPCC).Presentation of Case:This patient presented with a family history of colorectal carcinoma (CRC) and with bowel obstruction. An emergency laparotomy involving a right hemicolectomy was carried out. The postoperative course of this patient was uneventful. Discussion:The typical histological features of mucinous adenocarcinoma of the colon were seen on the resected colon specimen. In addition this study reviews the literature regarding the clinical presentation, pathological characteristics, histology and prognosis of mucinous and medullary carcinoma of the colon.Conclusions:Mucinous adenocarcinoma happens to be the most common histological type of colorectal carcinoma in young adults. In Uganda, low risk young patients withsymptoms should be screened for colorectal lesions. A high index of suspicion should therefore be taken in the diagnosis of colorectal malignancy in these patients

Colorectal Adenocarcinoma in East Africa: A Narrative Literature Review

This paper is a review of work done on colorectal adenocarcinomain East Africa showing geographic spread, age and sex ratios, clinical presentation, management and predominant histopathology. A steady increased incidence of CRC in East African countries is currently being documented however this is associated with a higher CRC-associated morbidity and mortality. Whilst the male: Female ratio varies between 1.2:1 to 1.88:1, up to 38% of CRC diagnosis are in patients younger than 40 years, in contrast to only 1.9% of CRC patients in Western developed countries such as the USA. Generally rectal carcinoma is more common than colon carcinoma and abdomino-perineal resections are commonly performed in up to between 54% -71% due to the advanced stage of presentation of rectal tumours in East Africa. The late stage presentationand delayed effective treatment in East Africa may result in a higher morbidity in CRC patients. Interestingly there is a significant incidence of mucinous adenocarcinoma sub-groups compared to Western developed countries which carry a poor prognosis. A significant proportion of CRC patients have been found to have histological and demographic features which suggest that MSI-tumours and these tumours are more common in younger patients. However only a few authors have looked at the possibility of mismatch repair mutations in the genetic aetiopathogenesis of colorectal adenocarcinoma in East Africa.