Publications by authors named "Hassan Ashktorab"

151 Publications

MiRNA-20b/SUFU/Wnt axis accelerates gastric cancer cell proliferation, migration and EMT.

Heliyon 2021 Apr 12;7(4):e06695. Epub 2021 Apr 12.

Guangdong Key Laboratory for Genome Stability & Disease Prevention, Department of Pathology, Shenzhen University School of Medicine, Shenzhen, Guangdong 518060, China.

Previous research has found that miRNA-20b is highly expressed in gastric cancer (GC), however, its function and underlying mechanism are not clear. Wnt signaling pathway, implicated in tumorigeneisis, is activated in more than 30% of GC. We would like to characterize the biological behavior of miRNA-20b in terms of modulating Wnt/β-catenin signaling and EMT. We showed that miRNA-20b inhibitors suppressed Topflash/Fopflash dependent luciferase activity and the β-catenin nuclear translocation, resulting in inhibition of Wnt pathway activity and EMT. SUFU, negatively regulating Wnt and Hedgehog signaling pathway, was proved to be targeted by miRNA-20b. Moreover, additional knockdown of SUFU alleviated the inhibitory effect on Wnt pathway activity, EMT, cell proliferation/migration and colony formation caused by miRNA-20b inhibition. In summary, miRNA-20b is an oncogenic miRNA and promoted cell proliferation, migration and EMT in GC partially by activating Wnt pathway via targeting SUFU.
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http://dx.doi.org/10.1016/j.heliyon.2021.e06695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065298PMC
April 2021

Blood-based liquid biopsies: A non-invasive and cost-effective tool for improved risk assessment and identification of lymph node metastasis in patients with submucosal T1 colorectal cancer.

Gastroenterology 2021 Apr 22. Epub 2021 Apr 22.

Howard University College of Medicine, Cancer Center and Pathology Department, Washington DC 20059.

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http://dx.doi.org/10.1053/j.gastro.2021.04.038DOI Listing
April 2021

Dual activation of Hedgehog and Wnt/β-catenin signaling pathway caused by downregulation of SUFU targeted by miRNA-150 in human gastric cancer.

Aging (Albany NY) 2021 Apr 12;13(7):10749-10769. Epub 2021 Apr 12.

Guangdong Key Laboratory for Genome Stability and Disease Prevention, Department of Pathology, Shenzhen University School of Medicine, Shenzhen 518060, Guangdong, P.R. China.

Mounting evidence has shown that miRNA-150 expression is upregulated in gastric cancer (GC) and is associated with gastric carcinogenesis, but the underlying oncogenic mechanism remains elusive. Here, we discovered that miRNA-150 targets the tumor suppressor SUFU to promote cell proliferation, migration, and the epithelial-mesenchymal transition (EMT) via the dual activation of Hedgehog (Hh) and Wnt signaling. MiRNA-150 was highly expressed in GC tissues and cell lines, and the level of this miRNA was negatively related to that of SUFU. In addition, both the miRNA-150 and SUFU levels were associated with tumor differentiation. Furthermore, miRNA-150 activated GC cell proliferation and migration . We found that miRNA-150 inhibitors repressed not only Wnt signaling by promoting cytoplasmic β-catenin localization, but also repressed Hh signaling and EMT. MiRNA-150 inhibition also resulted in significant tumor volume reductions , suggesting the potential application of miRNA-150 inhibitors in GC therapy. The expression of genes downstream of Hh and Wnt signaling was also reduced in tumors treated with miRNA-150 inhibitors. Notably, anti-SUFU siRNAs rescued the inhibitory effects of miRNA-150 inhibitors on Wnt signaling, Hh activation, EMT, cell proliferation, cell migration, and colony formation. Taken together, these findings indicate that miRNA-150 is oncogenic and promotes GC cell proliferation, migration, and EMT by activating Wnt and Hh signaling via the suppression of SUFU expression.
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http://dx.doi.org/10.18632/aging.202895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064165PMC
April 2021

Trends in the Incidence of Hepatocellular Carcinoma in Washington DC: A Single Institutional Cohort Study (1959-2013).

J Natl Med Assoc 2021 Feb 26. Epub 2021 Feb 26.

Department of Medicine and Cancer Center, Howard University College of Medicine, Washington, DC, USA.

The African American (AA) community in Washington DC is at an elevated risk for hepatocellular carcinoma (HCC) that has a dismal prognosis. The recent rapid increase in the incidence and diagnosis of HCC and liver metastases (LM) in DC prompted us to evaluate the past six decades of this incidence and some of its underlying causes using a single institutional cohort in a hospital located in the center of the city. Electronic medical and pathology records of 454 liver cancer patients from 1959 to 2013 at Howard University Hospital (HUH) were reviewed. Demographic, clinical and pathology characteristics were examined, and statistical analysis was performed using Wilcoxon rank-sum test. Incidence of HCC rose substantially between 1959 and 2013, increasing eight-fold from 1.05 to 8.0 per 100,000 AAs. The rate of increase in the last decade was highest at 550%. Cases were disproportionately male (67.2%), and median age at diagnosis was 57 years. Towards the last decade, the most common etiology for HCC was nonalcoholic fatty liver disease (NAFLD) followed by NAFLD/HCV combination. Liver cancer was clustered in the eastern region of DC in wards 4, 5, 7, and 8. Cases of liver metastases clinically diagnosed and confirmed by biopsies increased 96.4% from 1959 to 1968 to 2009-2013. This study confirms that HCC incidence has been increasing (initially driven by HCV, and NAFLD in the latter decades) more rapidly in DC than previously believed, highlighting the impact of case definitions especially regarding NAFLD in the context of changing diagnostic approaches including the revised ICD10. The rising burden, disproportionate population distribution, and low survival rate among AAs emphasize the importance of prevention and early detection as a public health imperative.
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http://dx.doi.org/10.1016/j.jnma.2021.02.001DOI Listing
February 2021

Helicobacter pylori-induced gastric cancer is orchestrated by MRCKβ-mediated Siah2 phosphorylation.

J Biomed Sci 2021 Feb 3;28(1):12. Epub 2021 Feb 3.

School of Biological Sciences, National Institute of Science Education and Research (NISER) Bhubaneswar, HBNI, P.O. Bhimpur-Padanpur, Via Jatni, Khurda, 752050, Odisha, India.

Background: Helicobacter pylori-mediated gastric carcinogenesis is initiated by a plethora of signaling events in the infected gastric epithelial cells (GECs). The E3 ubiquitin ligase seven in absentia homolog 2 (Siah2) is induced in GECs in response to H. pylori infection. Posttranslational modifications of Siah2 orchestrate its function as well as stability. The aim of this study was to evaluate Siah2 phosphorylation status under the influence of H. pylori infection and its impact in gastric cancer progression.

Methods: H. pylori-infected various GECs, gastric tissues from H. pylori-infected GC patients and H. felis-infected C57BL/6 mice were evaluated for Siah2 phosphorylation by western blotting or immunofluorescence microscopy. Coimmunoprecipitation assay followed by mass spectrometry were performed to identify the kinases interacting with Siah2. Phosphorylation sites of Siah2 were identified by using various plasmid constructs generated by site-directed mutagenesis. Proteasome inhibitor MG132 was used to investigate proteasome degradation events. The importance of Siah2 phosphorylation on tumorigenicity of infected cells were detected by using phosphorylation-null mutant and wild type Siah2 stably-transfected cells followed by clonogenicity assay, cell proliferation assay, anchorage-independent growth and transwell invasion assay.

Results: Siah2 was phosphorylated in H. pylori-infected GECs as well as in metastatic GC tissues at residues serine (Ser) and threonine (Thr). Phosphorylation of Siah2 was mediated by MRCKβ, a Ser/Thr protein kinase. MRCKβ was consistently expressed in uninfected GECs and noncancer gastric tissues but its level decreased in infected GECs as well as in metastatic tissues which had enhanced Siah2 expression. Infected murine gastric tissues showed similar results. MRCKβ could phosphorylate Siah2 but itself got ubiquitinated from this interaction leading to the proteasomal degradation of MRCKβ and use of proteasomal inhibitor MG132 could rescue MRCKβ from Siah2-mediated degradation. Ser and Thr phosphorylated-Siah2 was more stable and tumorigenic than its non-phosphorylated counterpart as revealed by the proliferation, invasion, migration abilities and anchorage-independent growth of stable-transfected cells.

Conclusions: Increased level of Ser and Thr-phosphorylated-Siah2 and downregulated MRCKβ were prominent histological characteristics of Helicobacter-infected gastric epithelium and metastatic human GC. MRCKβ-dependent Siah2 phosphorylation stabilized Siah2 which promoted anchorage-independent survival and proliferative potential of GECs. Phospho-null mutants of Siah2 (S6A and T279A) showed abated tumorigenicity.
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http://dx.doi.org/10.1186/s12929-021-00710-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856738PMC
February 2021

Association of Colonic Diverticula with Colorectal Adenomas and Cancer.

Medicina (Kaunas) 2021 Jan 25;57(2). Epub 2021 Jan 25.

Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.

Conflicting evidence is reported regarding any association between colonic diverticula with colorectal adenomas or cancer. The present study aimed to evaluate, in a cohort of Caucasian patients, the association between colonic diverticula and colorectal polyps and cancer. All consecutive patients undergoing colonoscopy at our institution were included in the study. The presence and location of diverticula, polyps, and cancers were recorded. Histologically, polyps were classified as adenoma (with low or high dysplasia), hyperplastic, or inflammatory. The relative risk of the association of polyps and cancer with diverticula was assessed. Multiple logistic regression analyses, including age, sex, family history for colorectal cancer (CRC), and family history for diverticula, were carried out. During the study period, 1490 patients were enrolled; 37.2% ( = 555) showed colonic diverticula or polyps or CRC (308 males, mean age 66 years). Particularly, 12.3% ( = 183) patients presented only diverticula, 13.7% ( = 204) only polyps or cancer, 11.3% ( = 168) both diseases, and 62.7% ( = 935) neither diverticula nor polyps and cancer. A total of 38 patients presented colorectal cancer, 17 of which had also diverticula. A significant increase in relative risk (RR 2.81, 95% CI 2.27-3.47, < 0.0001) of colorectal adenoma and cancer in patients with colonic diverticula was found. At multivariate analysis, only diverticula resulted to be significantly associated with colorectal adenomas and cancer (Odds Ratio, OR 3.86, 95% CI 2.90-5.14, < 0.0001). A significant association of colonic diverticula with colorectal adenoma or cancer was found. This implies that patients with colonic diverticula require a vigilant follow-up procedure for the prevention of colorectal cancer from those applicable to the general population.
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http://dx.doi.org/10.3390/medicina57020108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910864PMC
January 2021

A Comprehensive Analysis of COVID-19 Impact in Latin America.

Res Sq 2021 Jan 8. Epub 2021 Jan 8.

: Latin America has now become the epicenter of the global coronavirus disease 2019 (COVID-19) pandemic. In the ongoing COVID -19 pandemic, a profound burden of SARS-COV-2 infection has been reported in Latin America. In the present study, we aim to determine the profiles that are associated with this disease in Latin America. We analyzed symptoms, morbidities and gastrointestinal (GI) manifestations by country. We analyzed data from SARS-CoV-2 positive patients evaluated at healthcare centers and hospitals of 8 Latin American countries including Brazil, Peru, Mexico, Argentina, Colombia, Venezuela, Ecuador, and Bolivia between March 1 and July 30, 2020. These countries consist of a total population that exceeds 519 million. Demographics, comorbidities and clinical symptoms were collected. Statistical descriptive analysis and correlation analyses of symptoms, comorbidities and lethality were performed. A total of 728,282 patients tested positive for COVID-19 across all the 8 Latin American countries. Of these, 52.6% were female. The average age was 48.4 years. Peru had the oldest cohort with 56.8 years old and highest rate of females (56.8%) while Chile had the youngest cohort (39 years old). Venezuela had the highest male prevalence (56.7%). Most common symptoms were cough with 60.1% (Bolivia had the highest rate 78%), fatigue/tiredness with 52.0%, sore throat with 50.3%, and fever with 44.2%. Bolivia had fever as the top symptom (83.3%). GI symptoms including diarrhea (highest in Mexico with 22.9%), nausea, vomiting, and abdominal pain were not associated with higher mortality. Hypertension was among the top (12.1%) comorbidities followed by diabetes with 8.3% and obesity 4.5%. In multivariable analyses, the leading and significant comorbidities were hypertension (r=0.83, p=0.02), diabetes (r=0.91, p=0.01), and obesity (r=0.86, p=0.03). Asthma (r=0.37, p=0.54) and increasing age (0.13 p=0.81) were not independently associated with higher mortality. Lethality was highest in Mexico (16.6%) and lowest in Venezuela (0.9%) among the analyzed cohorts. Nearly, 10.5%-53% of patients with COVID-19 have GI manifestations. Differential clinical symptoms were associated with COVID-19 in Latin America countries. Metabolic syndrome components were the main comorbidities associated with poor outcome. Country-specific management and prevention plans are needed. Country-specific management and prevention plans can be established from this meta-analysis.
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http://dx.doi.org/10.21203/rs.3.rs-141245/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805457PMC
January 2021

Lymphatic metastasis-related TBL1XR1 enhances stemness and metastasis in gastric cancer stem-like cells by activating ERK1/2-SOX2 signaling.

Oncogene 2021 Feb 7;40(5):922-936. Epub 2020 Dec 7.

Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

The poor prognosis of gastric cancer (GC) results largely from metastasis and chemotherapy resistance. Toward novel therapeutic strategies that target or evade these phenomena, we evaluated the function of the transcriptional regulator transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) in GC cells, including stem-like cells. In this study, the correlation of expression of TBL1XR1 and clinical features and GC patients' outcomes was evaluated. Knockdown or exogenous expression of TBL1XR1 was combined with in vitro (2D and 3D cultures) and in vivo (mouse lung and lymphatic metastasis models) assays to evaluate the function of TBL1XR1. TBL1XR1's downstream signaling was delineated by phospho-kinase array and knockdown of candidate mediators. Analysis of clinical data showed that TBL1XR1 overexpression was correlated with worse prognosis. Functional assays showed that TBL1XR1 promoted stemness, epithelial-mesenchymal transition (EMT), and lung and lymphatic metastasis in GC cells. TBL1XR1 activated ERK1/2-Sox2 signaling and was dependent on signaling via PI3K/AKT, in GC stem-like cells distinguished by CD44 expression. Moreover, inhibition of these signaling proteins reversed chemoresistance in in vitro and in vivo models. Taken together, our results indicate that TBL1XR1 promotes stemness and metastasis in GC, making it a potential prognostic indicator. The PI3K/AKT-TBL1XR1-ERK1/2-Sox2 axis may represent a target for the treatment of GC.
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http://dx.doi.org/10.1038/s41388-020-01571-xDOI Listing
February 2021

COVID-19 in Latin America: Symptoms, Morbidities, and Gastrointestinal Manifestations.

Gastroenterology 2021 02 6;160(3):938-940. Epub 2020 Nov 6.

Department of Medicine, Howard University College of Medicine, Washington, District of Columbia; Department of Pathology and Cancer Center, Howard University College of Medicine, Washington, District of Columbia; Department of Biochemistry and Molecular Biology, Howard University College of Medicine, Washington, District of Columbia.

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http://dx.doi.org/10.1053/j.gastro.2020.10.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644436PMC
February 2021

Histone methyltransferase SET8 is regulated by miR-192/215 and induces oncogene-induced senescence via p53-dependent DNA damage in human gastric carcinoma cells.

Cell Death Dis 2020 10 30;11(10):937. Epub 2020 Oct 30.

Guangdong Key Laboratory for Genome Stability & Disease Prevention and Regional Immunity and Diseases, Department of Pathology, Shenzhen University School of Medicine, Shenzhen, Guangdong, 518060, People's Republic of China.

Gastric cancer (GC) is the most common cancer throughout the world. Despite advances of the treatments, detailed oncogenic mechanisms are largely unknown. In our previous study, we investigated microRNA (miR) expression profiles in human GC using miR microarrays. We found miR-192/215 were upregulated in GC tissues. Then gene microarray was implemented to discover the targets of miR-192/215. We compared the expression profile of BGC823 cells transfected with miR-192/215 inhibitors, and HFE145 cells transfected with miR-192/-215 mimics, respectively. SET8 was identified as a proposed target based on the expression change of more than twofold. SET8 belongs to the SET domain-containing methyltransferase family and specifically catalyzes monomethylation of H4K20me. It is involved in diverse functions in tumorigenesis and metastasis. Therefore, we focused on the contributions of miR-192/215/SET8 axis to the development of GC. In this study, we observe that functionally, SET8 regulated by miR-192/215 is involved in GC-related biological activities. SET8 is also found to trigger oncogene-induced senescence (OIS) in GC in vivo and in vitro, which is dependent on the DDR (DNA damage response) and p53. Our findings reveal that SET8 functions as a negative regulator of metastasis via the OIS-signaling pathway. Taken together, we investigated the functional significance, molecular mechanisms, and clinical impact of miR-192/215/SET8/p53 in GC.
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http://dx.doi.org/10.1038/s41419-020-03130-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599338PMC
October 2020

Association of Human Papillomavirus Genotype 16 Lineages With Anal Cancer Histologies Among African Americans.

Gastroenterology 2021 Feb 17;160(3):922-924. Epub 2020 Oct 17.

Departments of Internal Medicine, Surgery, and Pathology, Howard University College of Medicine, Washington DC.

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http://dx.doi.org/10.1053/j.gastro.2020.10.022DOI Listing
February 2021

Association of patients' perception of quality of healthcare received and colorectal cancer screening uptake: An analysis of two national surveys in the United States.

Med Princ Pract 2020 Oct 13. Epub 2020 Oct 13.

Objective: It is unknown whether patients' ratings of the quality of healthcare services they receive truly correlate with the quality of care from their providers. Understanding this association can potentiate improvement in healthcare delivery. We evaluated the association between patients' ratings of the quality of healthcare services received and uptake of colorectal cancer (CRC) screening.

Subject And Methods: We used two iterations of the Health Information National Trends Survey (HINTS) of adults in the United States. HINTS 2007 (4,007 respondents; weighted population=75,397,128) evaluated whether respondents were up-to-date with CRC screening while HINTS 4 cycle 3 (1,562 respondents; weighted population=76,628,000) evaluated whether participants had ever received CRC screening in the past. All included respondents from both surveys were at least 50 years of age, had no history of CRC, and had rated the quality of healthcare services that they had received at their healthcare provider's office in the previous 12 months.

Results: HINTS 2007 data showed that respondents who rated their healthcare as good, or fair/poor were significantly less likely to be up to date with CRC screening compared to those who rated their healthcare as excellent. We found comparable results from analysis of HINTS 4 cycle 3 data with poorer uptake of CRC screening as the healthcare quality ratings of respondents' reduced.

Conclusion: Our study suggested that patients who reported receiving lower quality of healthcare services were less likely to have undergone and be compliant with CRC screening recommendations. It is important to pay close attention to patient feedback surveys in order to improve healthcare delivery.
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http://dx.doi.org/10.1159/000512233DOI Listing
October 2020

SUFU mediates EMT and Wnt/β-catenin signaling pathway activation promoted by miRNA-324-5p in human gastric cancer.

Cell Cycle 2020 10 5;19(20):2720-2733. Epub 2020 Oct 5.

Guangdong Key Laboratory for Genome Stability & Disease Prevention, Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pathology, Shenzhen University School of Medicine , Shenzhen, Guangdong, China.

The poor prognosis of late gastric carcinomas (GC) underscores the necessity to identify novel biomarkers for earlier diagnosis and effective therapeutic targets. MiRNA-324-5p has been shown to be over-expressed in GC, however the biological function of miRNA-324-5p implicated in gastric cancer and its downstream targets were not well understood. Wnt/β-catenin signaling pathway is aberrantly regulated in GC. We sought to explore if miRNA-324-5p promotes oncogenesis through modulating Wnt signaling and EMT. MiRNA-324-5p is highly expressed in GC based on qRT-PCR and TCGA data. In addition, in vitro cell proliferation, cell migration assays and in vivo animal exenograft were executed to show that miRNA-324-5p is an oncogenic miRNA in GC. MiRNA-324-5p activates Wnt signaling and induces EMT in GC. Further, SUFU was identified as a target of miRNA-324-5p confirmed by western blotting and luciferase assays. Spearson analysis and TCGA data indicate that the expression of SUFU is negatively associated with the expression of miRNA-324-5p. Rescue experiments were performed to determine if SUFU mediates the Wnt activation, EMT and oncogenic function of miRNA-324-5p. MiRNA-324-5p inhibitors plus SUFU siRNAs rescue partially the inhibitory effect on Wnt signaling and EMT caused by miRNA-324-5p inhibitors. Finally, the suppression of cell proliferation, migration, and colony formation ability induced by miRNA-324-5p inhibitors is alleviated by addition of SUFU siRNAs. In summary, miRNA-324-5p is overexpressed and exerts cell growth and migration-promoting effects through activating Wnt signaling and EMT by targeting SUFU in GC. It represents a potential miRNA with an oncogenic role in human gastric cancer.
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http://dx.doi.org/10.1080/15384101.2020.1826632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644164PMC
October 2020

Analysis of β-catenin association with obesity in African Americans with premalignant and malignant colorectal lesions.

BMC Gastroenterol 2020 Aug 18;20(1):274. Epub 2020 Aug 18.

Department of Medicine, Department of Pathology and Cancer Center, Howard University College of Medicine, 2041 Georgia Avenue, N.W, Washington, D.C, 20060, USA.

Background: African Americans (AA) are at high risk for Colorectal Cancer (CRC). Studies report a 30-60% increase in CRC risk with physical inactivity, obesity and metabolic syndrome. Activation of the WNT/β-catenin (CTNNB1) signaling pathway plays a critical role in colorectal carcinogenesis. Accumulating evidence also indicates a role of WNT-CTNNB1 signaling in obesity and metabolic diseases.

Aim: To examine the association between obesity, β-Catenin expression and colonic lesions in African Americans.

Methods: We reviewed the pathology records of 152 colorectal specimens from 2010 to 2012 (46 CRCs, 74 advanced adenomas and 32 normal colon tissues). Tissue Microarrays (TMA) were constructed from these samples. Immunohistochemistry (IHC) for CTNNB1 (β-Catenin; clone β-Catenin-1) was performed on the constructed TMAs. The IHC results were evaluated by 2 pathologists and the nuclear intensity staining was scored from 0 to 4. BMI, sex, age, location of the lesion and other demographic data were obtained.

Results: Positive nuclear staining in normal, advanced adenoma and CRC was 0, 24 and 41%, respectively (P < 0.001). CRC was asso ciated with positive status for nuclear CTNNB1 intensity (adjusted OR: 3.40, 95%CI = 1.42-8.15, P = 0.006 for positive nuclear staining) compared to non-CRC samples (Normal or advanced adenoma). Nuclear staining percentage has a fair diagnostic ability for CRC with an AUC of 0.63 (95%CI = 0.55-0.71). Overweight/obese patients (BMI > 25) did not show a significant difference in (p = 0.3) nuclear CTNNB1 staining (17% positive in normal weight vs. 27% positive in overweight/obese). The association between nuclear intensity and CRC was not different between normal and overweight patients (P for interaction = 0.6). The positive nuclear CTNNB1status in CRC stage III and IV (35% of all CRC) was not different from stage I and II (50% vs. 36%, respectively, P = 0.4).

Conclusion: In our study, advanced adenoma and CRC were associated with activation of β-catenin in physically fit, overweight and obese patients. Thus, obesity and WNT/β-Catenin pathway seem to be independent in African American patients. WNT/β-Catenin signaling pathway has a potential to be used as an effector in colon carcinogenic transformation. Whether or not BMI is a modifier of this pathway needs to be investigated further.
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http://dx.doi.org/10.1186/s12876-020-01412-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433356PMC
August 2020

Saffron Crudes and Compounds Restrict MACC1-Dependent Cell Proliferation and Migration of Colorectal Cancer Cells.

Cells 2020 08 3;9(8). Epub 2020 Aug 3.

Experimental and Clinical Research Center, Charité-Universitätsmedizin Berlin, and Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Straße 10, 13125 Berlin, Germany.

The high mortality rate of colorectal cancer (CRC) patients is directly associated with metastatic dissemination. However, therapeutic options specifically for metastasis are still limited. We previously identified Metastasis-Associated in Colon Cancer 1 (MACC1) as a major causal metastasis-inducing gene. Numerous studies confirmed its value as a biomarker for metastasis risk. We investigated the inhibitory impact of saffron on MACC1-induced cancer cell growth and motility. Saffron crudes restricted the proliferation and migration of MACC1-expressing CRC cells in a concentration- and MACC1-dependent manner. Saffron delays cell cycle progression at G2/M-phase and does not induce apoptosis. Rescue experiments showed that these effects are reversible. Analysis of active saffron compounds elucidated that crocin was the main compound that reproduced total saffron crudes effects. We showed the interaction of MACC1 with the cancer stem cell (CSC) marker DCLK1, which contributes to metastasis formation in different tumor entities. Saffron extracts reduced DCLK1 with crocin being responsible for this reduction. Saffron's anti-proliferative and anti-migratory effects in MACC1-expressing cells are mediated by crocin through DCLK1 down-regulation. This research is the first identification of saffron-based compounds restricting cancer cell proliferation and motility progression via the novel target MACC1.
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http://dx.doi.org/10.3390/cells9081829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463853PMC
August 2020

TGR5-HNF4α axis contributes to bile acid-induced gastric intestinal metaplasia markers expression.

Cell Death Discov 2020 6;6:56. Epub 2020 Jul 6.

State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032 China.

Intestinal metaplasia (IM) increases the risk of gastric cancer. Our previous results indicated that bile acids (BAs) reflux promotes gastric IM development through kruppel-like factor 4 (KLF4) and caudal-type homeobox 2 (CDX2) activation. However, the underlying mechanisms remain largely elusive. Herein, we verified that secondary BAs responsive G-protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5) was increased significantly in IM specimens. Moreover, TGR5 contributed to deoxycholic acid (DCA)-induced metaplastic phenotype through positively regulating KLF4 and CDX2 at transcriptional level. Then we employed PCR array and identified hepatocyte nuclear factor 4α (HNF4α) as a candidate mediator. Mechanically, DCA treatment could induce HNF4α expression through TGR5 and following ERK1/2 pathway activation. Furthermore, HNF4α mediated the effects of DCA treatment through directly regulating KLF4 and CDX2. Finally, high TGR5 levels were correlated with high HNF4α, KLF4, and CDX2 levels in IM tissues. These findings highlight the TGR5-ERK1/2-HNF4α axis during IM development in patients with BAs reflux, which may help to understand the mechanism underlying IM development and provide prospective strategies for IM treatment.
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http://dx.doi.org/10.1038/s41420-020-0290-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338499PMC
July 2020

Determination of distinctive hypomethylated genes in African American colorectal neoplastic lesions.

Therap Adv Gastroenterol 2020 27;13:1756284820905482. Epub 2020 May 27.

Department of Pathology, and Medicine, Howard University, 2041 Georgia Avenue NW, Washington, DC 20059, USA.

Background: Few studies have analyzed progressive demethylation in the path to cancer. This is of utmost importance, especially in populations such as African Americans, who display aggressive tumors at diagnosis, and for whom markers of early neoplastic transformation are needed. Here, we determined hypomethylated targets in the path to colorectal cancer (CRC) using Reduced Representation Bisulfite Sequencing (RRBS).

Methods: DNA was extracted from fresh frozen tissues of patients with different colon lesions (normal, tubular adenoma, tubulovillous adenoma, and five cancers). RRBS was performed on these DNA extracts to identify hypomethylated gene targets. Alignment, mapping, and methylation analyses were performed. Pathways affected by the hypomethylated gene targets were determined using Ingenuity Pathway Analysis (IPA).

Results: Pairwise analyses of samples led to the identification of the following novel hypomethylated genes: (Engulfment and cell motility 3), (Solute carrier family 6 member 2), (Synemin), and (Homeobox 2). The promoter was significantly hypomethylated at five CpG sites, at two CpG sites, at one CpG site, and the gene at one CpG site. IPA placed these genes within important carcinogenic pathways.

Conclusions: This work provides insight into the role of hypomethylation in colon carcinogenesis in African Americans. The identified targets affected many important pathways, as demonstrated through IPA. These targets might serve as biomarkers for early diagnosis and potential targets for therapy.
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http://dx.doi.org/10.1177/1756284820905482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273615PMC
May 2020

Inflammatory polyps occur more frequently in inflammatory bowel disease than other colitis patients.

BMC Gastroenterol 2020 Jun 5;20(1):170. Epub 2020 Jun 5.

Gastroenterology division, Stanford University, School of Medicine, Palo Alto, California, USA.

Background: Colitis is generally considered a risk factor for colon neoplasia. However, not all types of colitis seem to have equal neoplastic transformation potential.

Aim: To determine the prevalence of colorectal polyps in a predominantly African American population with inflammatory bowel disease (IBD) and Non-IBD/Non-Infectious Colitis (NIC).

Methods: We retrospectively evaluated medical records of 1060 patients previously identified with colitis at Howard University Hospital, based on ICD-10 code. Among these, 485 patients were included in the study: 70 IBD and 415 NIC based on a thorough review of colonoscopy, pathology and clinical reports. Logistic regression analysis was applied to estimate the risk of polyps in patients with IBD compared to those with NIC after adjusting for age and sex. A subgroup analysis within the IBD group was performed.

Results: Of the 485 patients, 415 were NIC and 70 were IBD. Seventy-three percent of the NIC patients and 81% of the IBD patients were African Americans. Forty six percent of IBD and 41% of NIC cases were male. IBD patients were younger than NIC patients (median age of 38 years vs. 50, P < 0.001). The prevalence of all types of polyps was 15.7 and 8.2% in the IBD and NIC groups, respectively (P = 0.045). Among patients with polyps, the prevalence of inflammatory polyps was higher in the IBD group (55%) compared to the NIC group (12%). After adjusting for age, sex and race, odds ratio of inflammatory polyps in IBD patients was 6.0 (P = 0.016). Adenoma prevalence was 4.3% (3/70) in IBD patients and 3.9% (16/415) in the NIC patients (p = 0.75). The anatomic distribution of lesions and colitis shows that polyps occur predominantly in the colitis field regardless of colitis type. More polyps were present in the ulcerative colitis patients when compared to Crohn's disease patients (27% vs. 5%, P < 0.001) within the IBD group.

Conclusion: Our study shows that inflammatory polyps are more common in IBD patients when compared to NIC patients. Most polyps were in the same location as the colitis.
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http://dx.doi.org/10.1186/s12876-020-01279-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275388PMC
June 2020

Molecular Signatures of MINA53 in Gastric Cancer.

Cancers (Basel) 2020 May 2;12(5). Epub 2020 May 2.

Department of Integrative Biotechnology, Sungkyunkwan University, and Biomedical Institute for Convergence at SKKU (BICS), Suwon 16419, Korea.

The gene and its encoded protein MYC-induced nuclear antigen (MINA53) are associated with multiple cancers. Besides having both an oncogenic and tumor suppressor function, the intricate role of in cancer is complex as it depends on the cancer type. In particular, the functional role of /MINA53 in gastric cancer has been poorly understood. In this study, we have unraveled the molecular signatures and functional roles of /MINA53 in gastric cancer by multiple approaches, i.e., multi-omics bioinformatics study, analysis of human gastric cancer tissues, and studies in vitro using knockdown or overexpression strategies in gastric cancer cell lines. The results indicated that the gene and MINA53 protein are commonly overexpressed in cancer patients. JMJD10/MINA53 is involved in the regulation of proliferation and survival of gastric cancer by controlling cell cycle gene expression. These processes are highly associated with MINA53 enzymatic activity in the regulation of H3K9me3 methylation status and controlling activation of AP-1 signaling pathways. This highlights the oncogenic role of /MINA53 in gastric cancer and opens the opportunity to develop therapeutic targeting of /MINA53 in gastric cancer.
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http://dx.doi.org/10.3390/cancers12051141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281541PMC
May 2020

Comparison of patterns of laxative ingestion to improve bowel preparation for colonoscopy: a pilot randomized clinical trial.

Endosc Int Open 2020 May 17;8(5):E617-E622. Epub 2020 Apr 17.

Georgetown-Howard Universities Center for Clinical and Translations Science, Washington, District of Columbia, United States.

 Negative experiences with bowel preparation are a barrier to uptake of colonoscopy. The aim of this study was to examine the impact of different flavoring of polyethylene glycol (PEG) laxatives on patient satisfaction with and adequacy of bowel preparation during colonoscopy.  This was a single-blind (endoscopist), parallel design, randomized trial (NCT02062112) during which patients scheduled for colonoscopy were assigned to one of three groups: Group 1 (no laxative flavoring, n = 84); Group 2 (flavored entire laxative, n = 90) and Group 3 (tasted PEG with and without flavoring and decided how they want to drink the rest of the laxatives (choice group), n = 82). Patients rated their bowel preparation experience (satisfaction) and endoscopists accessed adequacy of bowel preparation during colonoscopy.  There were no differences in patient ratings across the groups (1, 2 and 3) in taste of the laxatives (  = 0.67), ease of drinking (  = 0.53), and overall experience of bowel preparation process (  = 0.18). However, higher percentage of patients in the choice group would want the same laxative again if they were going to have a repeat colonoscopy in the future (72.5 % vs 81.3 % vs 88.9 %,  = 0.04). Surprisingly, adequacy of bowel preparation was highest among patients who drank their PEG unflavored (89.3 % vs 80 % vs 75.5 %,  = 0.07) and the had highest rates of adenoma detection (40.5 % vs 23.3 vs 39.0,  = 0.03).  There were no differences in overall tolerability of bowel preparation by patterns of flavoring of PEG. Those who drank unflavored PEG were less satisfied but had better clinical outcome, suggesting minimum justification effect in bowel preparation process.
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http://dx.doi.org/10.1055/a-1118-3526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165003PMC
May 2020

Altered ARID1A expression in colorectal cancer.

BMC Cancer 2020 Apr 25;20(1):350. Epub 2020 Apr 25.

Cancer Center and Department of Medicine, Howard University, College of Medicine, 2041 Georgia Avenue, N.W., Washington, D.C., 20060, USA.

Background: ARID1A has been described as a tumor suppressor gene, participating in chromatin re-modeling, epithelial-mesenchymal-transition and many other cellular and molecular processes. It has been cited as a contribute in tumorigenesis. The role of ARID1A in CRC is not yet defined.

Aim: To investigate the role of ARID1A methylation and CNV in its expression in CRC cell lines and to examine the relationship between ARID1A status with survival and clinicopathologic characteristics in patients with CRC.

Methods: We used RT-PCR to determine both CNV and expression of ARID1A from six CRC cell lines. We used MSP to evaluate methylation of ARID1A. IHC was used to assess ARID1A protein expression. We also evaluated MSI and EMAST status in 18 paired CRC and adjacent normal tissues. 5AzadC was used to assess effect of DNA demethylation on ARID1A expression. Statistical analysis was performed to establish correlations between ARID1A expression and other parameters.

Results: Among the 18 CRC tumors studied, 7 (38.8%) and 5 tumors (27.7%) showed no or low ARID1A expression, respectively. We observed no significant difference in ARID1A expression for overall patient survival, and no difference between clinicopathological parameters including MSI and EMAST. However, lymphatic invasion was more pronounced in the low/no ARID1A expression group when compared to moderate and high expression group (33% VS. 16.6% respectively. ARID1A promoter methylation was observed in 4/6 (66%) cell lines and correlated with ARID1A mRNA expression level ranging from very low in SW48, to more pronounced in HCT116 and HT-29/219. Treatment with the methyltransferase inhibitor 5-Azacytidine (5-aza) resulted in a 25.4-fold and 6.1-fold increase in ARID1A mRNA expression in SW48 and SW742 cells, respectively, while there was no change in SW480 and LS180 cells. No ARID1A CNV was observed in the CRC cell lines.

Conclusion: ARID1A expression is downregulated in CRC tissues which correlates with it being a tumor suppressor protein. This finding confirms ARID1A loss of expression in CRC development. Our in-vitro results suggest high methylation status associates with reduced ARID1A expression and contributes to CRC tumorigenesis. However, there was no significant association between ARID1A loss of expression and clinicopathological characteristics. Future in-vivo analysis is warranted to further establish ARID1A role in colorectal neoplastic transformation.
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http://dx.doi.org/10.1186/s12885-020-6706-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183124PMC
April 2020

Uptake and tumor-suppressive pathways of exosome-associated GKN1 protein in gastric epithelial cells.

Gastric Cancer 2020 09 6;23(5):848-862. Epub 2020 Apr 6.

Department of Pathology, Functional RNomics Research Center, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, South Korea.

Background: Gastrokine 1 (GKN1) is a stomach-specific tumor suppressor that is secreted into extracellular space as an exosomal cargo protein. The objective of this study was to investigate the uptake and tumor-suppressive pathways of exosome-associated GKN1 protein in gastric epithelial cells.

Methods: Immunofluorescent and Western blot analysis were used to investigate gastric-specific uptake of HFE-145-derived exosomes. Binding affinity of HFE-145 derived exosomes with integrin proteins was examined using protein microarray chip. Tumor suppressor activities of exosome-carrying GKN1 protein were analyzed using transwell co-culture, MTT assay, BrdU incorporation, immunoprecipitation, and Western blot analysis.

Results: HFE-145-derived exosomes were internalized only into HFE-145 gastric epithelial cells and gastric cancer cells. Gastric-specific uptake of stomach-derived exosomes required integrin α6 and αX proteins. Clathrin and macropinocytosis increased the uptake of exosomes into gastric epithelial cells, whereas caveolin inhibited the uptake of exosomes. Transwell co-culture of AGS cells with HFE-145 cells markedly inhibited viability and proliferation of AGS cells. Following uptake of HFE-145-derived exosomes in recipient cells, GKN1 protein bound to HRas and inhibited the binding of HRas to b-Raf and c-Raf which subsequently downregulated HRas/Raf/MEK/ERK signaling pathways in AGS, MKN1 cells, and MKN1-derived xenograft tumor tissues. In addition, exosomal GKN1 protein suppressed both migration and invasion of gastric cancer cells by inhibiting epithelial-mesenchymal transition.

Conclusions: Gastric-specific uptake of exosomes derived from gastric epithelial cells requires integrin α6 and αX proteins in both gastric epithelial cells and exosomes. Exosomal GKN1 protein inhibits gastric carcinogenesis by downregulating HRas/Raf/MEK/ERK signaling pathways.
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http://dx.doi.org/10.1007/s10120-020-01068-2DOI Listing
September 2020

Factors influencing treatment outcome in hepatitis C virus minority patients at an inner-city hospital: A STROBE-complaint article.

Medicine (Baltimore) 2020 Apr;99(14):e19505

Department of Medicine, Howard University Hospital.

Chronic hepatitis C virus (HCV) infection disproportionately affects African-Americans (AAs) and is a major contributor to liver failure and mortality. Genetic factors may not be the only cause in outcome disparity. We retrospectively investigated whether genetic host factors, viral genotypes, and treatment compliance in AA patients impacted the efficacy and the sustained virological response (SVR) rate of the interferon (IFN)-based treatment regimen. The medical chart review included 76 African-American patients (age ranging from 26 to 76) with varying levels of hepatitis condition. Fifty-seven (75%) of them had a clinically verifiable HCV infection and were followed by a hepatologist for 2 years at Howard University Hospital in Washington, DC. Both comprehensive metabolic profile and complete blood count analyses were performed. Among the 57 patients whose viral and IL28B genotypes were determined, sixty-eight percent (68%) were infected with viral genotype 1 and 71% harbored the CT allele of the IL28B gene. Among the 12 patients who completed treatment with IFN-based dual or triple therapy, 58% had achieved SVR 12 weeks following completion of treatment; 33% had a partial response with under 6000 viral count after 16 weeks of treatment; and there was one patient with viral genotype 1a and CT allele who did not respond to the medications. The results of this study prove that the PEG IFN-based regimen was effective in treating HCV-infected AA patients despite the current availability of new direct-acting antivirals. The major obstacles contributing to a low reduction in HCV infection and outcome in the AA community were avoidance or lack of treatment or compliance; contraindications, medication side effects, non-adherence, and payer eligibility restrictions.
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http://dx.doi.org/10.1097/MD.0000000000019505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220685PMC
April 2020

Expression of Tight Junction Proteins According to Functional Dyspepsia Subtype and Sex.

J Neurogastroenterol Motil 2020 Apr;26(2):248-258

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea.

Background/aims: To determine whether the expression of tight junction proteins (TJPs) differs depending on the subtype of functional dyspepsia (FD) and sex.

Methods: Control (n = 95) and FD (n = 165) groups based on Rome III criteria were prospectively enrolled. Gastric mucosal mRNA expression levels of various TJPs (claudins [CLDN] 1, 2, and 4; zonula occludens-1; occludin [OCLN]) were assessed by reverse transcription polymerase chain reaction. Western blot was performed to determine the levels of various TJPs. infection status was evaluated by histology, rapid urease test, and culture. Questionnaires were analyzed.

Results: In all groups irrespective of , FD group showed significantly higher CLDN2 mRNA levels than control group ( = 0.048). The level of CLDN4 mRNA expression was significantly lower in female FD group than in male FD group ( = 0.018). In uninfected subjects, the level of CLDN1 mRNA expression in female FD group was significantly lower than that of male FD group ( = 0.014). The level of CLDN2 mRNA expression was significantly higher in the male postprandial distress syndrome ( = 0.001) and male epigastric pain syndrome ( = 0.023) groups than in the male control group. In Western blot analysis, the expression of OCLN was significantly elevated 48 hour after the culture with strain 43504.

Conclusions: can affect a variety of TJPs, particularly claudin-4 and occludin. Claudin-2 is thought to be involved in FD irrespective of status, especially in the pathophysiology of male FD.
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http://dx.doi.org/10.5056/jnm19208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176499PMC
April 2020

Histone deacetylase inhibitor pre-treatment enhances the efficacy of DNA-interacting chemotherapeutic drugs in gastric cancer.

World J Gastroenterol 2020 Feb;26(6):598-613

Epigenetics and Chromatin Biology Group, Gupta Laboratory, Cancer Research Institute, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra 410210, India.

Background: The prognosis of gastric cancer continues to remain poor, and epigenetic drugs like histone deacetylase inhibitors (HDACi) have been envisaged as potential therapeutic agents. Nevertheless, clinical trials are facing issues with toxicity and efficacy against solid tumors, which may be partly due to the lack of patient stratification for effective treatments.

Aim: To study the need of patient stratification before HDACi treatment, and the efficacy of pre-treatment of HDACi as a chemotherapeutic drug sensitizer.

Methods: The expression activity of class 1 HDACs and histone acetylation was examined in human gastric cancer cells and tissues. The potential combinatorial regime of HDACi and chemotherapy drugs was defined on the basis of observed drug binding assays, chromatin remodeling and cell death.

Results: In the present study, the data suggest that the differential increase in HDAC activity and the expression of class 1 HDACs are associated with hypo-acetylation of histone proteins in tumors compared to normal adjacent mucosa tissue samples of gastric cancer. The data highlights for the first time that pre-treatment of HDACi results in an increased amount of DNA-bound drugs associated with enhanced histone acetylation, chromatin relaxation and cell cycle arrest. Fraction-affected plots and combination index-based analysis show that pre-HDACi chemo drug combinatorial regimes, including valproic acid with cisplatin or oxaliplatin and trichostatin A with epirubicin, exhibit synergism with maximum cytotoxic potential due to higher cell death at low combined doses in gastric cancer cell lines.

Conclusion: Expression or activity of class 1 HDACs among gastric cancer patients present an effective approach for patient stratification. Furthermore, HDACi therapy in pre-treatment regimes is more effective with chemotherapy drugs, and may aid in predicting individual patient prognosis.
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http://dx.doi.org/10.3748/wjg.v26.i6.598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029347PMC
February 2020

miRNA-192 and -215 activate Wnt/β-catenin signaling pathway in gastric cancer via APC.

J Cell Physiol 2020 09 24;235(9):6218-6229. Epub 2020 Feb 24.

Department of Pathology, Guangdong Key Laboratory for Genome Stability & Disease Prevention, The Shenzhen University School of Medicine, Shenzhen, Guangdong, China.

Although great progress has been made in surgical techniques, traditional radiotherapy, and chemotherapy, gastric cancer (GC) is still the most common malignant tumor and has a high mortality, which highlights the importance of novel diagnostic markers. Emerging studies suggest that different microRNAs (miRNAs) are involved in tumorigenesis of GC. In this study, we found that miRNA-192 and -215 are significantly upregulated in GC and promote cell proliferation and migration. Adenomatous polyposis coli (APC), a well-known negative regulator in Wnt signaling, has been proved to be a target of miRNA-192 and -215. Inhibition of miRNA-192 or -215 reduced the Topflash activities and repressed the expression of Wnt signaling pathway proteins, while APC small interfering RNAs reversed the inhibitory effects, suggesting that miRNA-192 and -215 activate Wnt signaling via APC. In addition, APC mediates the cell proliferation and migration regulated by miRNA-192 and -215. Furthermore, APC is downregulated in GC tissues and negatively correlated with the expression of miRNA-192 and -215. In summary, miRNA-192 and -215 target APC and function as oncogenic miRNAs by activating Wnt signaling in GC, revealing to be potential therapeutic targets.
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http://dx.doi.org/10.1002/jcp.29550DOI Listing
September 2020

Genipin increases oxaliplatin-induced cell death through autophagy in gastric cancer.

J Cancer 2020 1;11(2):460-467. Epub 2020 Jan 1.

Department of Oncology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea.

Oxaliplatin is used for treatment in combination with many drugs. However, the survival rate is still low due to side effects and drug resistance. Therefore, the combination with natural products was required for increasing efficacy and reducing side effects. Genipin, a natural product derived from the , associated with anti-angiogenic, anti-proliferative, hypertension, inflammatory, and the Hedgehog pathway. It is not known that genipin increases the therapeutic effect of oxaliplatin in gastric cancer. In this study, we found that genipin sensitizes oxaliplatin-induced apoptosis for the first time using colony forming assay, FACS analysis, and western blotting in gastric cancer. Additionally, genipin induced p53 expression in AGS, MKN45, and MKN28 cells. Also, genipin induced autophagy and LC3 expression. Knockdown of LC3 decreased cell death enhanced by the combination of oxaliplatin and genipin. In summary, we showed that genipin increases the oxaliplatin-induced cell death via p53-DRAM autophagy. Based on this, we suggest that genipin is a sensitizer of oxaliplatin.
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http://dx.doi.org/10.7150/jca.34773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930423PMC
January 2020

Elevated Risk for Sessile Serrated Polyps in African Americans with Endometrial Polyps.

Dig Dis Sci 2020 09 12;65(9):2686-2690. Epub 2019 Dec 12.

Pathology Department and Cancer Research Center, Howard University College of Medicine, Washington, DC, USA.

Background: Colorectal and endometrial lesions increase with age. It is not known if these two precursor lesions in sporadic cases associate with each other.

Aim: To determine the association between colorectal polyps and endometrial polyps (EP) in African Americans.

Methods: We reviewed records of patients referred to gynecology clinics and had colonoscopy at Howard University Hospital from January 2004 to December 2015. We defined cases as all patients who had EP and underwent colonoscopy. For controls, we used EP-free patients who underwent colonoscopy. Logistic regression analysis was used to assess the association between colon polyps and EP.

Results: The median age was 60 years in 118 Cases and 57 years in 664 Controls. The overall colorectal polyps prevalence in the two groups was not statistically different (54% in controls vs. 52% in cases, P = 0.60). Sessile serrated adenoma/polyps (SSPs) were more frequent in cases (8% vs. 2% in controls, P = 0.003). Sigmoid and rectal locations were more prevalent in controls than cases. In multivariate analysis and after adjusting for age, diabetes mellitus (DM), and BMI, SSPs were associated with EP occurrence with an odds ratio of 4.6 (CI 1.2-16.7, P = 0.022).

Conclusion: Colorectal polyp prevalence was similar in EP patients compared to EP-free controls. However, we observed a significant association between higher-risk SSPs in patients with EP. The prevalence of smoking and DM was higher in these patients. Females with EP might benefit from a screening for colonic lesions in an age-independent manner.
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http://dx.doi.org/10.1007/s10620-019-05991-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289663PMC
September 2020

Cannabidiol promotes apoptosis via regulation of XIAP/Smac in gastric cancer.

Cell Death Dis 2019 11 7;10(11):846. Epub 2019 Nov 7.

Department of Oncology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, 08308, Republic of Korea.

According to recent studies, Cannabidiol (CBD), one of the main components of Cannabis sativa, has anticancer effects in several cancers. However, the exact mechanism of CBD action is not currently understood. Here, CBD promoted cell death in gastric cancer. We suggest that CBD induced apoptosis by suppressing X-linked inhibitor apoptosis (XIAP), a member of the IAP protein family. CBD reduced XIAP protein levels while increasing ubiquitination of XIAP. The expression of Smac, a known inhibitor of XIAP, was found to be elevated during CBD treatment. Moreover, CBD treatment increased the interaction between XIAP and Smac by increasing Smac release from mitochondria to the cytosol. CBD has also been shown to affect mitochondrial dysfunction. Taken together, these results suggest that CBD may have potential as a new therapeutic target in gastric cancer.
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http://dx.doi.org/10.1038/s41419-019-2001-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838113PMC
November 2019