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"tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "62" "paginaFinal" => "67" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "N. Kamali, A. Talebi Bezmin Abadi, F. Rahimi, M. Forootan" "autores" => array:4 [ 0 => array:3 [ "nombre" => "N." "apellidos" => "Kamali" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:4 [ "nombre" => "A." "apellidos" => "Talebi Bezmin Abadi" "email" => array:1 [ 0 => "Amin.talebi@modares.ac.ir" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 2 => array:3 [ "nombre" => "F." "apellidos" => "Rahimi" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "M." "apellidos" => "Forootan" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Research School of Biology, The Australian National University, Canberra, Australia" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Identificación de <span class="elsevierStyleItalic">Helicobacter pylori</span> en biopsias tumorales obtenidas de pacientes con cáncer colorrectal: ¿indicación de una vacuna profiláctica?" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1075 "Ancho" => 2167 "Tamanyo" => 90219 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Gel electrophoresis showing the <span class="elsevierStyleItalic">glmM</span> PCR products. Lane 1: 100-bp DNA ladder, Lane 2: negative control, Lane 3: positive control, Lanes: 4, 6, 8, 9, 10, 11, 12 <span class="elsevierStyleItalic">glmM</span>-positive samples, and Lane 5 and 7: <span class="elsevierStyleItalic">glmM</span>-negative samples.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Helicobacter pylori</span> is a Gram-negative microorganism that colonizes the human gastric mucosa and causes occasional gastroduodenal diseases, driven by a Th1-mediated immune response, chronic leukocyte infiltration and chronic inflammation, and generation of reactive oxygen and reactive nitrogen species.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleItalic">H. pylori</span> is thought to be colonizing the human stomach mainly, but other sites also have been identified. Cumulative evidence shows that dental plaques may be a permanent <span class="elsevierStyleItalic">H. pylori</span> source in positive subjects. However, using different methods to detect <span class="elsevierStyleItalic">H. pylori</span> may potentially lead to diverse findings. The persistent production of reactive oxygen and reactive nitrogen species leads to cumulative production of <span class="elsevierStyleItalic">N</span>-nitroso compounds that cause DNA damage and mutations, leading to the development of gastric cancer in humans.<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">2–4</span></a> Additionally, bacterial interactions with the mammalian cells through the blood group antigen-binding adhesin (<span class="elsevierStyleItalic">babA</span>) leads to double-strand breaks in DNA.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">5</span></a> Subsequently, continual DNA damage, saturation of DNA-repair mechanisms, and imprecise DNA repair over time leads to carcinogenesis.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">5</span></a> Thus, this bacterium is the first and only one confirmed to cause gastric carcinogenesis.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Colorectal cancer (CRC) is the third cause of cancer-related deaths worldwide.<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">7,8</span></a> While host genetics and several environmental factors, including diet, are considered as major risk factors for CRC,<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">9</span></a> infectious risk factors of CRC have been explored and debated.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">10</span></a> Speculatively, carcinogenic effects due to <span class="elsevierStyleItalic">H. pylori</span> may not be limited to the stomach because recent reports have suggested some direct or indirect effects of <span class="elsevierStyleItalic">H. pylori</span> in the development of CRC.<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">11–13</span></a> For example, the roles of <span class="elsevierStyleItalic">H. pylori</span> in the formation of precancerous colorectal lesions and CRC development were investigated in case-control, metagenomic, and correlation/association studies, suggesting positive associations.<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">14–18</span></a> Therefore, colorectum is likely the second most affected organ by <span class="elsevierStyleItalic">H. pylori</span> infection.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">19</span></a> However, epidemiological studies so far cannot support a role for <span class="elsevierStyleItalic">H. pylori</span> as a risk factor for CRC development.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">20</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Because preventive strategies to reduce the global prevalence of CRC have generally been unsuccessful, learning more about the causal roles of <span class="elsevierStyleItalic">H. pylori</span> in the CRC development will lead to establishing novel, targeted therapeutic measures for CRC. We aimed to investigate the possible associations between <span class="elsevierStyleItalic">H. pylori</span> infection and CRC in the biopsy samples taken from Iranian CRC patients.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Participants, ethics, and sample collection</span><p id="par0020" class="elsevierStylePara elsevierViewall">Thirty-nine patients diagnosed with symptoms and histopathological features of CRC were enrolled. Ten subjects without CRC, as confirmed by colonoscopy findings and pathology reports, were included as control subjects; they did not have any polyps or colorectal inflammation. The exclusion criteria were incomplete colonoscopy, suboptimal bowel preparation, treatment with proton-pump inhibitors, treatment against <span class="elsevierStyleItalic">H. pylori</span> three months before colonoscopy, presence of non-adenomatous polyps, and pregnancy. Biopsy samples were collected from March 2017 to 1 August 2019. All CRC and control samples were collected at the Mehrad Hospital, Tehran, Iran, following standard surgical protocols performed by a practicing gastroenterologist. Two biopsy samples were taken from the tumor tissues by colonoscopy. Both samples were kept in a saline solution (0.9% w/v, pH 7). The first biopsy specimen was sent to the pathology department, while the second was transferred to the microbiology laboratory, Tarbiat Modares University, for further PCR analysis. All biopsy samples were examined by staining with hematoxylin and eosin (H&E) while Giemsa staining was used to confirm the positivity for <span class="elsevierStyleItalic">H. pylori</span>. All the experiments were performed in the department of pathology under supervision of an expert pathologist with<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>20 years’ experience. The study protocols were reviewed and approved by the ethics committee of Tarbiat Modares University, Tehran, Iran (Ethics code: IR.MODARES.REC.1397.240). All participating subjects signed the informed consent forms before undergoing colonoscopic surgery. Participation in the study was voluntary, and subjects were informed that they could disenroll whenever they wished. The participants filled in a questionnaire for demographic data (gender, history of surgery, alcohol consumption, and age).</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">DNA extraction and PCR</span><p id="par0025" class="elsevierStylePara elsevierViewall">Genomic DNA was extracted from the tumor biopsy samples by using a commercially available kit (ROJE Technologies/15105/Yazd, Iran) without modifications. Purified DNA was measured at 260<span class="elsevierStyleHsp" style=""></span>nm using a spectrophotometer (WPA, Biochrom, UK). Extracted DNA was kept at −20<span class="elsevierStyleHsp" style=""></span>°C before PCR experiments. Primer sequences for detection and confirmation of <span class="elsevierStyleItalic">glmM</span> included f-5′AAGCTTTTAGGGGTGTTAGGGGTTT and r-5′AAGCTTACTTTCTAACACTAACGC for confirming <span class="elsevierStyleItalic">H. pylori</span> infection. PCR conditions were 95<span class="elsevierStyleHsp" style=""></span>°C for 1<span class="elsevierStyleHsp" style=""></span>min; 58<span class="elsevierStyleHsp" style=""></span>°C, 1<span class="elsevierStyleHsp" style=""></span>min; and 72<span class="elsevierStyleHsp" style=""></span>°C, 1<span class="elsevierStyleHsp" style=""></span>min, for 37 cycles. <span class="elsevierStyleItalic">glmM</span> PCR was performed in a 20-μL mixture containing at least 100<span class="elsevierStyleHsp" style=""></span>ng DNA, 150<span class="elsevierStyleHsp" style=""></span>μM of each dNTPs (Gibco BRL, USA), 1× PCR buffer (20<span class="elsevierStyleHsp" style=""></span>mM Tris–HCl, pH 8.5), 50<span class="elsevierStyleHsp" style=""></span>mM KCl, 2<span class="elsevierStyleHsp" style=""></span>mM MgCl<span class="elsevierStyleInf">2</span>, 0.75<span class="elsevierStyleHsp" style=""></span>μM of each primer, and 2 units of Taq polymerase (Gibco BRL, USA). PCR was performed in a T100 Thermal Cycler (Bio-Rad, Berkeley, California). A previously confirmed sample was used as the positive control, and distilled water was used instead of the DNA template to serve as the negative control.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Gel electrophoresis</span><p id="par0030" class="elsevierStylePara elsevierViewall">PCR products were electrophoresed in 1% agarose (CinnaGen, Tehran, Iran) gels in 1× TAE buffer (40<span class="elsevierStyleHsp" style=""></span>mM Tris, 20<span class="elsevierStyleHsp" style=""></span>mM acetic acid, and 1<span class="elsevierStyleHsp" style=""></span>mM EDTA, pH 8.0) and visualized under an ultraviolet transilluminator (Biometra, Germany). The PCR product was at approximately 294<span class="elsevierStyleHsp" style=""></span>bp after electrophoresis.<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">21</span></a> Two independent operators determined the positivity of the PCR reactions.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Statistical analyses</span><p id="par0035" class="elsevierStylePara elsevierViewall">We used the SPSS version 18 for statistical analyses. The distribution of positive samples in each group and the colonization with <span class="elsevierStyleItalic">H. pylori</span> was investigated using a two-tailed Fisher's exact test. The significance level was considered as 0.05.</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Results</span><p id="par0040" class="elsevierStylePara elsevierViewall">From 49 patients included in our study, 39 were diagnosed with CRC; 10 had no record of CRC and were included as the control group. The mean age of the participants was 54, ranging from 38 to 79 years. In the CRC group, 18 (46.1%) were female, whereas six (60%) were female in the control group. No significant association was observed between family history of cancer, age, and gender. Of the 49 biopsies, 20 (40%) samples were positive for <span class="elsevierStyleItalic">H. pylori</span> by <span class="elsevierStyleItalic">glmM</span>-specific PCR (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Among the CRC biopsy samples, 20 of 39 (51%) were positive; however, we found none of the control biopsies to be positive for <span class="elsevierStyleItalic">H. pylori</span> (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.003). The categorization of the CRC cases based on pathology reports and based on the level of active inflammation is shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Thirty-one (79%) of the CRC samples presented with severe inflammation. Out of the 31 CRC patients with severe inflammation, 18 (58%) were positive for <span class="elsevierStyleItalic">H. pylori</span> (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05). One positive case each was categorized as presenting mild or moderate inflammation.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Discussion</span><p id="par0045" class="elsevierStylePara elsevierViewall">Although a positive association between gastric cancer and <span class="elsevierStyleItalic">H. pylori</span> infection has been confirmed, the clinical and mechanistic correlations between CRC and <span class="elsevierStyleItalic">H. pylori</span> infection are still unknown. We found a relatively high incidence of <span class="elsevierStyleItalic">H. pylori</span> infection, 20 out of 39 (51%) cases, in the tumor tissues of the CRC patients. Such an incidence of <span class="elsevierStyleItalic">H. pylori</span> in association with CRC had not been reported previously, thus highlighting the importance of strengthening the relevant gastroenterological research efforts.</p><p id="par0050" class="elsevierStylePara elsevierViewall">We used a highly specific and sensitive method for detection of <span class="elsevierStyleItalic">H. pylori</span> based on <span class="elsevierStyleItalic">glmM</span> PCR. Previously, mainly serological tests were used to determine the association between <span class="elsevierStyleItalic">H. pylori</span> infection and the CRC cases.<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">22–25</span></a> Grahn et al. used the 16s rDNA PCR, reporting that 27% of tumor tissues were infected with <span class="elsevierStyleItalic">H.</span><span class="elsevierStyleItalic">pylori</span><a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">26</span></a> (almost half of the 51% rate we report here). Additionally, Monstein et al. reported that five out of 19 (26%) biopsy specimens were infected with <span class="elsevierStyleItalic">H. pylori</span>, but they investigated microscopic colitis not CRC.<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">27</span></a> Butt et al. studied a large consortium of cohorts and used serological testing for VacA of <span class="elsevierStyleItalic">H. pylori</span>, reporting an increased risk of developing CRC.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">17</span></a> However, they did not confirm the presence of <span class="elsevierStyleItalic">H. pylori</span> in the tumor tissues. In contrast, we found the presence of <span class="elsevierStyleItalic">H. pylori</span> in almost half of the tumor samples obtained from CRC patients.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Altogether our results and the previous literature suggest that identifying <span class="elsevierStyleItalic">H. pylori</span> in tumor tissues derived from CRC may not represent a causal relationship. So far, identification of <span class="elsevierStyleItalic">H. pylori</span> in other tumor tissues had not been translated into a direct causal relationship, but the high probability of such a causal association should not be discounted. Deciphering and confirming such an etiological association are relevant in countries like Iran where CRC is highly prevalent and leads to high mortality rates. Likewise, reconsidering the current therapeutic strategies and updating them are important. We speculate that treatment against <span class="elsevierStyleItalic">H. pylori</span> may hold promise in the management of CRC patients; this will need to be confirmed by clinical trials. The global fight for reducing the CRC prevalence will require international attempts to control and remove all the relevant risk factors, including <span class="elsevierStyleItalic">H. pylori</span> infection, in patients and their first-line relatives.</p><p id="par0060" class="elsevierStylePara elsevierViewall">To present a clearer conclusion, we could have collected antral biopsies from both control subjects and patients for comparison; however, our ethics conditions were limited to taking specimens by colonoscopic surgery. Confirming the presence of <span class="elsevierStyleItalic">H. pylori</span> in colon tumors and in the antral biopsy samples would constitute valuable data in this high-risk population.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Although the majority of the CRC patients are older than 60, at least, in the developing countries such as Iran,<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">8,25</span></a> we did not find a significant association between the risk of CRC and old age among the study subjects between 50 to 60 years of age; this observation may be due to the limited sample size used in our study. Unfortunately, recent global trends indicate an increasing prevalence of CRC among younger patients.<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">28</span></a> Thus, to screen the high-risk populations for <span class="elsevierStyleItalic">H. pylori</span> infection may be important also in the management of CRC. Screening by using colonoscopic surgery may be unfeasible routinely, but alternative practical diagnostic tests, for example, urea breath testing or determining seropositivity in fecal samples, could be developed to facilitate the subsequent, appropriate treatment measures against <span class="elsevierStyleItalic">H. pylori</span> during the management of CRC.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Presently, four critical pathological explanations may be offered to rationalize the association between <span class="elsevierStyleItalic">H. pylori</span> and CRC:</p><p id="par0075" class="elsevierStylePara elsevierViewall">First, some of the cell-wall components of <span class="elsevierStyleItalic">H. pylori</span> may act as carcinogens following interactions with mammalian cells.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">5</span></a> The turnover of <span class="elsevierStyleItalic">H. pylori</span> in the human gastroduodenal tract has made this rationale logical because the epithelial cells are exposed to many of the secreted proteins or polysaccharides derived from the surface of <span class="elsevierStyleItalic">H. pylori</span>.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Second, the initial T-cell infiltration following the primary inflammation in the gastric mucosal cells is relatively high, whereas this infiltration wanes after successful eradication of this bacterium.<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">29</span></a> Additionally, chronic inflammation following the gastric colonization by <span class="elsevierStyleItalic">H. pylori</span> increases the chance of cyclooxygenase-2 production, resulting in a severe prognosis for colorectal polyps.<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">30,31</span></a> Adenomatous colorectal polyps tend to develop into CRC foci.<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">32</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Third, hypergastrinemia, caused by <span class="elsevierStyleItalic">H. pylori</span> in the gastric mucosa by increased production of gastrin, is a major predisposing factor for gastrointestinal carcinogenesis.<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">33,34</span></a> Broadly defined, <span class="elsevierStyleItalic">H. pylori</span> infection is closely associated with exaggerated gastrin release in the human stomach, and thereafter, in the colons.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Fourth, infection with the virulent <span class="elsevierStyleItalic">H. pylori</span> strains may be predisposing to, or preceding, the development of CRC. For instance, infection with CagA-positive <span class="elsevierStyleItalic">H. pylori</span> was shown to increase the risk of CRC.<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">35</span></a> However, we included the patients without gastric cancer in our study; whereas, all subjects in the study by Shumuely et al. were confirmed to have gastric cancer.<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">35</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Antibiotic therapy has been suggested to help in the management of <span class="elsevierStyleItalic">H. pylori</span> infections while <span class="elsevierStyleItalic">H. pylori</span> eradication also has been the healthcare focus in the previous decade. However, no prophylactic vaccine against the <span class="elsevierStyleItalic">H</span>. <span class="elsevierStyleItalic">pylori</span> infection has been validated. The CRC patients are usually diagnosed at their 50<span class="elsevierStyleHsp" style=""></span>s; thus, such early diagnosis allows for sufficient time to eliminate the infection and lower the chance of CRC progression to severe stages. Our findings highlight the importance of the prophylactic measures and pave the way to future research in this arena.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conclusion</span><p id="par0100" class="elsevierStylePara elsevierViewall">Preventive and therapeutic strategies to manage the CRC patients may need to be revised. A promising approach would be to consider a prophylactic vaccine for subjects who are the first-line relatives of the CRC patients and are positive for <span class="elsevierStyleItalic">H. pylori</span>. Screening for <span class="elsevierStyleItalic">H. pylori</span> infections in the CRC patients and their relatives should be considered as an early strategy for CRC detection and management.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Authors’ contributions</span><p id="par0105" class="elsevierStylePara elsevierViewall">Conceptualization: Amin Talebi Bezmin Abadi; Methodology: Amin Talebi Bezmin Abadi, Negin Kamali; Formal analysis and investigation: Amin Talebi Bezmin Abadi, Negin Kamali, Mojgan Forootan, Farid Rahimi; Writing – initial drafting: Amin Talebi Bezmin Abadi, Negin Kamali; Writing – review and editing: Amin Talebi Bezmin Abadi, Negin Kamali, Farid Rahimi, Mojgan Forootan; Funding acquisition: Amin Talebi Bezmin Abadi; Resources: Amin Talebi Bezmin Abadi; Supervision: Amin Talebi Bezmin Abadi. All authors equally contributed to finalizing the paper and approved it for submission.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Ethical approval</span><p id="par0110" class="elsevierStylePara elsevierViewall">All procedures were done according to the ethical standards of the institutional and/or national research committee and abiding by the 1964 Declaration of Helsinki and its later amendments. The study was approved by the institutional Ethics Committee (IR.MODARES.REC.1397.240).</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Informed consent</span><p id="par0115" class="elsevierStylePara elsevierViewall">Participants signed the informed consent forms.</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Funding</span><p id="par0120" class="elsevierStylePara elsevierViewall">The authors acknowledge the research deputy of Tarbiat Modares University, Iran, for financially supporting this project.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflict of interest</span><p id="par0125" class="elsevierStylePara elsevierViewall">The authors have no potential conflict of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:15 [ 0 => array:3 [ "identificador" => "xres1525297" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1382874" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1525296" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1382873" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Participants, ethics, and sample collection" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "DNA extraction and PCR" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Gel electrophoresis" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical analyses" ] ] ] 6 => array:2 [ "identificador" => "sec0035" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0045" "titulo" => "Conclusion" ] 9 => array:2 [ "identificador" => "sec0050" "titulo" => "Authors’ contributions" ] 10 => array:2 [ "identificador" => "sec0055" "titulo" => "Ethical approval" ] 11 => array:2 [ "identificador" => "sec0060" "titulo" => "Informed consent" ] 12 => array:2 [ "identificador" => "sec0065" "titulo" => "Funding" ] 13 => array:2 [ "identificador" => "sec0070" "titulo" => "Conflict of interest" ] 14 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-07-31" "fechaAceptado" => "2020-09-28" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1382874" "palabras" => array:7 [ 0 => "Colorectal cancer" 1 => "<span class="elsevierStyleItalic">Helicobacter pylori</span>" 2 => "PCR" 3 => "Prevention" 4 => "Screening program" 5 => "Tumor" 6 => "Vaccine" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1382873" "palabras" => array:7 [ 0 => "Cáncer colorrectal" 1 => "<span class="elsevierStyleItalic">Helicobacter pylori</span>" 2 => "PCR" 3 => "Prevención" 4 => "Programa de cribado" 5 => "Tumor" 6 => "Vacuna" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The association between <span class="elsevierStyleItalic">H. pylori</span> infection and colorectal cancer (CRC) has been controversial, and despite the undisputed roles of <span class="elsevierStyleItalic">H. pylori</span> in the etiology of gastric cancer, its involvement as a causative agent of CRC is unknown. We aimed to investigate the potential associations between <span class="elsevierStyleItalic">H. pylori</span> infection and CRC in biopsy samples taken from tumors of Iranian patients. Patients (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>49; aged 38–79 years, mean age<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>49) with diagnosed CRC were enrolled. Biopsies from control (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>10) and suspected CRC patients were collected from March 2017 to 1 August 2019 at the Mehrad Hospital, Tehran, Iran. The diagnosis of CRC was confirmed by pathology and colonoscopic examinations. An expert gastroenterologist performed the colonoscopic surgery and sample collection. DNA was extracted from the samples, and <span class="elsevierStyleItalic">H. pylori</span> infection was detected and confirmed by PCR using the <span class="elsevierStyleItalic">glmM</span> sequence as the species-specific gene. SPSS version 18 was used to determine the significant associations by using the two-tailed Fisher's exact test. Eighteen (46.1%) and 6 (60%) patients were female in the CRC and control groups, respectively. No significant associations were observed between <span class="elsevierStyleItalic">H. pylori</span> infection and family history of cancer, age, or gender. Thirty-one (79%) CRC samples showed severe inflammation. Out of the 31 CRC samples with severe inflammation, 18 (58%) were positive for <span class="elsevierStyleItalic">H. pylori</span> (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05). We conclude that <span class="elsevierStyleItalic">H. pylori</span> may be involved in the CRC pathogenesis or progression. Our findings suggest that a prophylactic vaccine against <span class="elsevierStyleItalic">H. pylori</span> may be promising in reducing the CRC incidence.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">La asociación entre la infección por <span class="elsevierStyleItalic">H. pylori</span> y el cáncer colorrectal (CCR) ha sido controversial y, a pesar del papel indiscutible de <span class="elsevierStyleItalic">H. pylori</span> en la etiología del cáncer gástrico, se desconoce su participación como agente causante del CCR. Nuestro objetivo consistió en investigar las posibles asociaciones entre la infección por <span class="elsevierStyleItalic">H. pylori</span> y el CCR en muestras de biopsia tomadas de tumores de pacientes iraníes. Pacientes (n = 49) de 38 a 79 años de edad (edad media = 49) con diagnóstico de CCR fueron admitidos. Las biopsias de los pacientes de control (n = 10) y sospechosos de CCR se recolectaron desde marzo de 2017 hasta el 1 de agosto de 2019 en el Hospital Mehrad, Teherán, Irán. El diagnóstico de CCR se confirmó mediante exámenes anatomopatológicos y colonoscópicos. Un gastroenterólogo experto realizó la cirugía colonoscópica y la toma de muestras. Se extrajo ADN de las muestras y se detectó y confirmó la infección por <span class="elsevierStyleItalic">H. pylori</span> mediante PCR utilizando la secuencia glmM como gen específico de la especie. Se utilizó la versión 18 de SPSS para determinar las asociaciones significativas mediante la prueba exacta de Fisher de dos colas. Dieciocho (46,1%) y 6 (60%) pacientes en el grupo de CCR y de control, respectivamente, fueron mujeres. No se observaron asociaciones significativas entre la infección por <span class="elsevierStyleItalic">H. pylori</span> y los antecedentes familiares de cáncer, la edad o el sexo. Treinta y una (79%) muestras de CRC mostraron inflamación severa. De las 31 muestras de CCR con inflamación severa, 18 (58%) fueron positivas para <span class="elsevierStyleItalic">H. pylori</span> (P < 0,05). Concluimos que H. pylori puede estar involucrado en la patogénesis o progresión del CCR. Nuestros hallazgos sugieren que una vacuna profiláctica contra <span class="elsevierStyleItalic">H. pylori</span> puede ser prometedora para reducir la incidencia de CCR.</p></span>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1075 "Ancho" => 2167 "Tamanyo" => 90219 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Gel electrophoresis showing the <span class="elsevierStyleItalic">glmM</span> PCR products. Lane 1: 100-bp DNA ladder, Lane 2: negative control, Lane 3: positive control, Lanes: 4, 6, 8, 9, 10, 11, 12 <span class="elsevierStyleItalic">glmM</span>-positive samples, and Lane 5 and 7: <span class="elsevierStyleItalic">glmM</span>-negative samples.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Pathology report (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>39) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span>-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Severe</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>31 (79%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Moderate</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>5 (12.8%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Mild</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>3 (7.6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2621554.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Distribution of levels of active inflammation in the 39 biopsy samples.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:35 [ 0 => array:3 [ "identificador" => "bib0180" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "<span class="elsevierStyleItalic">Helicobacter pylori</span>: molecular basis for colonization and survival in gastric environment and resistance to antibiotics. 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Original article
Identification of Helicobacter pylori in tumor biopsies obtained from patients with colorectal cancer: Indication for a prophylactic vaccine?
Identificación de Helicobacter pylori en biopsias tumorales obtenidas de pacientes con cáncer colorrectal: ¿indicación de una vacuna profiláctica?
a Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
b Research School of Biology, The Australian National University, Canberra, Australia
c Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran