afshin abdirad

Variations in mitochondrial DNA copy number (mtDNA-CN) of peripheral blood leukocytes (PBLs), as a potential biomarker for gastric cancer (GC) screening has currently been subject to controversy. Herein, we have assessed its efficiency in GC screening, in parallel and in combination with serum pepsinogen (sPG) I/II ratio, as an established indicator of gastric atrophy.

The study population included GC (n = 53) and non-GC (n = 207) dyspeptic patients. The non-GC group was histologically categorized into CG (n = 104) and NM (n = 103) subgroups. The MtDNA-CN of PBLs was measured by quantitative real-time PCR. The sPG I and II levels and anti-H. pylori serum IgG were measured by ELISA.

The mtDNA-CN was found significantly higher in GC vs. non-GC (OR = 3.0; 95% CI = 1.4, 6.4) subjects. Conversely, GC patients had significantly lower sPG I/II ratio than the non-GC (OR = 3.2; CI = 1.4, 7.2) subjects. The combination of these two biomarkers yielded a dramatic amplification of the odds of GC risk in double-positive (high mtDNA-CN-low sPGI/II) subjects, in reference to double-negatives (low mtDNA-CN-high sPGI/II), when assessed against non-GC (OR = 27.1; CI = 5.0, 147.3), CG (OR = 13.1; CI = 2.4, 72.6), or NM (OR = 49.5; CI = 7.9, 311.6) groups.

The combination of these two biomarkers, namely mtDNA-CN in PBLs and serum PG I/II ratio, drastically enhanced the efficiency of GC risk assessment, which calls for further validations.

Two of the Wnt signaling pathway target genes, tumor necrosis factor receptor family member (TROY) and leucine-rich G-protein coupled receptor (LGR5), are involved in the generation and maintenance of gastrointestinal epithelium. A negative modulatory role has recently been assigned to TROY, in this pathway. Here, we have examined their simultaneous expression in gastric carcinogenesis. Tumor and paired adjacent tissues of intestinal-type gastric cancer (GC) patients (n = 30) were evaluated for LGR5 and TROY expression by immunohistochemistry. The combination of the percentage of positively stained cells and the intensity of staining was defined as the composite score and compared between groups. The obtained findings were re-evaluated in a mouse model. TROY expression in the tumor tissue was significantly lower than that of the adjacent tissue (2.5 ± 0.9 vs. 3.3 ± 0.9, p = 0.004), which was coincident with higher LGR5 expression (3.6 ± 1.1 vs. 2.7 ± 0.9, p = 0.001). This observation was prominent at stages II/III of GC, leading to a statistically significant mean difference of expression between these two molecules (p = 0.005). In the H. pylori infected-mouse model, this inverse expression was observed in transition from early (8-16 w) to late (26-50 w) time points, post treatment (p = 0.002). Our data demonstrates an inverse trend between TROY down-regulation and LGR5 up-regulation in GC tumors, as well as in response to H. pylori infection in mice. These findings support a potential negative modulatory role for TROY on LGR5 expression.

  Different studies have investigated the overexpression of human epidermal growth factor receptor 2 in ovarian cancers, in addition to the association between the level of its overexpression and tumor characteristics (tumor grade, subtype, stage, and prognosis). However, the prognostic significance of human epidermal growth factor receptor 2/neu dysregulation in epithelial ovarian tumors is controversial. The current study aims to assess human epidermal growth factor receptor 2 overexpression in different types and stages of epithelial borderline and malignant ovarian tumors in a population of Iranian patients. We conducted this cross-sectional study on 100 patients diagnosed with epithelial borderline and malignant ovarian tumors who referred to the Cancer Institute of Imam Khomeini Hospital at Tehran between 2012 and 2014. After selection of the appropriate tissue block, we prepared slides for immunohistochemical staining with the human epidermal growth factor receptor 2 marker. Human epidermal growth factor receptor 2 positivity was evaluated and scored according to Ellis and Wolff recommendations. Cases with equivocal immunohistochemical results (score 2) also underwent chromogenic in situ hybridization. The most prevalent tumor in our study was serous carcinoma (54%). Human epidermal growth factor receptor 2 scores were: 0 in 69%, 1+ in 26%, 2+ in 4%, and 3+ in 1% of tumors. Chromogenic in situ hybridization examination of cases with human epidermal growth factor receptor 2 score of 2 showed negative results for human epidermal growth factor receptor 2 gene amplification. We observed no association between human epidermal growth factor receptor 2 and the level of tumor differentiation, histologic subtype, clinical stage, tumor size, and patient’s age. Controversial results and wide range of prevalence in human epidermal growth factor receptor 2 overexpression in different studies could be due to several causes. Technical considerations, tumor heterogeneity, and lack of standard guidelines for interpretation could influence the results. We did not find any relationship between human epidermal growth factor receptor 2 overexpression and prognostic indices of grade, clinical stage or histologic subtype as many other reports. Future studies should be conducted on larger numbers of patients with different disease stages and adequate numbers of different histologic subtypes

We studied the number of lymph nodes (LN) assessed in gastric cancer, and evaluated the association between different factors and a lower number of LN assessed.
We conducted a retrospective study in three hospitals in Tehran city, I.R. Of Iran. We used patient medical and pathological reports and obtained personal and clinical information. We studied the association of being on the N3 stage with the number of assessed lymph nodes (NALN), gender, tumor size, T stage, hospital, tumor site, histopathological diagnosis, tumor grade and age at diagnosis. In addition, we estimated the association between NALN and different clinical variables. A logistic regression model estimated the crude and adjusted odds ratios (OR) and corresponding 95% confidence intervals (95% CI).
The average number of NALN was 10.48 (±6.9). We found that the probability of being diagnosed as stage N3 was significantly lower in patients who had less than 15 LN assessed compared to those who had more than 15 LN assessed in their pathology reports (OR=0.2; 95% CI 0.1-0.4). The hospital, tumor sizes were significantly associated with NALN.
Lower NALN led to stage migration and underestimation of the real tumor stage in GC patients. The LN assessments were lower than recommended by the American Joint Cancer Clinician Association in all the three hospitals included in this study. Developing national guidelines, training surgeons and pathologists, conducting regular monitoring and evaluation of the data is necessary to increase NALN and thus improve the staging of GC patients.

Gastric cancer arises, mainly, on an inflammatory background. Helicobacter pylori neutrophil activating (HP-NAP) protein functions as a potent pro-inflammatory mediator. Similarly, IL-4 plays a critical role in the inflammation pathway, the levels of which are altered by C to T transition at position -590 in its promoter region. Here, we have aimed to assess the risk of gastritis and gastric cancer in the co-presence of these two inflammation modulating mediators.
Gastritis (n=58) and gastric cancer (n=31) patients were evaluated and compared with H. pylori-positive asymptomatic controls (n=46), for serum antibodies against recombinant HP-NAP and IL-4 C-590T single nucleotide polymorphism using immunoblotting and PCR-RFLP, respectively. Multivariable logistic regression, adjusting for age, gender and ethnicity, was used for data analysis.
In terms of susceptibility to gastritis, seropositivity to HP-NAP projected a risk impact of 4.62 fold (OR=4.62, 95% CI=1.50-14.22), which when present in IL-4 -590 T carriers augmented the risk up to 9.7 fold (OR=9.70, 95% CI=2.06-45.69). A similar pattern, but of a stronger magnitude, occurred for the risk of gastric cancer, which was estimated at 9.07 fold (OR=9.07, 95% CI=1.99-42.0) for HP-NAP-seropositive subjects and was drastically amplified (OR=33.64, 95% CI=2.06-548.68), when double-positive (HP-NAP seropositive/IL-4 -590 T carrier) subjects were examined against double negatives (HP-NAP seronegative/IL-4 -590 CC).
Our preliminary data indicate that serum antibodies against HP-NAP represent a state of risk, which is further exacerbated in IL-4 -590 T carriers. These biomarkers, if validated in larger prospective studies, can be used to screen for gastric cancer susceptibility.

Studies have shown that obese individuals are at increased risk of breast cancer development and poorer prognosis. Leptin, an adipose tissue-derived hormone, has pro-inflammatory and proliferative effects and a well-established association with several comorbidities of obesity. This study was designed and conducted to compare the serum levels of leptin in patients with malignant and benign breast lesions. A cross-sectional study was conducted in Research Center of Cancer Institute, Tehran, Iran between 2010 and 2011. Sixty-five patients with breast cancer and 65 BMI-matched patients with benign breast lesions were enrolled in this study. The serum leptin level was measured by the ELISA method and compared between the two groups. A total of 130 patients were collected. The mean BMI in benign and malignant groups was 25.2±3.2 and 25.8±3.8 (kg/m2), respectively. Circulating levels of leptin were 20.05±14.69 vs. 14.74±10.16 mL in malignant and benign groups, respectively (P=0.011). A positive correlation was observed between BMI and leptin concentration (r = 0.431, P < 0.001). Leptins levels were not associated with the patients’ age (P = 0.108), menstrual status (P = 0.214), and history of OCP use (P = 0.269). Our findings suggest that patients with breast cancer have significantly higher levels of leptin compared to those with benign lesions.

Serologic screening of gastric cancer (GC) by serum pepsinogens (sPG) levels and Helicobacter pylori (Hp) sero-status, though highly informative, has provided heterogeneous results. Here, we have evaluated the modifying effects of demographic factors on the risk impact of Hp sero-status/sPG levels in gastric cancer, with particular emphasis on age. A cross-sectional study was carried out on 1341 individuals (GC = 578, healthy = 763), who were stratified into two age groups: 35-59 years (middle-aged, n = 830) and ≥ 60 years (60 years-plus, n = 511). Demographic factors and serological states (Hp sero-staus and sPG levels) were recorded by subject interview and serum ELISAs, respectively. Covariate-specific odds ratios were calculated by multivariable logistic regression. Hp infection was consistently associated with increased sPGI and sPGII levels in the 60 year-plus, but not the middle-aged group. The joint examination of the variable states of the three serum biomarkers (Hp serology, sPGI, and sPGI/II ratio), in the 60 year-plus age group, demonstrated a stepwise escalation of risk from the single (sPGIlow; OR = 2.6), to double (sPGIlow/sPGI/IIlow; OR = 3.55, and Hppositive/sPGIlow; OR=5.0) and ultimately triple (Hppositive/PGIlow/PGI/IIlow; OR=10.48) positive states, in reference to the triple negatives. However, this pattern was not exhibited in the middle-aged subjects. Age was clearly identified as a modifying factor on the risk projection of the combined states of Hp serology and sPG levels in gastric cancer screening, reflected by the augmented (~10.5 fold) risk of GC in the triple positive (Hppositive/sPGIlow/sPGI/IIlow) 60 year-plus subjects, which was not evident in the middle-aged group.

Considering molecular target therapy concept in the treatment of oral squamous cell carcinoma (OSCC), many attempts have been performed to introduce an effective molecular marker during recent years. Several investigations have emphasized on the role of CD44 in variouscancers and few studies have mentioned CD24 and CD74. The purpose of this study was to investigate the relationship between CD44, CD24 and CD74 expressions and several clinical or histopathological factors in OSCC patients. In our analytical cross-sectional study, forty primary OSCC specimens were immunohistochemically stained for CD44, CD24, and CD74 proteins. Then, the relationship between their expressions and age, sex, lymph node metastasis, and histopathologic grading was statistically analyzed using Mann-Whitney nonparametric and t-test. Furthermore, P < 0. was considered as signifi cant. CD44 and CD74 proteins were signifi cantly over-expressed in OSCC patients with high grade (P = 0.001 and P = 0.001) as compared to those with low grade. Furthermore, CD74 immunoreactivity showed signifi cantly higher expression in patients with lower age (P = 0.039). Considering lymph node metastasis, we observed signifi cant overexpression of CD74 in patients with no lymph node involvement (P = 0.033). Our observations support the signifi cant role of membranous CD44 protein in progression of OSCC and also introduce CD74 protein as a probable interfering factor in different aspects of OSCC.

Primary malignant esophageal melanoma makes up 0.1% to 0.2% of all esophageal malignancies. Most physicians assume malignant melanoma as a skin originated neoplasm, however this type of melanoma can occur anywhere in the gastrointestinal tract especially in the esophagus. Thus, it is essential to consider malignant melanoma in differential diagnosis of any esophagus masses.. In this study introduces a case of primary malignant esophageal melanoma and the method of investigation based on the patient’s complains. Then, evaluates the best method of treatment and assess prognosis and survival of our studied case. Macroscopic pathology findings include 5 × 3.5 cm tumor which was located in the one-third distal part of the esophagus. Moreover, pathology investigations reported melanoma tumor cells with melanin granules in squamous epithelium of esophagus with submucosal invasion.. In order to detect malignant melanoma as soon as possible, whole body examinations are required. Besides, the patient’s complaints are important as well. After malignancy exploration, selection of the most appropriate treatment is the ultimate goal. Education of health care providers reduces the burden of such malignancy for both patients and the health care system..

Menetrier''s disease or hypertrophic gastritis is a premalignant rare disease that often presents with hypertrophy in the gastric folds, hypoalbuminemia and decreased acid secretion. There are a few papers worldwide that report concomitant Menetrier''s disease and ulcerative colitis (U.C), however none are from Iran. This is the first case reported in Iranian literature. The pathogenesis of this coexistence is unknown. We report the case of a 28-year-old woman with intermittent bilateral edema of the lower extremities, weight loss and epigastric pain associated with chronic intermittent diarrhea and one episode of nocturnal dysentery. Paraclinical evaluations showed hypoalbuminemia, low serum protein level, severe 25 OH vitamin D deficiency, a positive Helicobacter pylori urea breath test and negative cytomegalovirus (CMV) IgM antibody. Histologic, radiologic and endoscopic findings were consistent with Menetrier''s disease associated with U.C. The patient was prescribed mesalazine, asacol suppositories and pantoprazole.During a follow up visit the patient noted improvement in her symptoms. She was referred to a surgeon to discuss additional possible therapeutic treatments.

Viruses, such as human Papillomavirus (HPV), have been detected in benign breast tissues and breast tumors and are considered to be involved in the etiology of breast cancer, but there are controversial data on the meaning of viral induction of breast cancer. The aim of this study was to investigate the presence of human Papillomavirus (HPV) in Iranian patients with breast carcinoma. In this case- control study, paraffin-embedded sections from 64 female patients with breast carcinoma and 53 breast tissues from patients with fibrocystic disease, as control, were analyzed for presence of HPV DNA. Real-Time PCR was used to amplify consensus GP5+/GP6+ HPV sequences. HPV DNA sequences were detected in 3 of the 53 benign breast tissue samples, but none of the breast carcinoma samples was identified. Our analysis could not confirm a role of HPV in breast cancer.

Gastrointestinal (GI) cancers are a significant source of morbidity and mortality in Iran, with stomach adenocarcinoma as the most common cancer in men and the second common cancer in women. Also, some parts of Northern Iran have one of the highest incidences of esophageal cancer in the world. Multi-disciplinary organ-based joint clinics and tumor boards are a well-recognized necessity for modern treatment of cancer and are routinely utilized in developed countries, especially in major academic centres. But this concept is relatively new in developing countries, where cancer treatment centres are burdened by huge loads of patients and have to cope with a suboptimum availability of resources and facilities. Cancer Institute of Tehran University of Medical Sciences is the oldest and the only comprehensive cancer treatment centre in Iran, with a long tradition of a general tumor board for all cancers. But with the requirements of modern oncology, there has been a very welcome attention to sub-specialized organ-based tumor boards and joint clinics here in the past few years. Considering this, we started a multi-disciplinary tumor board for GI cancers in our institute in early 2010 as the first such endeavor here. We hereby review this 2-year evolving experience. The process of establishment of a GI tumor board, participations from different oncology disciplines and related specialties, the cancers presented and discussed in the 2 years of this tumor board, the general intents of treatment for the decisions made and the development of interest in this tumor board among the Tehran oncology community will be reviewed. The GI tumor board of Tehran Cancer Institute started its work in January 2010, with routine weekly sessions. A core group of 2 physicians from each surgical, radiation and medical oncology departments plus one gastroenterologist, GI pathologist and radiologist was formed, but participation from all interested physicians was encouraged. An electronic database was kept from the beginning. The number of patients presented in the tumor board increased from 4 in January 2010 to 16 in December 2011. Most patients were presented by radiation oncology department (38%) and then surgical (36%) and medical oncology (20%) departments. Physicians’ participation also grew from an average of 8 each session to 12 in the same months, with a number of cancer specialists taking part from other university hospitals in Tehran. A total number of 225 patients were presented with a treatment decision made in this 2-year period. The majority of cases were colorectal (32%), stomach (23%), and esophageal (17%) cancers. The number of pancreatic (7%) and hepatobiliary (6%) cancers were much smaller. Most decisions were for a primary treatment (surgery or radiochemotherapy) and then a neoadjuvant approach. Tehran Cancer Institute's GI tumor board is one of the first multi-disciplinary organ-based tumor boards in Iran, and as such has made a successful start, establishing itself as a recognized body for clinical decisions and consultations in GI oncology. This experience is growing and evolving, with newer presentation and discussion formats and adapted guidelines for treatment of GI cancers in Iran sought.

Attempts for early detection of gastric cancer have recently focused on host''s genetic susceptibility factors and gene-environment interactions. We have، herein، studied the association of MTHFR C677T single nucleotide polymorphism (SNP) and its interaction with Helicobacter pylori infection، smoking، age and gender on the risk of gastric cancer among an Iranian population. Gastric cancer patients (n = 450) and cancer-free controls (n = 780) were studied for serum H. pylori-specific IgG antibodies by ELISA and MTHFR C677T polymorphism (SNP) by PCR-RFLP. Demographic and life style data were collected through patient interviews. Unconditional logistic regression model estimated odds ratio (OR) and the corresponding 95% confidence intervals (CI). The interactions of MTHFR genotype with H. pylori infection (P = 0. 03)، age (P = 0. 049) and gender (P = 0. 007) were statistically significant. Accordingly، MTHFR C677T carriers who were also positive for H. pylori infection exhibited 80% (OR = 1. 8، 95% CI = 1. 0-2. 9) significant excess risk of non-cardia gastric cancer. Furthermore، subjects over the age of 50 or female subjects carrying MTHFR C677T SNP showed 40 (OR = 1. 4، 95% CI = 1. 0-2. 0) and 100 (OR = 2. 0، 95% CI = 1. 2-3. 2) percent increased risk of gastric cancer، respectively. Therefore، MTHFR C677T SNP seems to increase the risk of gastric cancer and the effect is significantly inflated by interactions with H. pylori infection، age and gender.

Aim and Endometriosis is a common gynecological disorder that is poorly understood. It is characterized by the presence of uterine endometrial tissue outside the uterine cavity and is mainly associated with severe pelvic pain and/or infertility. We hypothesized that viral infection endometrium (especially HPV) may increase the capacity for the invasiveness of basal layer especially along with retrograde menstruation in the intra abdominal or the myometrial region. In this study, 46 paraffin blocks of endometriosis and 50 paraffin blocks of normal endometrium as a control were selected. After extracting DNA, all samples were examined for the presence of beta globin gene and suitable samples searched for the presence of L1 HPV-Common by polymerase chain reaction (PCR). HPV was detected by PCR in 11 of 43 (58/25%) cases of endometriosis tissue samples and 7 of 43 (27/16%), endometrial samples. A total of 18 out of 86 samples (93/20) were positive by using general primers of HPV. HPV infection in endometriosis lesions as well as control tissues supports the spread of the virus or HPV-infected endometrial cells via retrograde menstruation. Due to an association of HPV in carcinomas, we propose that persistent HPV infection of endometriosis lesions could contribute to malignant progression.

Background and Ôvarian tumour is a common neoplasm of the female genital tract and one of the most lethal gynecologic malignancies. The aetiology of ovarian cancer remains unclear. Ôncogenic viruses can contribute to different steps of the carcinogenic process. Papillomaviruses are Ôncogenic virus that can be induce proliferation of epithelial cells. Ïn this study, were selected Paraffin-embedded blokes from 50 female patients with ovarian carcinoma and 58 ovarian tissues (without malignancy) as a control. Âfter DNÂ extraction, Âll samples were analyzed for the presence of beta globin gene and suitable samples were screened for existence of L1 HPV-Çommon. Âll samples that were positive for beta globin gene, to amplify by HPV-common primers. 7 out of 44 (15.90%) Ôvarian carcinoma and 5 out of 50 (10%) ovarian tissue were positive for the common marker of HPV. Ïn overall samples, 12 out of 94 (12.76%) samples were positive. Statistically, the correlation between HPV infection and ovarian cancer (P = 0.397) wasn’t significant. Çonclusion: No significant correlation between HPV infection and ovarian cancer was found (P>0.05).Ôur data couldn’t confirm a role of HPV in ovarian cancer.

Male breast carcinoma (MBC) is an unusual form of neoplasia, representing 0.7 to 1 percent of all breast cancer cases. Usually, the carcinoma affects patients after the sixth decade. The aim of this study was to evaluate the status of estrogen and progesterone receptors (ER and PR) and prognostic factors (p53 and Her-2/neu) in a series of male patients with breast cancer and correlate them with tumor grade and stage. Fifty cases of breast carcinoma in male patients, retrieved from the files of the Cancer Institute from 1996 until 2005 was included in this study. Most of the cases were categorized as grade 2 (65.3%), grade 1 cases comprised 20.4% and grade 3 was 14.3%. Stage IIb was the largest group (32%). Estrogen receptor was detected in 90% of cases and progesterone receptor in 68% of cases and no significant correlation was found between estrogen and progesterone receptor positivity and tumor grade or stage. In addition, p53 and Her-2/ neu staining revealed positivity in 11 cases (27.5%) and 13 cases (26%) respectively with strong positivity in only 6 cases and no significant correlation was found between tumor grade and stage and p53 expression. It is clear from our data that Her-2/neu positivity in MBC is lower than in female breast carcinoma. This study, which comprises rather large series of MBC in Iran during a 10-year period, shows that most patients refer in rather late stages and prognostic factors such as p53 and Her-2/neu has no significant correlation with tumor grade and stage at presentation in our patients.