Cholangiocarcinoma: An-eight-year Experience in a Tertiary-Center in Iran

Mohammad-Alizadeh, Amir Houshang,Ghobakhlou, Mehdi,Shalmani, Hamid Mohaghegh,Zali, Mohammad Reza Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.11

Background and Aim: Cholangiocarcinoma (CCA) is an uncommon malignancy of the bile duct, occurring in nearly 2 out of 100,000 people. It is a type of adenocarcinoma that originates in the mucous glands of the epithelium, or surface layers of the bile ducts. The aim of this study was to evaluate the clinical features, diagnostic results and factors associated with survival, morbidity and mortalityof cholangiocarcinoma cases in Iranian patients. Method: In this retrospective study the hospital medical records of 283 patients with a primary or final diagnosis of cholangiocarcinoma who had been admitted to gastroenterology ward of our hospital from 2004 to 2011 were retrospectively reviewed. Results: 283 patients (180 male, 63%, and 103 female, 38.6%) with a mean age of $59.7{\pm}14.4$ years were studied. The most frequent symptoms were painless jaundice (190, 66.9%), abdominal pain (77, 27%), pruritus 133 (46.8%) and weight loss (169, 59.5%). The most frequent associated risk factors and diseases were as follows: gallstones (72, 25.4%), diabetes (70, 24.6%), HBV infection (52 (18.3%), HCV infection 43 (15%), primary sclerosing cholangitis (16, 5.6%) and smoking (120, 42.3%). The most frequent type of cholangiocarcinoma in ERCP and MRCP was hilar. The mean survival time was $7.42{\pm}5.76$ months. Conclusion: The mean survival time in our study was lower than one year. Moreover the most frequent risk factors and associated diseases were smoking, gallstones and diabetes. Painless jaundice, abdominal pain and weight loss were the most clinical features related to cholangiocarcinoma. Additionally survival time did not correlate with risk factors, associated diseases and clinical presentations, but was linked to biliary metallic stenting and surgery.

Clinical, Laboratory Biomarkers and Imaging Findings of Pancreatic Adenocarcinoma in Iran

Hadizadeh, Mohammad,Padashi, Maryam,Alizadeh, Amir Houshang Mohammad,Zali, Mohammad Reza Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.10

Background: Pancreatic cancer has a high mortality rate because it is usually diagnosed late. Since little is known about this cancer in Iran, with the aim of improving this knowledge deficiency, we evaluated clinical, laboratory biomarkers, imaging findings and treatment modalities in Iranian patients with pancreatic adenocarcinoma. Materials and Methods: 131 cases of pancreatic adenocarcinoma in 2010-2013 were obtained from the Taleghani Hospital Record Department. Cases confirmed by histopathology from CT-guided biopsy, EUS-FNA and surgery examination were included. We excluded those with incomplete medical records. Results: The study included 131 subjects between 24 and 97 years of age and a mean age of $63{\pm}13.4$ years. Eighty (61.1%) were male and 51 (38.9%) female. Previous history included diabetes mellitus in 36 (27.5%), alcohol drinking in 5 (3.9%), smoker in 28 (21.4%) and opium addiction in 13 (10%). The common presenting history included weight loss in 79 (60.3%), abdominal pain in 77 (58.8%), fever in 11 (8.4%), nausea in 30 (22.9%), jaundice in 72 (55%), pruritus in 52 (39.7) and anemia in 33 (25.2%). CA19-9 levels with cut offs of 50, 100 and 200 U/ml were increased in 81%, 72% and 66% of patients, respectively. Tumor staging was: stage I, 3 (2.3%); stage II, 10 (7.6%); stage III, 58 (44.3%); and stage IV, 60 (45.8%). From 45 patients, 17 received ERCP inserted metallic stents and 22 plastic stents, the remaining 6 failed that PTC was done. Whipple surgery and chemotherapy were conducted for 10 and 29 patients, respectively. Conclusions: This disease affected older people and there was a male preponderance. The commonest risk factors were diabetes mellitus, smoking and cholelithiasis. The majority of patients presented with loss of appetite, loss of weight, jaundice, abdominal pain and discomfort. Almost all presented at late stages of the disease so that curative surgery was impossible. Also chemotherapy was only performed in a few patients as a neoadjuant treatment.

Immunogenicity of EIT chimeric protein expressed in transplastomic tobacco plants towards development of an oral vaccine against Escherichia coli O157:H7

Farrokh Karimi,Amir Mousavi,Houshang Alizadeh,Ali Hatef Salmanian,Sima Rafati 한국식물생명공학회 2013 Plant biotechnology reports Vol.7 No.4

Chloroplast genetic engineering offers an opportunity for high level expression and cost-effective recombinant protein production. Escherichia coli O157:H7 is one of the most important zoonotic pathogens causing hemorrhagic colitis (HC) and the life-threatening hemolytic- uremic syndrome in humans worldwide. The occurrence of zoonotic E. coli O157:H7 outbreaks in recent years has led to increased efforts in the development of safe and cost-effective immunogenic antigens against E. coli O157:H7. EspA and Tir/Intimin proteins are the important virulence factors which are encoded by the LEE locus of enterohemorrhagic E. coli. In this study, we hypothesized that the high level expression of the chimeric form of these effectors in chloroplasts and using tobacco transplastomic plants as an oral delivery system for the development of an edible-base vaccine would induce an immune response for the prevention of E. coli 0157:H7 attachment and colonization in animal model mice. The prokaryotic codonoptimizedEIT protein was expressed in plastid genome via chloroplast transformation. Putative transplastomic plants were analyzed by PCR, and Southern blot analysis confirmingchloroplast integration and homoplasmy in the T1 progeny. Immunoblotting and ELISA assays demonstrated that the EIT protein was expressed in chloroplasts and accumulated up to 1.4 % of total soluble protein in leaf tissue. In mice orally immunized with transplastomic tobacco plant leaves, high immunological responses (IgG and IgA specific antibodies) were detected in serum and feces. Finally, the challenging assay with E. coli O157:H7 in immunized mice showed reduced bacterial shedding.

Immunogenicity of EIT chimeric protein expressed in transplastomic tobacco plants towards development of an oral vaccine against Escherichia coli O157:H7

Karimi, Farrokh,Mousavi, Amir,Salmanian, Ali Hatef,Alizadeh, Houshang,Rafati, Sima 한국식물생명공학회 2013 Plant biotechnology reports Vol.7 No.4

Chloroplast genetic engineering offers an opportunity for high level expression and cost-effective recombinant protein production. Escherichia coli O157:H7 is one of the most important zoonotic pathogens causing hemorrhagic colitis (HC) and the life-threatening hemolytic-uremic syndrome in humans worldwide. The occurrence of zoonotic E. coli O157:H7 outbreaks in recent years has led to increased efforts in the development of safe and cost-effective immunogenic antigens against E. coli O157:H7. EspA and Tir/Intimin proteins are the important virulence factors which are encoded by the LEE locus of enterohemorrhagic E. coli. In this study, we hypothesized that the high level expression of the chimeric form of these effectors in chloroplasts and using tobacco transplastomic plants as an oral delivery system for the development of an edible-base vaccine would induce an immune response for the prevention of E. coli 0157:H7 attachment and colonization in animal model mice. The prokaryotic codonoptimized EIT protein was expressed in plastid genome via chloroplast transformation. Putative transplastomic plants were analyzed by PCR, and Southern blot analysis confirming chloroplast integration and homoplasmy in the T1 progeny. Immunoblotting and ELISA assays demonstrated that the EIT protein was expressed in chloroplasts and accumulated up to 1.4 % of total soluble protein in leaf tissue. In mice orally immunized with transplastomic tobacco plant leaves, high immunological responses (IgG and IgA specific antibodies) were detected in serum and feces. Finally, the challenging assay with E. coli O157:H7 in immunized mice showed reduced bacterial shedding.

Diagnosis of Malignant Biliary Strictures: Conventional or Negative Pressure Brush Cytology?

Abbasi, Mohammad Reza,Mirsaeed, Seyedeh Masoumeh Ghazi,Alizadeh, Amir Houshang Mohammad Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.10

Background/Objective: The aim of this study was to perform a comparative evaluation of the yields of conventional brush cytology and brush cytology with negative pressure in the diagnosis of malignant biliary strictures. Methods: A total of 132 consecutive patients undergoing endoscopic were identified. Of these, 88.0 had brush cytology after ERCP and 44 were Brush cytology with negative pressure. Retrograde cholangiopancreatography (ERCP) including brush cytology and brush cytology with negative pressure in patients with biliary strictures between 2012-2015. Endoscopic retrograde cholangiography was performed with a standard videoduodenoscope Olympus TFJ 160-R (Olympus, Hamburg, Germany) and brush cytology with a Cook medical Double Lumen Biliary BrushTM (Cytology). Means and standard frequencies were used to calculate variables. Results: Positive results for malignancy were obtained in 22 of 88 patients (25%) by brush cytology and 31 of 44 patients (70.4 %) by brush cytology with negative pressure. Conclusions: Sensitivity of cytology sampling could be maximized by negative pressure during ERCP.

Risk Factors for Post-ERCP Cholangitis in Patients with Pancreatic Cancer from a Single Referral Center in Iran

Salehimarzijarani, Babak,Dadvar, Zohreh,Mousavi, Mirhadi,Mirsattari, Dariush,Zali, Mohammad Reza,Alizadeh, Amir Houshang Mohammad Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4

Cholangitis is relatively uncommon but associated mortality is high due to the predisposition in people with underlying disease. For this recognition of contributing risk factors is necessary. Therefore, the present descriptive-analytical cross-sectional survey was designed to determine contributing risk factors for post-ERCP cholangitis in patients with pancreatic cancer. From 2005 to 2010, 110 consecutive cases of pancreatic cancer attending to a tertiary referral centre (Taleghani Hospital), Tehran, Iran were recruited. The patients all underwent stenting via endoscopic retrograde cholangiopancreatography (ERCP). On univariate analysis, a metallic stent type (95% confidence interval (CI) 1.025-11.34, P=0.037), having no jaundice (1.44-2.22, P=0.009), having no pain (1.32-1.91, P=0.026), a history of prior ERCP (1.16-10.37, P=0.020), and having a proximal biliary stone (1.002-5.93, P=0.046) were related to cholangitis. However on multivariate analysis, none of these factors were found to be contributing risk factors. Cholangitis is avoidable with adequate biliary drainage. Because success rates are higher and complication rates lower for endoscopists performing large volumes of ERCP, performance of the procedure should be concentrated as much as possible in institutions with endoscopists having adequate experience. Patients with a high risk for complications may be best served by referral to an advanced center.

Role of Endoscopic Ultrasound in Evaluation of Pancreatic Neuroendocrine Tumors - Report of 22 Cases from a Tertiary Center in Iran

Haghighi, Shirin,Molaei, Mahsa,Foroughi, Forough,Foroutan, Mojgan,Dabiri, Reza,Habibi, Effat,Alizadeh, Amir Houshang Mohammad Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.9

Background: The pancreatic neuroendocrine tumor (pNET) is relatively rare and generally felt to follow an indolent course. EUS has an important role in detection of pNET. This is a review of clinical and radiological presentation and pathologic reports of 22 patients with pNET. Patients and methods: In this study we analyzed clinical and radiological presentations and pathologic reports of all relevant cases who were referred to Taleghani hospital for 3 years since 2008. Results: A total of 22 patients 28-74 years old (mean=49) were enrolled between 2008 and 2011. Among the total, 13 (59%) were male, 9 (41%) were female and 16 (72.7%) had functional tumors. The results of CT were negative in 12 (54%) cases but EUS was capable of detecting the lesions in these patients, cysts being found in 4 (19%) patients. Conclusion: EUS is a highly sensitive procedure for the localization of functional pNETs and especially insulinomas. Nonfunctional tumors were detected in more advanced and late stages and cystic lesions were more common in this group.

Hijacking Tobacco Hairy Roots and Leaves in Order to Produce IpaD Antigen by Means of Different Signal Peptides

Shahram Shokrian Hajibehzad,Fariba Abooei Mehrizi,Hossein Honari,Houshang Alizadeh 한국작물학회 2017 Journal of crop science and biotechnology Vol.20 No.5

IpaA, IpaB, IpaC, and IpaD are Shigella dysenteriae Ipa operon genes which collectively contribute in invasion to the epithelial cells of the human gut. Among them, IpaD has been demonstrated to play the most crucial role in shigellosis. Noteworthy, due to the more efficient, cost-effective and no need for advanced equipment in comparison with traditional systems, plant-based expression systems are considered as a novel strategy for production of recombinant proteins. As an aim of this research, attempts were carried out to examine and compare IpaD antigen production in three different plant-based platforms, including transgenic tobacco hairy roots and leaves as well as a transient based expression. Furthermore, different signal peptides (i.e. Zera and Extensin) were also employed in order to improve the production level. Based on TAS-ELISA result, the highest yield of IpaD acquired by ER-derived protein bodies (Zera ) which was more than 1.29-fold higher as compared with apoplastic space based on TSP% in both transgenic tobacco hairy roots and leaves. Furthermore, transgenic tobacco hairy roots were more abundant than transgenic leaves averaging 0.52 ng of IpaD per μg TSP and with a maximum of 0.94 ng IpaD per μg TSP in the best-performing construct of pBI-ZeCIpaD. Totally, the results of quantitative RT-PCR and TAS-ELISA indicated that the best time point for the production of IpaD using agroinfiltration was 72 h post infiltration and during 72 to 96 hpi, expression levels descended rapidly. To the best of our knowledge, this is the first report representing and combining the potential effects of signal peptides and plant-based expression platforms on stably production of IpaD antigen in transgenic tobacco leaves and hairy roots.