مجله دانشکده پزشکی دانشگاه علوم پزشکی تهران
سال شصت و نهم شماره 9 (پیاپی 129، آذر 1390)

Human cancer cell lines express human choriogonadotropin (hCG), its subunits and derivatives, regardless of their origin and type. It appears that hCG is a common phenotype in human cancer cell lines. In this research, the effects of hCG targeting monoclonal antibodies (7D9, T18H7 and T8B12) on human cancer cell lines were evaluated. Monoclonal antibody secreting hybridomas were proliferated and injected intraperitoneally to Balb/C mice after treatment with pristine. Two weeks later, ascites fluid was collected. Purification of aforementioned antibodies from ascites fluid was performed using G-protein affinity followed by ion exchange chromatography. SDS-PAGE and ELISA confirmed the structure and functional integrity of the purified antibodies, respectively. Two human cancer cell lines "Hela" and "MDA" were treated by the purified antibodies. Three days later, different wells were imaged and the cells counted. SDS-PAGE gel (None-reducing) indicated consistency of band migration patterns with control antibodies. ELISA test using hCG antigens indicated that the produced antibodies could detect hCG antigens. Cell lines were cultured and treated with different concentrations of each antibody. Counting and imaging different wells of treated plates, indicated that 7D9 antibody had a more significant (P<0.01) cytotoxic effect on cancer cell lines than the control cells. HCG targeting monoclonal antibodies can be used for targeted cancer therapy, as human cancer cells express hCG gene. 7D9 antibody that exhibits protease activity is a proper candidate for this purpose, as it possesses both antagonistic and enzymatic properties.

Aldehyde dehydrogenase 1 (ALDH1) is a marker of normal and malignant human mammary stem cells that has been reported to be associated with poor prognosis. Studies on the detection of ALDH1+ cells can help the treatment of patients with breast cancer. The aim of this study was to determine the activity of ALDH1 in breast cancer and its relationship with the pathological features of the tumors. ALDH1 activity was studied by immunohistochemistry in 121 paraffin-embedded histological samples of breast cancer patients from Department of Pathology of Milad Hospital, Tehran, Iran during 2006-2007. The relationship of ALDH1 with the pathological features of the tumors (size, grade, lymph node metastasis and vascular invasion) was also investigated. Eighty-five percent of breast cancer samples expressed ALDH1 in their cytoplasm with a wide range of intensity (weak, moderate and strong), while 18 samples (14.9%) were completely negative. The majority of cases (97.1%) showed ALDH1 positivity in the stroma of tumors which varied from weak (2.9%) to strong (73.5%). ALDH1 H-score (ALDH1% × intensity) of tumor cells varied from 0 to 240 (mean= 80). ALDH1 H-score was ≤80 in 62 (51.2%) and >80 in 59 (48.8%) samples. There was no statistically significant relationship between ALDH1 H-score and age (P=0.358), tumor size (P=0.375), tumor grade (P=0.207), lymph node metastasis (P=0.125) or vascular invasion (P=0.190). ALDH1 activity was demonstrated in 85.1% of breast cancer samples although its level of expression was not correlated with the pathologic features of breast tumors.

Cyclooxygenase 2 is a key enzyme which converts arachidonic acid into prostaglandins. Cyclooxygenase 2 is triggered by inflammatory stimuli, such as cytokines. Its expression increases in tumors and Alzheimer's disease and ovarian hyperstimulation syndrome. Polycystic ovarian syndrome is a heterogeneous disease characterized by pathological angiogenesis and chronic anovulation. In the present study, the probable role of cyclooxygenase 2 in Wistar rats with polycystic ovarian syndrome was investigated. Thirty female Wistar rats (170-200 gr) were equally divided into three groups: 2 mg estradiol valerate was intramuscularly administered to each rat in the experiment group or group 1; the rats in group 2 were regarded as the sham group and received sesame oil injections and group 3 or the control group received no injections. After 60 days of treatment, animals were anaesthetized with chloroform and killed by decapitation. Ovaries were collected for histological and immunohistochemical evaluations. All the experiments were repeated three times. Morphologically, ovaries from the control group exhibited follicles in various stages of development and many fresh corpus luteum. In estradiol valerate group small follicles in early development were observed in addition to follicles showing evidence of atresia and many large cysts with thickened theca cell layer. Corpus luteum was rare or absent in group 2. The immunohistochemical analysis for cyclooxygenase 2 expression showed an increased expression of cyclooxygenase 2 enzyme in group 1. The results suggested the involvement of cyclooxygenase 2 in the progression to polycystic ovarian syndrome in a rat model.

More than 80 years, the standard treatment of locally advanced cervical cancer was radiotherapy. However, based on several phase III randomized clinical trials in the past decade, concurrent cisplatin-based chemoradiotherapy is the current standard of treatment for this disease. Gemcitabine has potent radiosensitizing properties in preclinical and clinical trials, so it can be utilized simultaneously with radiation. Thirty Women with untreated invasive squamous-cell carcinoma of the cervix of stage IIB to stage IVA were enrolled in the study in Radiation Oncology department of Imam Khomeini Hospital in Tehran from September 2009 to September 2010. Sixty mg/m2 gemcitabine followed by 35 mg/m2 cisplatin were concurrently administered with radiotherapy to the whole pelvic region on day one of each treatment week for five weeks One and three months after treatment, patients underwent a complete physical examination and MRI to determine the response to treatment. The mean age of the participants was 58.13±11.83 (29-78) years. After 3 months of treatment, 73.3% had complete and 26.7% had partial response to treatment. Grade 3 anemia was seen in 10%, grade 3 thrombocytopenia in 3.3% and grade 3 leukopenia in 10% of the patients. According to the positive results of this study in stage IIB, further phase II and III clinical trials are suggested to evaluate the role of chemoradiation by gemcitabine in advanced cervical cancers.

Anterior cruciate ligament (ACL) reconstruction is a first choice treatment for ACL-deficient knees, and arthroscopic single-bundle reconstruction has been widely accepted around the world in this regard. Although, such single-bundle reconstructions result in sufficient knee stability in most cases, but some patients have not been satisfied with postsurgical results in both short-term and long term clinical studies. One of the reasons for these unsatisfactory results could be related to the fact that normal function of the native ACL has not been restored by the traditional ACL reconstruction which uses only a single-bundle graft. The natural ACL consists of a 3-dimensional structure with multibundle fascicles, which can be anatomically divided into 2 main bundles, the anteromedial (AM) and the posterolateral (PL) bundles named for the orientation of their tibial insertions. The purpose of the present study was to compare double-bundle and single-bundle ACL reconstruction. Twenty-two patients with anterior cruciate ligament tear who were candidates for ACL reconstruction were enrolled in the study undertaken in Shariati Hospital from 2009 to 2010. Fourteen patients underwent single-bundle and 8 patients double-bundle ACL reconstruction. The patients were evaluated by arthrometer and physical examination in postoperation follow up visit at least 9 months after the operations. Four out of 14 patients with single-bundle reconstruction had knee joint translation greater than 5 mm but nobody had knee translation more than 5 mm in the double-bundle reconstruction group. Double-bundle ACL reconstruction seems to be more stable than single-bundle ACL reconstruction.

Breast cancer is the most common form of hereditary cancer worldwide and is an important cause of morbidity and mortality. Approximately 5-10% of breast and ovarian cancers are due to the highly penetrating germline mutations in cancer predisposing genes. Two genes, BRCA1 and BRCA2, account for at least half of these cases. The demand for BRCA1 and BRCA2 mutation screening is rapidly increasing as their identification will affect the medical management of people at increased risk for the disease. Therefore, the aim of this study was to investigate BRCA1/2 mutations in 100 high risk Iranian families. One hundred families who met the minimal risk factors for breast/ovarian cancer were screened among the families referred to Kawsar Human Genetics Research Center for the diseases in 2009-2011. The entire coding sequences and each intron/exon boundaries of BRCA1/2 genes were screened for by direct sequencing and MLPA in both patients and the controls. In the present study, we could detect the following novel mutations: p.Gly1140Ser, p.Ile26Val, p.Leu1418X, p.Glu23Gln, p.Leu3X, p.Asn1403His, p.Asn1403Asp, p.Lys581X, p.Pro938Arg, p.Thr77Arg, p.Leu6Val, p.Arg7Cys, p.Leu15Ile, p.Ser177Thr, IVS7+83(-TT), IVS8 -70(-CATT), IVS2+9(G>C), IVS1-20(G>A), IVS1-8(A>G), p.Met1Ile, IVS2+24(A>G), IVS5-8 (A>G), IVS2(35-39)TTcctatGAT, IVS13+9 G>C in BRCA1 and p.Glu1391Gly, p. Val1852Ile, IVS6-70(T>G), 1994-1995 (InsA) in BRCA2. Ten mutations seemed to be pathogenic and the disease-causing mutations were seen in 16% of the families. In addition, from the total number of substitutions and reassortments (42), 80% related to BRCA1 and 20% to mutations in BRCA2 genes.

Left main coronary artery (LMCA) stenosis is a leading cause of mortality and morbidity in many countries. Metabolic syndrome (MS) is a risk factor for coronary artery disease (CAD). The effects of MS on left main coronary artery stenosis are not well-defined. The aim of this study was to examine the effects of MS on left main coronary artery stenosis. A total number of 495 patients who underwent elective coronary angiography in the Catheter Laboratory of Cardiovascular in Shariati Hospital 2008-2010 were included in the study. MS definition was based on the National Cholesterol Education Program (NCEP)- Adult Treatment Panel III (ATP III) criteria. The stenosis in left main coronary arteries was determined by examining the coronary angiograms of the patients. The study population consisted of 249 (50.3%) men, and 246 (49.7%) women. The mean age of the participants was 58.01±10 years. MS was present in 86 (17.4%) of the patients based on NCEP- ATP III criteria. LMCA stenosis was seen in 25 (5%) patients. A positive correlation was found between MS and LMCA stenosis (r=0.305, P=0.012). Moreover, a positive correlation was found between age (r=0.192, P=0.05), sex (r=0.334, P=0.007), smoking (r=0.336, P=0.01) and diabetes (r=0.253, P=0.03) and LMCA stenosis. The metabolic syndrome correlates with LMCA stenosis. LMCA stenosis and its correlation with MS is precipitated by high FBG, age, male sex, and smoking which may synergistically increase the risk for the disease.

Too many studies are in the process of determining the probable role of immune system in the etiopathogenesis of nasal polyposis. This study was designed to identify the probable participation of Th1, Th2 lymphocytes in the induction and progression of nasal polyposis. Seventy-five patients, 42 male and 33 female, with nasal polyposis were examined for total serum IgE, specific serum IgE and reaction to skin test for differentiating allergic from non-allergic participants in Rasoul Akram Hospital during 2010. To determine the possible correlation of allergic reactions in the upper respiratory tract and nasal polyposis, cytokine gene expression was evaluated on the extracted RNA by RT-PCR. The data were analyzed by using c2, independent t-test, correlation and Receiver operating characteristic (ROC) curve. The mean age of participants was 38 years (18-81 years). IFN-γ and IL-4 gene expressions were more prevalent in allergic than non-allergic individuals (IFN-γ: 39.5% vs. 14.2%, P=0.3 and IL-4: 44.7% vs. 18.9%, P=0.02, respectively). IL-10 and IL-12 (P35 and P40 fractions) genes were not significantly different between the two groups. IL-10 and IL-12 (P35, P40) genes did not differ significantly either. This research suggests that overproduction of cytokines and an imbalance of Th1 and Th2 cell production may play an important role in the pathophysiology of allergic or non-allergic nasal polyp formation. Thus, although nasal polyposis is a multifactorial disease with several different etiological factors, chronic persistent inflammation is undoubtedly a major factor irrespective of the etiology.

Nocardiosis is a rare and potentially life-threatening infection caused by several species of the Nocardia genus. The objective of this study was to develop and evaluate a rapid and new method to clinically identify relevant Nocardia species. Rapid and accurate diagnosis of Nocardia species is essential for the treatment of severe infections and prevention of cerebral abscess.

One hundred and eighty patients, 103 (57.22%) male and 77 (42.78%) female, with severe symptomatic pulmonary infection were studied in the course of a 12-month period in Dr. Shariati Teaching Hospital affiliated to Tehran University of Medical Sciences in 2010. The specimens were cultured and identified using microbiological and biochemical tests. Polymerase chain reaction (PCR) was used to directly identify the organism in the broncoalveolar lavage samples collected from the patients. NG1 and NG2 primers were used to amplify a Nocardia genus-specific 598-bp fragment of 16S rRNA.

Nineteen samples (10.56%) were positive with PCR and 5 samples (2.78%) with conventional methods. All samples with positive cultures were also positive by PCR.

The results of this study showed that PCR has a high sensitivity and accuracy for the detection of Nocardia compared with culture and biochemical tests. Considering the rapidity, precision, high sensitivity and specificity of molecular techniques, use of these techniques is suggested in conjunction with conventional methods for the detection of Nocardia phenotypes in clinical laboratories and research centers.

The aim of this study was to evaluate the mid-term outcomes of concurrent total correction of Tetralogy of Fallot (TOF) after pulmonary valve (PV) replacement and its relation to QRS duration and MRI results. In this study, 51 patients with TOF who had the TOF surgery and PV replacement enrolled the study. Demographic data, MRI results such as, right ventricular end diastolic volume, right ventricular end systolic volume, systolic and diastolic indexes noted. Moreover, QRS duration and the patient's cardiac functional class were evaluated immediately before and 6 months after the surgery. From 51 patients, 27.5% were female and 72.5% were male. The mean age of participants was 23.48 (SD=5.82) years. Functional class changes were statistically different (P<0.001) comparing the status before and after the surgery. The mean QRS duration before surgery was 130.20 (SD=16.89) ms which was in significant contrast with post-surgical states, 122.45 (SD=16.90) ms (P<0.001). Mean QRS duration before and after surgery was statistically lower in asymptomatic patients (P=0.028 and P=0.025, respectively). There was a statistical relationship between pre-surgical systolic and diastolic indexes to post-surgical functional class as asymptomatic patients had lower systolic and diastolic indexes (P=0.005 and P=0.028, respectively). This study demonstrated that QRS duration before and after surgery can be an indicator to evaluate the cardiac function after surgery for Tetralogy of Fallot. Moreover, systolic and diastolic indexes are factors affecting the good prognosis of patients; therefore, PVR surgery needs to be done before the deterioration of systolic and diastolic indexes and cardiomegaly.