Archives of Iranian Medicine
Volume:17 Issue: 4, Apr 2014

Iran was engaged in the Program of Action for Cancer Therapy (PACT) in 2012, and delegates from the International Atomic Energy Agency (IAEA), and the World Health Organization (WHO) evaluated the National Cancer Control Program (NCCP) status (the imPACT mission), based on which they provided recommendations for improvements of NCCP in the I.R. of Iran. We reported the results of this situational analysis and discussed the recommendations and their implication in the promotion of NCCP in the I.R. of Iran. International delegates visited the I.R. of Iran and evaluated different aspects and capacities of NCCP in Iran. In addition, a Farsi version of the WHO/IAEA self-assessment tool was completed by local experts and stakeholders, including experts from different departments of the Ministry of Health and Medical Education (MOHME) and representatives from the National Cancer Research Network (NCRN). Following these evaluations, the PACT office provided recommendations for improving the NCCP in Iran. Almost all the recommendations were endorsed by MOHME. The PACT program provided 31 recommendations for improvement of NCCP in Iran in six categories, including planning, cancer registration and information, prevention, early detection, diagnosis and treatment, and palliative care. The most important recommendation was to establish a strong, multi-sectoral NCCP committee and develop an updated national cancer control program. The imPACT mission report provided a comprehensive view about the NCCP status in Iran. An appropriate response to these recommendations and filing the observed gaps will improve the NCCP status in the I.R. of Iran.

There is still contradictory evidence on disclosure preferences regarding cancer diagnosis. The aim of this study was to evaluate the preference of cancer patients for knowing the truth about their disease, as well as the factors that might have an impact on these preferences. This study was conducted in 11 cancer centers in Iran. A questionnaire was used to collect data, and all patients above 15 years of age who were willing to participate were included in the study. The patients were asked if they were aware of the malignant nature of their disease, and if they came to know about their disease at the time of initial diagnosis, or later. The patients were then asked about the way they looked upon their disease. In the final part of the questionnaire, the participants were asked the level of involvement they prefer to have in making treatment decisions. In total, 1226 patients were enrolled in this study, only 565 (46.7%) of whom were aware of their disease at the time of diagnosis, and 878 (72.7%) at the time of interview, while 980 (85.2%) were willing to receive information about their disease. Patients’ awareness was significantly associated with age under 50 years, female gender, having breast, skin or head and neck cancer, and having medical care in Shiraz or Hamadan while it was not associated with the stage or accompanying illness. While the majority of Iranian cancer patients prefer to be aware of the nature of their disease and have an active role in treatment decision making, they do not receive this information.

Breast cancer is the most common cancer among women. Mammography screening has been used in many countries to reduce early deaths caused by breast cancer. It is important to ensure that screening programs are effective and efficient. We conducted a study to assess the cost-effectiveness of a national breast cancer screening program implemented in Iran. The perspective of the present study was the health system. Over 26,000 women aged 35 and higher, of low socioeconomic background were recruited from ten cities in the program. We used case-finding as the outcome indicator for assessing effectiveness of the program. We measured the service provision costs, the coordination costs and supervision costs of the program that included the staff costs, and measured cost per detected case. We also conducted sensitivity analyses and calculated false-positive rates as a result of the screening program. The total cost of breast cancer screening program was estimated at $377,797. The program resulted in the identification of 24 patients with breast cancers, not different from baseline expectations without a screening program. The cost per cancer detected was calculated $15,742. The minimum and maximum cost per breast cancer detected were about $13,524 and $16,947, respectively. We observed a false-positive rate of 7.5% among the target population. Our findings suggest that the mammography screening program was not cost-effective. Although there were technical efficiency issues in the conduct of the program, the findings do not support the implementation of national mammography screening programs in Iran in women aged less than 50 years. Careful studies of such programs for higher age groups are also recommended before they are rolled-out nationally.

Esophageal squamous cell carcinoma (ESCC) is a major health problem in many developing countries including Iran. ESCC has a very poor prognosis, largely due to late diagnosis. As a first step in developing an early detection and treatment program, we conducted a population-based endoscopic screening for ESCC and its precursor lesion, esophageal squamous dysplasia (ESD) in asymptomatic adults from Golestan Province, northern Iran, a high-risk area for ESCC, to evaluate the feasibility of such a program and to document the prevalence and risk factor correlates of ESD. This cross-sectional study was conducted among participants of the Golestan Cohort Study (GCS), a population-based cohort of 50,000 adults in eastern Golestan Province. Randomly selected GCS participants were invited by telephone. Those who accepted were referred to a central endoscopy clinic. Eligible subjects were consented and then asked to fill in a brief questionnaire. Detailed information about selected risk factors was obtained from the GCS main database. Endoscopic examination with Lugol’s iodine staining was performed, biopsies were taken from unstained lesions as well as the normally stained mucosa of the esophagus, and the biopsies were diagnosed by expert pathologists according to previously described criteria. In total, 1906 GCS subjects were invited, of whom only 302 subjects (15.8%) were successfully enrolled. Esophagitis (29.5%) and ESD (6.0%) were the most common pathological diagnoses. Turkmen ethnicity (adjusted OR = 8.61; 95%CI: 2.48-29.83), being older than the median age (OR = 7.7; 95% CI: 1.99–29.87), and using deep frying cooking methods (OR = 4.65; 95%CI: 1.19-18.22) were the strongest predictors for ESD. There were significant relationships between esophagitis and smoking (p-value<0.001), drinking hot tea (P value = 0.02) and lack of education (P value = 0.004). We observed a low rate for participation in endoscopic screening. Overall prevalence of ESD was 6.0%. Developing non-endoscopic primary screening methods and screening individuals with one or more risk factors may improve these rates.

Oral cancer is the most common malignant tumor among head and neck cancers. Delay in diagnosis affects the treatment and prognosis of oral cancer. We measured the professional delay in the diagnosis and its attributes in the Cancer Institute of Iran, the largest referral center for oral cancer patients in the country. We interviewed oral cancer patients to measure the delay and used case-control approach to study association of various prognostic factors with professional delay and tumor stage. Out of 206 patients, 71.4% were diagnosed at the advanced stage. The median of the patient, professional and total delays were 45, 86 and 140 day, receptively. In the univariate model, prescription of medicines like analgesics (OR = 5.3, 95% CI 2.2–12.9) and history of dental procedure (OR=6.8, 95% CI 1.7–26.9) were associated with higher risk of delay compared to patient who were biopsied from the beginning. History of loose teeth increased risk of delay 4 times (OR = 4.0, 95% CI 1.6–9.8). Patients with primary education had 70% lower risk of delay compared to the illiterate patients (OR = 0.3, 95% CI 0.1–0.7) and the risk was lower among patients who had diploma (OR = 0.04, 95% CI 0–0.7) and college education (OR = 0.1, 95% CI 0–0.4). The delayed patients were diagnosed in more advanced stage compared to the patients without delay (OR = 2.1, 95% CI 1.0–4.4). Development of a national guideline for follow-up of oral lesions, training and awareness of health care professionals about oral cancer diagnosis may decrease the delay and improve the oral cancer outcome in Iran.

FLT3 ITD and D835 mutations occur in high frequency in AML and to a lower rate in ALL patients with poor prognosis. ITD and D835 mutations were studied in 100 diagnosed acute leukemia patients including 27 AML and 73 ALL with various FAB classifications by PCR and PCR-RFLP, respectively. Subsequently, PCR products of positive samples were confirmed by sequencing analyses. ITD mutations occurred in 10% of all pediatric acute leukemia, including AML and ALL. 25.9% of AML patients harbor a mutation in the ITD in various subtypes. The frequency of ITD mutations was 4% in ALL. Various insertions of nucleotides in ITD were observed, similar to those described in the literature previously. These preliminary data suggest that flt3-ITD mutations may play an important role in leukemogenesis in a proportion of children, particularly in the case of AML.

Meningioma is one of the most common central nervous system tumors derived from meningothelial (arachnoid cap) cells. This paper identiied the network-based Protein-Protein Interactions (PPI) for meningioma compared to healthy controls. Gene expression data, including 384 gene or protein names, were extracted from a number of previous investigations. Out of these 384 proteins, 176 were found to be exclusively expressed in meningiomas and 208 proteins were down-regulated. The networks of related differentially expressed genes were explored using cytoscape and the PPI analysis methods such as MCODE and ClueGO. Analysis introduced a number of hub proteins and 27 clusters (protein complex) with distinctive seed genes. Identiied ClueGO Pathways based on subnetworks mined by MCODE was composed of positive regulation in RBC homeostasis, dysregulation of transport from ER to Golgi, disruption regulation of cell cycle and antigen processing and presentation of exogenous peptide antigen and neutraliza- tion of exogenous dsRNA. Combination of over-expression of TCEA1, UBE2E1, XRCC5, IFIT1, IFIT-3, MCM2, and MCM7 and under- expression of CDC25A, SEC31A, and CDK6 can serve as a diagnostic biomarker panel for meningiomas. These proposed network-based biomarkers for the meningioma patterns may be helpful in diagnosis, prognosis and treat- ment processes, although biomarker validation is necessary.

Cervical cancer is the seventh most common malignancy in both genders combined and the third most common cancer in women. Despite significant progress in treatments, cervical cancer is not completely curable. Therefore, further research is necessary in this area. Animal models are one of the most practical tools in the field of cancer research. The present study aimed to characterize the growth behavior and surface markers of HeLa cells after heterotopic and systemic inoculation to athymic nude mice. Ten 6-week old female athymic C57BL/6 nude mice were used in this study. HeLa cells were inoculated into the flank or tail vein. The tumor volume was calculated and growth curves were drawn. Tumor-bearing mice were sacrificed and the lesions obtained after harvesting were analyzed in a pathology lab. Subsequently, one slide per tumor was stained with hematoxylin and eosin (H&E) and other slides were stained immunohistochemically by cytokeratins (CK), vimentin, P53, CD34, and Ki-67. Tumor take rate, mean doubling time and latency period were 94.4%, 5.29 ± 3.57 days and 15.27 days, respectively. H&E results revealed highly malignant hyperchromatin epithelial cells. Immunohistochemical examination of the heterotopic tumors indicated greater expression of CK and less expression of vimentin compared to the metastatic ones. Sixty percent of cells were P53-positive and more than 80% were Ki-67-positive. CD34 expression indicated the intensity of angiogenesis in tumor. This study represents a comprehensive description of a HeLa xenograft model for in vivo investigations, enabling researchers to assess new treatments for cervical cancer.

Ferulago angulata (Apiacea) has been used in Iranian traditional medicine since ancient times and its various health care and pharmacological benefits have been demonstrated recently. In this study, for the first time, we have investigated the effects of F. angulata flower and leaf ethanol extracts on angiogenesis, as the key process in tumor growth, invasion and metastasis. Cytotoxic effects of different concentrations (20–140 µg/mL) of each extract were assessed on human umbilical vein endothelial cells (HUVECs) using neutral red uptake assay. After evaluating the less toxic concentrations (up to 80 µg/mL), we performed three-dimensional angiogenesis, tube formation and migration assays to assess the key properties of HUVECs, including the angiogenesis process, in response to the extracts. Finally, quantitative gene expression analysis of VEGF-A and VEGFR-2, two critical mediators of angiogenesis, was performed using real-time RT-PCR. Both flower and leaf extracts exhibited concentration-dependent inhibition of sprouting, tube formation and migration capacities of HUVECs. For the flower extract, the respective IC50 values were 25.79, 26.52 and 38.92 µg/mL while for the leaf extract, the corresponding IC50 values were 34.18, 41.24 and 28.69 µg/mL. Both flower and leaf extracts downregulated VEGF-A and VEGFR-2 genes relative to the GAPDH gene as the internal control at concentrations of 60 and 80 µg/mL, respectively. These findings suggest that both flower and leaf extracts may contain anti-angiogenic compounds and may have the capacity to be utilized in tumor anti-angiogenic therapy strategies.

Cancers of the upper gastro-intestinal tract (UGIT) comprise esophageal, esophago-gastric junction, stomach and duodenal cancers. Together, these cancers represent over 1.5 million cases and are the cause of about 1.25 million deaths annually. This group of cancers encompasses diseases with marked disparities in etiology, geographic distribution, histopathological features and frequency. Based on histological origin, squamous cell carcinoma of the esophagus (ESCC), which arises through a dysplasia-carcinoma sequence within the squamous mucosa, is a completely different cancer than junction, stomach and duodenal cancers, which develop within glandular epithelia through cascades involving inflammation, metaplasia, dysplasia and carcinoma. At the frontline between these two histological domains, cancers of the esophago-gastric junction constitute a mixed group of glandular tumors including distal esophageal adenocarcinomas and cancers arising within the most proximal part of the stomach - the cardia. Most of UGIT cancers are sporadic, although familial susceptibility genes have been identified for stomach and rare cases of ESCC. We have used the COSMIC database (http://www.sanger.ac.uk/genetics/CGP/cosmic/) to identify genes commonly mutated in UGIT cancers. Regardless of etiology and histopathology, three genes are mutated in at least 5% of UGIT cancers: TP53, CDKN2a and PIK3CA. Another three genes, NFE2L2, PTCH1 and NOTCH1, are mutated in ESCC only. Conversely, genes of the RAS family and of the CDH1/APC/CTNNB1 pathway are mutated only in non-squamous cancers, with differences in mutated genes according to topography. We review the potential functional significance of these observations for understanding mechanisms of UGIT carcinogenesis.,

Intramedullary spinal cord metastases are rare. The majority of these metastases reportedly spread from lung cancer in the cervical region; however, they have been seen to arise from a variety of other primary sources. Here, we report what is, to the best of our knowledge, the first known case of an intramedullary spinal cord metastatic lesion in the conus region arising from primary endometrioid adenocarcinoma.

Abul-Hasan al-Tabari was a 10th century Persian physician born in Tabaristan. He was a creative and innovative physician who avoided emulating treatments without investigating and examining them. Tabari was an encyclopedist and had a holistic view to medicine. Investigation of the views of this great Persian scholar indicated that his scientific and moral characteristics contain: paying adequate attention to philosophy and medical ethics, citing other scholar's works, attention to the necessity of clinical and hospital training, emphasizing indigenous therapy and scientific and responsible treatment with medical faults and discovery of Sarcoptes scabiei. Tabari has written valuable articles on different medical sciences; however, he is especially famous for authoring the al-Mualajat al-Buqratiya (Hippocratic Treatments) - an important medical encyclopedia. Several of Al-Tabari's succeeding scholars and physician have referred to the al-Mualajat al-Buqratiya in their medical articles. The aim of this study is further introduction of this great physician and assessment of his theories and key works.