Tehran University Medical Journal

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: Neck lymph node metastasis has the prognostic role in SCC of the tongue and the importance of the biologic markers in tumor invasion and metastasis has been stated in the medical literature. The aim of this study was to evaluate the relationship between two biomarkers, p53 and EGFR (which had the main role in cell proliferation) and two other biomarkers, CD44 and E-cadherin, in lymph node metastasis.
Methods: In an analytic descriptive study fifty three patients with SCC (Squamous Cell Carcinoma) of the tongue who underwent the resection of tumor and dissection of neck lymph nodes were assessed during the year of 2002-2009. Histological samples from 53 patients were immunohistochemically stained and the analysis of these markers were performed due to clinicopathological variable and metastasis of the neck lymph nodes.
Results: The result showed that among the clinicopathological factors, the relationship between Age (p=0.01), history of having risk factors (p=0.002), clinical lymphadenopathy (p=0.002), the size of the tumor (p=0.001), decreasing of CD44 (p=0.02) and lymph node metastasis of the neck were statistically significant. No significant relationship were found between sex and other biomarkers including p53, EGFR, E-cadherin.
Conclusion: CD44 is an important indicator of prognostic markers that can also be used as an indicator of clinocopathological markers.

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: Gastric adenocarsinoma is the first leading fatal malignancy in Iran. Despite advances in novel therapeutics approaches for gastric cancer (GC) patient, tumor dissemination via blood stream to distant organ is still the major cause of death. Therefore, there is urgent need to establish sensitive methods for early detection of disseminated tumor cells in peripheral blood (PB) and bone marrow (BM) specimens of gastric cancer patients.
Methods: In the present study, we use Carcinoma Embryonic Antigen (CEA) as a tumor marker and Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH) as an internal control to detection and quantification of disseminated tumor cells in PB and BM specimens of affected individuals. Total RNA was extracted from AGS (gastric cancer) cell line and CEA and GAPDH fragments were generated by reverse transcription. The amplified fragments were cloned into pTZ57R/T vector separately. Double cloning of these genes has done into one pTZ57R/T vector. Serial dilution of this recombinant plasmid is used to construct standard curve, each containing a known amount of input copy number. Total RNA was extracted from BP and BM specimens of 35 GC patients. cDNA of the specimens were synthesized by reverse transcription and subjected to Quantitative Real-Time PCR (QRT-PCR).
Results: We developed a highly sensitive and specific quantitative PCR for CEA and GAPDH using Real-Time PCR based on TaqMan technology. CEA mRNA was detected in 23% of PB and 20% of BM specimens. There was no CEA mRNA detecting in control group.
Conclusions: The QRT-PCR for CEA can be a useful technique for detection of micrometastases in the PB and BM specimens of gastric cancer patients.

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: Routine oophorectomy in women with colorectal cancer is under debate, the aim of this study is to determine incidence, clinicopathologic features and prognostic factors of ovarian involvement in primary colorectal cancer (CRC) and to clear the role of prophylactic oophorectomy.
Methods: Data from primary CRC women treated between years 1990 and 2004 were retrieved and clinical and pathologic features of those who had undergone oophorectomy during CRC surgery were reviewed.
Results: One hundred eighty cases (mean age 47.5 years) were included. In 120(66.6%), ovaries were preserved and 60(33.3%) cases underwent bilateral oophorectomy in addition to primary CRC resection. Reasons for oophorectomy were prophylactic in 22(36.6%), abnormal morphology in 35(58.3%), and undetermined in 3(5%) cases. There were five metastatic carcinomas, eight primary ovarian tumors and 47 normal ovaries in pathologic evaluation. No complication directly related to oophorectomy was noted. Patients with ovarian metastases had higher stages of tumor. Ovarian metastases were not related to menstrual status, CRC location, size, differentiation, and mucin production, as well as abnormal morphology of ovary. The global prevalence of ovarian metastasis in CRC was 2.7%, and isolated ovarian metastases occurred in less than half of them. Of 120 women that underwent colectomy alone, eight (6.6%) developed ovarian metastasis during two years of follow-up. Only three cased had isolated ovarian metastases. No patient with synchronous or metachronous ovarian metastases from CRC survived five years.
Conclusion: Isolated ovarian metastases from primary CRC occur with a low frequency and this may partially explain the debate regarding prophylactic oophorectomy at the time of curative resection for primary CRC.

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Cancer is one of the main reasons of mortality worldwide, and more than 90 percent of cancer deaths are due to metastasis. Although primary tumors are curable using chemical adjuvant therapy or surgery, metastatic tumors are mostly incurable. This resistance shows the high rate of mortality among patients with metastatic disease. Being a sequential event, metastasis is a subtle and intricate process in which tumor cells undergo a plenty of changes and acquire the capacity of migration, invasion, survival and self-renewal which all are necessary for metastasis to happen. The key point in recognition and cure in invasive cancers is to identify critical genes, proteins and pathways involved, and show their relation with each other and the disease. Forming metastasis needs favorable genetic and microenvironmental elements of tumor cells and distant tissue, respectively. Unfavorable conditions in each steps of this process lead to arresting metastasis and subsequent dormancy, which is the most important phenomenon in relapse. In this review, benefiting from tens of reliable and recently identified data and personal experiences, it has been tried to draw new patterns associated with metastasis for further investigation. Determining genes, proteins and microenvironmental factors that affect metastasis, in a sequential manner, can help better understanding of this lethal process and subsequently a prosperous treatment.

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Background: Bone is one of the most common sites of metastatic disease in malignancies. Many of the cases are asymptomatic and may be diagnosed in primary or secondary follow-up, but in symptomatic cases pain is the prominent symptom which is mostly exaggerated at nights. The improved survival of cancer patients with bony metastases in recent years, specially in breast and prostate cancer, has given a greater importance to the careful choice of treatments in this setting. This can lead to a better quality of life, lower treatment cost, prevention of disabilities, less delay in primary cancer therapies, and decrease of life-threatening events for the patients. Here we review the metastatic disease of the bone and its treatments, with emphasis on local and systemic radiation therapy. Current literature about bone metastasis and its treatments was reviewed through a search of available databases on internet for papers published in 1995-2013. Special attention was given to the research trials and studies performed by the authors on this setting. Treatment of bone metastases consist of analgesics, radiotherapy, surgery and bisphosphonates. Control of bone metastases is a challenging process, necessitating a multi-disciplinary approach and teamwork between the treating physicians. Radiotherapy is the most useful modality for this purpose in oncology, given both as a local and systemic therapy. We hope that this review would be able to help in choosing the best treatment option for this common palliative situation in Iranian cancer patients.

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Background: Colorectal carcinoma is considering as a curable disease. Treatment of recurrent cases is hard and sometimes impossible. Evaluation of the rate and affecting factors of recurrence in each hospital would help to decreasing recurrent cases. The aim of this study is evaluation of the rate, clinical and pathologic features, and outcome of recurrent colorectal carcinoma in a referral teaching hospital in Tehran. Methods: Clinical data of 166 curative resections of colorectal carcinoma who were operated between Mehr 1384 and Mehr 1388 (between 23 September 2005 and 23 September 2009) in Imam Khomeini Hospital and were accessible for follow up was collected. Follow up data was collected prospectively up to Farvardin 1391 (19 April 2012). Forty nine recurrences were happened in this period. We compared recurrent and non-recurrent cases for different variables Results: Average age of the patients was 53.5 years, and 47% of them were female. The median time to the diagnosis of recurrent disease was 12 months (range 1 months to 54 months). There were no significant differences between recurrent and non-recurrent patients about age, sex, sub-site of the tumor and sub-type of primary operation. Rate of overall recurrence, local recurrence and distant metastasis were 29.5%, 15.7% and 12.1% respectively. Local recurrence rate was higher in colon cancer (16.44% vs. 15.05%) but distant metastasis rate was higher in rectal cancer (12.9% vs. 10/96%). Rate of curative re-resection was about 25%. Overall survival of the recurrent patients who underwent surgery was better than who underwent chemo or radiotherapy (66.7% vs. 56.8%). Median survival time of recurrent patients after primary surgery was 28 months, and after diagnosis was 12 months (9.28- 14.72,95% CI). Conclusion: In this study the rate of overall recurrence was 29.5%. Local recurrence rate was higher in colon cancer (16.44% vs. 15.05%) but distant metastasis rate was higher in rectal cancer (12.9% vs. 10/96%).

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cBackground: Choriocarcinoma is a highly malignant form of gestational trophoblastic disease. It is characterized by metastatic potential, rapid growth and deeply invasion into blood vessel and then widespread dissemination metastasis. However, the most common sites of metastatic choriocarcinoma are lung, vagina, liver, and brain. But, metastatic choriocarcinomas rarely is extended to gastrointestinal system. It is im-portant to keep in mind that despite extensive metastasis, choriocarcinoma is very curable disease. Due to high responsibility of this disease, early diagnosis of choriocarcinoma and treatment with chemotherapy can prevent mortality and morbidity of these patients. In this case report, we present a rare case of metastatic choriocarcinoma in the small bowel after normal term pregnancy. Case Presentation: A 34-years-old woman G4, P4, L4 presented with abnormal postpar-tum vaginal bleeding (45 days) and unresponsive to usual medical and surgical therapy (oxytocine, metergene, antibiotic, and double curettage). The patient was admitted in the Ghaem Hospital, Mashhad University of Medical Sciences in April 2013. She suf-fered from rectal hemorrhage and severe weakness. Because of unsuitable condition (shock), laparotomy was performed and small bowel involvement was observed. Seg-mental resection of small bowel detected metastatic choriocarcinoma of the lesion. We couldn’t rescue our patient due to unresponsive to combination chemotherapy (actino-mycine, methotrexate, cyclophosfamide, vincrystine, etopuside). Conclusion: In abnormal postpartum hemorrhage, we should consider the possibility of choriocarcinoma. Although, it is important to note rare manifestations of metastatic choriocarcinoma of small bowel in massive gastrointestinal hemorrhage.

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Background: Metastasis associated miRNA (metastamiR) opened a new field of anti-metastatic therapy which have a great potential of treatment for the most lethal aspect of cancer, metastasis. The pleiotropic nature of gene regulation exhibited by certain miRNAs that showed that miRNAs might be endowed with a capacity to function as crucial modulators of tumor metastasis. MiR-31 is a pleiotropic anti-metastatic miRNA whose expression decreased significantly in metastatic breast cancer cells. MiR-31 has multiple roles in metastasis cascade. Therefore, using the miR-31-restoration based therapy could be an efficient anti-metastatic strategy for cancer therapy. Methods: This research was performed from May 2014 to October 2015 in Tarbiat Modares University in Tehran, Iran. The double-strand oligo of mature miR-31 was cloned into pcDNA 6.2gw/EmGFP according to the manufacturer instruction. The MDA-MB231, MCF-7 breast cancer cell lines were cultured and their miRNAs have been extracted. The expression of miR-31 has been quantified by Real time-PCR be-fore transfection of construct contained miR-31 into two cell lines and in normal breast cells. Then the constructs contain miR-31 have been transfected in to two cell lines. The expression of miR-31 has been quantified after 48 hours. Scratch and invasion as-say have been carried out for assessing the level of migration and invasion. Results: The result of Real time-PCR before transfection of constructs contained miR-31 have been shown 4 fold and more than 100 fold reduction in expression of miR-31 in MCF-7 and MDA-MB231 respectively in comparison to miR-31 expression in nor-mal breast cells, but after transfection of miR-31 construct to MDA-MB231 the quan-tification of expression showed the significant increase in mir-31 expression and 20 fold reduction in invasive and 10 fold reduction in migratory characteristics of MDA-MB231 in comparison to MCF-7. Conclusion: Metastasis associated miRNA have been represented a promising candi-dates in the field of anti-metastatic therapy and miR-31 as a powerful member of this family can function very effectively in order to inhibit the metastasis and introduce the new possibility of metastasis inhibition.

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Background: Breast cancer is not only considered as the most common cancer in women but also is known as the second cause of death among them. One of the main causes of death in breast cancer patients is metastasis to different organs such as lymph nodes, bones, lung, liver, brain or other parts of the body. Metastasis to genital organs especially uterus is rare and a few cases are reported. Case Presentation: In this report we present a case of invasive ductal breast carcinoma metastasizing to a uterine leiomyoma in a 52 year old woman who was admitted to Imam Khomeini Hospital, Tehran, in September 2013, diagnosed and treated by modified radical mastectomy of the right breast six years ago. Currently, she presented with complaint of persistent abnormal uterine bleeding for which hysterectomy was performed. The histopathologic examination of the uterine specimen revealed a focus in the myometrial wall composed of spindle cell proliferation without signs of atypia which was accompanied by epithelial glandular structures with cells containing hypochromatic nuclei embedded in a desmoplastic stroma. Considering the history of invasive ductal breast carcinoma in this patient, the diagnosis of stromal nodule or metastasis from a breast origin was suggested as the main differential diagnosis. The Immunohistochemical study performed with different markers showed positivity for GCDFP15 staining confirming metastasis from the breast carcinoma. Conclusion: Although metastasis of breast cancer to the genital organs is an uncommon event, breast carcinoma is still considered the second source of extragenital malignant metastasis to the uterus. Overall, the most popular sites for metastasis of breast carcinoma to the female reproductive system include the ovaries and the uterine cervix. The uterine corpus is the least common site involved. In this regard metastasis to a uterine leiomyoma is a rare event.

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Angiogenesis, as the process of new vessel formation from pre-existing vessels is dependent on a delicate equilibrium between endogenous angiogenic and antiangiogenic factors. However, under pathological conditions, this tight regulation becomes lost which can result in the formation of the different diseases such as cancer. Angiogenesis is a complex process that includes many gene products that are produced by different cells. Each of the processes influenced by specific genes that their expression can be regulated by hypoxi inducible factor-1 (HIF-1). Hypoxia, the imbalance between the oxygen in need and the oxygen available, usually occurs in tumors and ischemic cardiovascular diseases. In order to overcome this challenge, tumors regulate and control the expression of genes related to angiogenesis, cell cycle and metabolism using hypoxia-inducible factor 1 (HIF-1). HIF-1 was first recognized as a transcription factor involved in hypoxia-induced erythropoietin expression. As angiogenesis pathway molecules are being described, this factor has been characterized as a key transcription regulator for these molecules. In this review article, after discussing HIF-1 structure and characterization, the role of this important factor in angiogenesis and cancer as a pathological case and finally, the clinical applications has been evaluated. Articles related to the key words of hypoxia, HIF-1 and angiogenesis were searched from valid databases such as Springer Link, google scholar, Pubmed and Sciencedirect. Then, the articles related to the role of hypoxia and HIF-1 in activation of genes that are involved in angiogenesis and cancer were searched and selected for this study. Studies show that, HIF-1 activation of genes including vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), etc., induced angiogenesis in the tumor cells. Furthermore, the activation of genes such as insulin-like growth factor 2 (IGF2), transforming growth factor α (TGF-α) and MAPK and PI3K signaling pathway will also enable the survival and proliferation of tumor cells. HIF-1 by activating genes involved in angiogenesis and also activates signaling pathways associated with cell survival and proliferation plays an important role in the stability and growth of tumors. Therefore, better understanding of molecular mechanisms associated with this factor can be effective in the treatment of cancer.

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