فهرست مطالب

Basic and Clinical Cancer Research
Volume:13 Issue: 2, Spring 2021

  • تاریخ انتشار: 1401/01/07
  • تعداد عناوین: 8
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  • Ghazaleh Ganjipour, Masomeh Heshmati, Mehrdad Hashemi, Maliheh Entezari Pages 84-91
    Background

    Breast cancer is considered the second prevailed type of cancer among women. Circular RNAs are a group of non-coding RNAs that play a significant role in tumorigenesis and the progression of malignancies. This study aimed to determine the inhibitory concentration (IC50) of iron superoxide (Fe2O3) and nickel oxide (NiO) nanoparticles and coenzyme Q10 (Q10) antioxidant against 4T1 cell line and their single and combination treatment effect on hsa_circ_0001518 expression in healthy and breast tumor mice.

    Methods

    The 4T1 cell line was cultivated and treated with Fe2O3 (50, 100, 150, and 200 μg/mL) and NiO (10, 20, 30, and 40 μg/mL) nanoparticles, and Q10 antioxidant (20, 60, 80, and 100 μg/mL) for 48 hours. Cell viability was measured using the MTT assay. The expression of hsa_circ_0001518 after treatment with the half-maximal inhibitory concentration (IC50) of all single and combined antioxidant and NPs in healthy and breast tumor-bearing mice were evaluated by qRT-PCR.

    Results

    The IC50 of Fe2O3 and NiO nanoparticles and Q10 antioxidant after 48h was 92.42 μg/mL, 21.49 μg/mL, and 83.47 μg/mL, respectively. The qRT-PCR results showed that combined treatment with antioxidant and NPs caused a more significant downregulation in the expression of has_circ1518 in breast tumor-bearing mice than either agent alone. In addition, combined treatment with antioxidant and NPs caused a more significant downregulation in the expression of has_circ1518 in breast tumor-bearing mice than either agent alone.

    Conclusion

    This study suggests that the combined treatment of Fe2O3 and NiO nanoparticles with Q10 could be exploited as a potential source for developing novel drugs against breast cancer.

    Keywords: Breast Cancer, circRNA, Iron Superoxide Nanoparticles, NickelOxide Nanoparticles, Q10 antioxidant
  • Arash Abdolmaleki, Aida Karimian, Asadollah Asadi*, Hussein A. Ghanimi, Muhammad Akram Pages 92-104

    Cancer is a genetic illness that develops for a variety of reasons, including the activation of onco-genes, the failure of tumor suppressor genes, or mutagenesis induced by environmental stimuli. This article was produced using data from the journals PubMed, Nature, Science Direct, Springer, and Elsevier. Oncogenes are altered forms of normal proto-oncogenic genes that are important for cell proliferation, development, and regulation. The transformation of a gene to an oncogene is caused by translocation, chromosomal translocation, or gene mutation due to addition, deletion, duplication, or viral infection. To limit malignant cell development, these oncogens are targeted by medications or the RNAi system. Various molecular biology methods for cancer detection and treatment have been developed, including retroviral therapy, oncogene silencing, and alterations in tumor suppressor genes. Among all the techniques used, RNAi, zinc finger nucleases, and CRISPR have a greater chance of reaching a cancer-free planet.

    Keywords: Brain Tumor, Cancer, Molecular Biology, Oncogenes
  • Rahmatollah Moradzadeh*, Shahla Mirgaloybayat Pages 105-110
    Background

    Identifying the local foci and clusters of diseases can help reduce incidence and mortality by making necessary interventions. This study aimed to detect possible colorectal cancer incidence clusters using spatial analyses at point-level data at small census units in Arak, Iran, from 2009 to 2014.

    Methods

    In this ecologic study, recorded data on colorectal cancer in Arak were collected from the Arak Cancer Registry. All records were evaluated using various methods to detect and resolve probable error events or duplicated records. Then, SaTScan software was used to explore spatial clusters. The Discrete Poisson-based Probability Model was utilized to analyze the clusters.

    Results

    A total of 398 incident cases of colorectal cancer were identified. The mean age at diagnosis was 62.8 ± 14.6 years. Among colorectal cancer cases, 179 (45%) and 219 (55%) were females and males, respectively. Most cases were categorized with colon topography codes (n = 119, 66.5%). Three spatial clusters of colorectal cancer using individual geocodes were detected. The most high-risk cluster was located near the southern highway in Arak, a highway with transit routes for heavy and light vehicles (p=0.0004). The second significant high-risk cluster was a district located in the vast part of the center of Arak (p=0.003). The third high-risk cluster was an area in the suburb of Arak, between Farmahin-Arak Road and Northern highway (p=0.06).

    Conclusion

    This study identified three essential clusters for the high incidence of colorectal cancer in Arak. The data would be useful for further evaluation of the environmental and lifestyle factors. Furthermore, the obtained pattern might be related to confounding impacts of environmental and lifestyle factors.

    Keywords: Colorectal Neoplasms, Iran, Spatial Clusters
  • Sahar Rostami, Azin Nahvijou * Pages 111-118
    Background

    Gynecologic cancers (GCs) are among the leading causes of morbidity and mortality in females worldwide. Estimating the cancer burden is invaluable to set up priorities for research funding allocations, cancer control policies, and prevention strategies. The International Agency for Research on Cancer (IARC) has recently released the latest estimates on the prevalence, incidence, and mortality for 36 types of cancer and all cancer sites combined in 185 countries in 2020. We aimed to report GCs estimates in the I.R. Iran from 2012 to 2040 based on the GLOBOCAN 2020.

    Methods

    We obtained data on the incidence, mortality, and prevalence of GCs in the Iranian female population from the GLOBOCAN 2020 database presented by the IARC, compared the burden with the previous reports presented in 2012 and 2018, and provided the estimates for 2040. In addition, we compared the burden to that of the WHO Eastern Mediterranean Region (EMRO) and the world.

    Results

    The top 3 incident GCs were ovarian, uterine, and cervical cancer, respectively. In 2020, approximately 2,000 new cases of ovarian cancer (ASR: 4.4), 1,535 new patients with uterine cancer (ASR: 3.5), and 1,056 incident cervical cancer cases (ASR: 2.3) were diagnosed in the I.R. Iran. With 1,269 cancer deaths and an age-standardized mortality rate (ASMR) of 3.0, ovarian cancer is considered to be the leading cause of death from GCs, followed by cervical cancer (644 deaths; ASMR: 1.5) and uterine cancer (537 deaths; ASMR: 1.3). Among 157,930 prevalent female cases reported in the GLOBOCAN 2020 database, 13,663 cases were categorized as GC. With a 5-year prevalence of 5,539, ovarian cancer was the most prevalent type, while uterine cancer (with 4,904 prevalent cases) and cervical cancer (with 2,948 prevalent cases) were less prevalent types.

    Conclusion

    There has been a slight increase in the incidence of GCs in recent years after stable rates for a couple of decades. Therefore, primary and secondary prevention measures such as lifestyle modifications and screening programs must be prioritized.

    Keywords: Gynecologic Cancers, Uterine Cancer, Ovarian Cancer, CervicalCancer, Cancer Burden
  • Zahra Valizadeh, Masoomeh Beheshti, Fatemeh Ashrafi, Soyar Sari, Raheleh Kheirbakhsh, Hadiseh Mohammadpour, Samad Mohammadnejad, Ahad Mohammadnejad, Saeid Amanpour, Marveh Rahmati * Pages 119-126
    Background

    4T1 is a mice transplantable mammary carcinoma cell line with highly tumorigenic and invasive properties, making it a suitable preclinical oncology model for triple-negative breast cancer (TNBC). This pilot study aimed to create a model of clinical stages in TNBC mice and to evaluate the response to treatment with paclitaxel (PTX) and doxorubicin (DOX) based on antiangiogenic effects

    Methods

    Syngeneic tumors were developed in BALB/c female mice by 4T1 cell line. The mice were randomly distributed into three different groups, each containing four. A group of four was considered as healthy normal. When tumor growth reached 100- 200 mm3 , two groups received the maximum tolerated dose (MTD) of PTX and DOX, respectively. Normal saline was injected into the sham control group. The tumors and tissue margins were removed by surgery one week following chemotherapy. Angiogenesis genes and microvessel density (MVD) were analyzed by real-time PCR and immunohistochemistry, respectively. Response to treatment was also assessed by standard methods of H&E staining.

    Results

    TNBC tumors were confirmed by pathological staining. The volume of tumors and the angiogenesis gene expressions of VEGFR1, VEGFR2, and HIF1α decreased in treated tumors compared to control (p < 0.05). Response to treatment to PTX was more than DOX, and the MVD decreased in both PTX and DOX chemotherapy groups.

    Conclusion

    Although PTX is more effective than DOX in reducing angiogenesis genes, both have the potential for treatment in the 4T1 mouse model.

    Keywords: Angiogenesis, Doxorubicin, Paclitaxel, Response to treatment, Triple-Negative Breast Cancer, 4T1 Tumor
  • Reza Ghaletaki*, Ali Kazemian, Saeed Rezaei, Fatemeh Soleimanian, Negin Mohammadi, Mahdi Aghili, Nima Mousavi Darzikolaee, Ebrahim Esmati Pages 127-132
    Background and Objective

    During the COVID-19 epidemic, concerns about cancer patients undergoing radiotherapy have increased because of the numerous hospital visits, which may increase the risk of contracting COVID-19. We aimed to investigate the incidence of COVID-19 among patients visiting our radiation oncology department during the first and second peaks of the epidemic.

    Methods

    In this cross-sectional study, we included all patients who underwent radiotherapy from November 2019 to September 2020. We contacted the patients and asked if they had COVID-19 during this time and how they were diagnosed. Clinical signs and a positive PCR test were acceptable as COVID-19 diagnostic criteria. We also gathered cancer and treatment status data from the patients’ records in the ward medical library. This study was approved by the institutional review board and ethics committee (code: IR.TUMS.VCR.REC.1399.104).

    Results

    During the study period, 687 patients were admitted to our radiation oncology ward. The patients’ median age was 55 (IQR: 44-65), of whom 424 (61.7%) were females. Twenty-three (3.3%) patients developed COVID-19, 15 (65.2%) of whom were diagnosed with clinical symptoms and 8 (34.8%) with PCR. Twelve and 11 patients contracted COVID-19 in the first and second epidemic peaks, respectively. Even though no patients with skin cancer or sarcomas of the bone or soft tissue contracted COVID-19, the highest frequency of COVID-19 was seen among patients with intrathoracic or lung cancer with 38 times the odds of patients with head and neck cancer to develop COVID-19. Highly susceptible patients were those with hematologic and upper gastrointestinal (GI) and gynecologic cancers, respectively. We found a significant association between intrathoracic (mainly lung) cancers and infection with COVID-19 (P-value = 0.02).

    Conclusion

    Patients undergoing intrathoracic cancer radiotherapy are at a higher risk of developing COVID-19. We believe these patients should be prioritized in cancer patients’ screening, case-finding, or vaccination programs.

    Keywords: COVID-19, Neoplasms, Radiotherapy, Lung Neoplasms, Screening, Vaccination
  • Marveh Rahmati, Narges Sadat Ahmadmiri, MohammadAmin Moosavi Pages 133-142

    The unfolded protein response (UPR) is an evolutionarily conserved adaptive pathway, which is activated by the stress of the endoplasmic reticulum (ER). ER stress often occurs due to the high protein demand in cells and protein folding errors in several diseases, such as different cancers and autoimmune diseases. UPR is mediated by three primary arms called inositol-requiring enzyme-1α (IRE1α), protein kinase RNA-like endoplasmic reticulum kinase (PERK), and activating transcription factor 6α (ATF6α). Given that homeostasis in protein synthesis is frequently deregulated in cancers, UPR plays a critical role in controlling survival and cell death. In addition,, resistance to ap- optosis is mediated by the pro-survival mechanism of ER stress in cancer cells. Recent evidence highlighted the deregulation of UPR signaling in hematopoietic stem cells (HSCs) and leukemic cells, so that targeting UPR-driven pro-survival pathways may present new therapeutic benefits in leukemia. In this review article, we aim to provide an updated knowledge on the role of UPR as a novel therapeutic target in leukemia. We first define the different types of leukemia and their challenges with current treat- ments, and then explore the contribution of UPR to leukemia pathogenesis and treat- ment. Finally, UPR targeting strategies in pre-clinical and clinical trials of patients with leukemia will be presented.

    Keywords: Endoplasmic reticulum stress (ER), Leukemia, Targeted thera-py, Unfolded protein response (UPR)
  • Roghayeh Fekri, Arash Abdolmaleki, Asadollah Asadi, Mehdi Salehi, Aida Karimian, Leila Taghizadehmomen, Rehab K Raheem, Lia Karimian Pages 143-155

    Cancer treatment has traditionally been comprised of established treatments such as radiation, surgical excision, and chemotherapy, which can be used alone or in combination. Many therapeutic factors have been extracted from minerals, plants, and animals, the majority of them have been synthesized in the lab, making them a valuable source of innovation pharmacologically. Due to the in vitro cytotoxic effect of metal complexes, the interest in these compounds increases day by day in cancer treatment. The electronic nature of metals, modifications in ligands, and conformational changes in functional groups give rise to the discovery of drugs with different cytotoxic and pharmacokinetic properties. In recent decades, the number of persons receiving chemotherapy has increased considerably. Medicinal inorganic chemistry can take advantage of the unique properties of metal ions to generate new drugs. This has prompted chemists to use various approaches creating novel metal-based anticancer drugs with various mechanisms of action, which are significant in the pharmaceutical industry due to their potent anticancer properties. Schiff base ligands and transition metals are the most researched coordination chemicals. Their applications as anticancer medicines are becoming more significant. This research analyzes various publications linked to copper complexes based on Schiff base hydrazone ligand in cancer treatment, and this review will analyze publications on these compounds' anticancer qualities.

    Keywords: Anticancer, Copper (II) complexes, Hydrazone, Schiff base ligands