فهرست مطالب

  • Volume:13 Issue: 8, 2020
  • تاریخ انتشار: 1399/06/17
  • تعداد عناوین: 7
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  • Reyhane Sefidkar, Amir Kavousi *, Mahmoud Torabi, Seyyed Vahid Hosseini, Hojat Alaii Page 1
    Background

    Colorectal cancer (CRC) is one of the main causes of mortality and morbidity worldwide. Socio-economic status is one of the most important related factors with CRC.

    Objectives

    In this study, we used the human development index (HDI) as one of the common measures of socio-economic status to predict the incidence rate of CRC in the counties of Fars Province in Iran.

    Methods

    In this ecological study, we used the medical records of 108 patients with CRC from Fars province, who referred to Shahid Faghihi Hospital in Shiraz from January 2011 to March 2013. Since sample sizes were not efficient in all the counties, we used the log-normal model within small area estimation framework to have a reliable prediction for the incidence rate in each county. As using related auxiliary variables is necessary in small area models, we considered the HDI of counties as an auxiliary variable.

    Results

    The findings showed that there was a significant direct relationship between HDI and CRC incidence rate. Furthermore, the highest predicted rates were observed in the northern and eastern parts of the province.

    Conclusions

    In order to compensate the deficiency of sample size in some of the counties, we used a small area model to predict the CRC incidence rate. The highest incidence rates mostly occurred in the counties with the highest HDI. It is observed that the counties with higher incidence rates are closer to more industrial provinces and the counties with lower incidence rates are closer to less industrial provinces. So, it seems that development disparities strongly affected the incidence rates.

    Keywords: Incidence, Colorectal Neoplasms
  • Behnoosh Tahbazlahafi, Malihe Paknejad, Shiva Shahmohamadnejad, Alireza Mirzaei, Khodamorad Jamshidi, Ehsan Khalili * Page 2
    Background

    Osteosarcoma (OS) is the most common type of bone malignancy. Many studies have attempted to find the association between microRNAs and cancer-associated processes. Alterations in miRNA expression through genetic or epigenetic changes, impairment of transcription factors, and ectopic expression of miRNAs induce the development and progression of cancer. Although miR-135b has been thoroughly documented as an oncogene in the majority of studies, some controversies remain about the conflicting role of miR-135b as a tumor-suppressor.

    Objectives

    The present study aimed at investigating the oncogenic and/or tumor-suppressing role of miR-135b in human OS.

    Methods

    In this study, 21 OS tissue samples, along with 21 adjacent bone tissues (normal) as control specimens were collected to analyze the expression of miR-135b. The Saos2 cell-line was transiently transfected with the miR-135b mimic and inhibitor to assess its effect on two critical transcription factors, namely FOXO-1 and c-Myc. qRT-PCR was performed to quantify the expression of miR-135b in both OS tissues and the Saos2 cell-line. The MTT, cell migration, and cell invasion assays were used to characterize the miR-135b function. The western blot analysis was carried out to monitor the targets of miR-135b. Finally, the changes in cellular functions such as migration and invasion, following the transfection of miR-135b mimic and inhibitor, were verified.

    Results

    The results showed that in comparison with the adjacent normal bone tissues, the expression of miR-135b was higher in OS tissue samples, which inversely correlated with the expression rate of FOXO-1, whereas the expression of c-Myc had a direct relationship to miR-135b expression. Functionally, the miR-135b mimic led to an increase in cell proliferation, invasion, and migration of OS cancer cells.

    Conclusions

    MiR-135b induces the proliferation and invasion of OS cells by the degradation of FOXO-1 and upregulation of c-Myc.

    Keywords: Osteosarcoma, Cell Invasion, c-Myc, FOXO-1, miR-135b
  • Amirreza Famil Dardashti, Ali Hajigholami, Shirinsadat Badri, Afsaneh Yekdaneh, Azadeh Moghaddas, * Page 3
    Background

    Anorexia and cachexia are one of the major problems in patients suffering from advanced malignancies.

    Objectives

    This study aimed at evaluating the efficacy of herbal combination containing Fenugreek, Fennel, and Chicory supplementation to the high-dose megestrol for the treatment of cancer-induced cachexia and anorexia.

    Methods

    This quasi-experimental study was performed on 47 adult patients with advanced malignancy; they experienced anorexia and weight loss over the 2 past months and referred to a university-affiliated hospital (Omid) in Isfahan, Iran. Patients who had met the inclusion criteria were assigned to take either herbal combination or placebo tablets in addition to megestrol (160 mg daily) for a 2-month follow-up. All patients’ demographic information, weight changes, anthropometric indices, as well as the quality of life criteria were recorded at the baseline and after the duration of follow-up.

    Results

    Patients in the herbal combination group experienced a mean weight gain of 1.5 kg, while patients in the placebo group had an average weight loss of 0.6 kg. Anthropometric indices including triceps skinfold thickness, mid-arm muscle circumference index, and grip strength were significantly improved in the herbal combination group. The other evaluated criteria such as quality of life, functional assessment of anorexia/cachexia therapy (FAACT), and some factors of Anderson criteria were significantly improved in the herbal combination group than the placebo group.

    Conclusions

    Given the ameliorated results of the herbal combination supplementation in terms of weight gain and appetite improvement, as well as physical and quality of life enhancement, it seems that the herbal combination can be used as an adjunctive treatment for the management of patients suffering from cancer-induced cachexia and anorexia.

    Keywords: Cancer, Chicory, Anorexia, Fenugreek, Fennel, Cachexia, Herbal Combination
  • Zahra Zolghadr, Masoud Salehi, Afsaneh Dehnad, Farid Zayeri * Page 4
    Background

    Female breast cancer is known as one of the top five cancers in terms of mortality. Regarding contradictory reports about the mortality trend of this cancer and its association with the socio-economic status of the world countries, we aimed at assessing the global trend of female breast cancer mortality rate and investigate the relationship between its mortality rate and development status.

    Methods

    The breast cancer Age Standardized Mortality Rate (ASMR) per 100,000 and Human Development Index (HDI) for 179 world countries were extracted, respectively from the Global Burden of Disease (GBD) 2017 study and the United Nations Development Programme (UNDP) database, for the period 1990 to 2017. The marginal modeling methodology was employed to analyze the global trend of ASMR and examine the relationship between ASMR and HDI.

    Results

    The results showed a slightly constant curve for the global trend of breast cancer ASMR from 1990 to 2017 (around 17 per 100,000). Moreover, it was indicated that the ASMR is strongly related to development status. While countries with higher levels of HDI have experienced a declining trend of breast cancer mortality rate, countries with lower HDI levels experienced an ascending trend at this period.

    Conclusions

    In general, the findings showed that mortality due to breast cancer is still a major health problem in total world countries. Hence, more efforts should be made to screen the patients in the early stages of the disease and promote the level of care, especially in countries with lower levels of economic development.

    Keywords: Mortality, Breast Neoplasm
  • Solmaz Hashemi, Seyedmohammadreza Javadi, Mohammad Esmaeil Akbari *, HamidReza Mirzaei, Seied Rabi Mahdavi Page 5
    Background

    Radiotherapy plays an essential role in breast cancer treatment following breast conserving surgery even in good-risk patients with ductal carcinoma in situ (DCIS) histology. It can be delivered by many techniques, among which is intraoperative radiotherapy (IORT). In recent years, intraoperative radiation therapy has had the same outcome compared with EBRT.

    Objectives

    We studied whether whole breast radiotherapy (WBRT) could safely be replaced by IORT and its ability to control local recurrence like EBRT in pure DCIS.

    Methods

    We assigned 138 patients into the external beam radiotherapy (EBRT), radical, and boost groups. The patients were treated during the last 6 years in the Cancer Research Center of Shahid Beheshti University of Medical Sciences. A total of 57 patients received EBRT, 45 patients received the radical dose of radiotherapy by IORT (36 patients received intraoperative electron radiotherapy [IOeRT] and 9 patients received intraoperative X-ray radiotherapy [IOxRT]) according to the IRIORT consensus protocol, and 36 patients received the boost dose of radiotherapy by IORT (15 patients received IOeRT and 21 patients received IOxRT). The IORT and EBRT groups were compared. The primary endpoint was local recurrence and death and the secondary endpoint was the role of variables in local recurrence.

    Results

    With the mean follow-up of 37 months for the IORT group and 40.1 months for the EBRT group, local recurrence occurred in 8.8% (5 patients), 13.9% (5 patients), and 2.2% (1 patient) of the patients in the EBRT, boost, and radical groups, respectively. Concerning the local recurrence, no significant difference was observed between the radical and EBRT groups (P = 0.058) and between the boost and EBRT groups (P = 0.12). Hazard ratios (HRs) of grade, hormone receptor (HR), tumor size, and age in disease-free survival were evaluated and none of these variables had a significant role in local recurrence.

    Conclusions

    IORT is a good alternative for WBRT in DCIS patients because of its non-inferiority results in comparison with EBRT. Being careful about age, tumor size, biological markers, and margin status is of high importance when using IORT for DCIS.

    Keywords: IORT, DCIS, Breast Conserving Surgery
  • Reza Negarandeh, Zahra Yazdani, *, Rebecca Lehto, Marzieh Lashkari Page 6
    Background

    There is increasing awareness that patients with cancer desire information as well as strategies to support their capacity to actively participate in informed decision-making. This study will evaluate outcomes of using a question prompt list (QPL) on shared decision making (SDM), decision-making self-efficacy, and preferences for participation among Iranian women with breast cancer, who are referred to a Tehran Comprehensive Cancer Center.

    Methods

    This research will utilize a randomized controlled trial. The research population is patients with breast cancer, who are referred to the Oncology Radiotherapy Unit, Imam Khomeini Hospital, Tehran following tumor resection. After completing baseline surveys (demographics and health survey, decision self-efficacy scale, and control preferences scale), participants will be randomized into either a control or a treatment group based on block design. The treatment group will receive routine care along with the QPL that provides information on decision-making relative to treatment options (chemotherapy, radiotherapy, or both treatments) following meeting their oncologist. They will be trained to use the QPL which they will use to ask questions about their treatment choices when meeting with their physician or through computer-mediated modalities such as WhatsApp or other social messengers. These patients will have the opportunity to think about the treatment options and will be referred for medical treatment following their decision. The control group will receive routine care (physician discussion and receipt of treatment information). Following decision-making regarding treatment, the questionnaires will be administered (9-item SDM questionnaire, decision self-efficacy scale, and control preferences scale). Data will be analyzed using SPSS 16.

    Discussion

    The current study will provide experimental evidence for the preliminary efficacy or lack of an intervention that has the potential to improve shared decision-making outcomes, a better understanding of personal preferences related to decision-making and self-efficacy in medical decision-making for Iranian patients with breast cancer.
    Keywords

    Keywords: Cancer, Iran, Participation, Self-Efficacy, Preferences, Shared-Decision Making, Question Prompt List
  • Makhdoom Sarwar *, Peter Sykes, John J Evans Page 7

    Dear Editor, Ovarian cancers, often diagnosed with stage III/IV disease, recur frequently and eventually become resistant to standard chemotherapy. Despite an improvement in our understanding of ovarian cancer causes, survival rates have remained consistently low due to the lack of early symptoms. The 5-year survival rate in patients with an advanced stage (FIGO stage III and IV) is less than 30% as therapies become ineffective in treating metastatic ovarian cancer (1). Most epithelial ovarian cancers are of high-grade serous (HGS-OV) histology. Little is known about the pathogenesis of HGS-OV cancer because of the late-stage presentation in most cases, due to its rapid dissemination. However, there is now extensive evidence that most HGS-OV cancers arise from serous tubal intraepithelial carcinoma (STIC) in the distal region (fimbriae) of fallopian tube epithelium (2, 3). Other ovarian cancer subtypes are also thought to arise from non-ovarian tissue sources such as endometrioid and clear cell derived from endometriosis, whereas mucinous is often a metastasis from a gastrointestinal source (4, 5). This preliminary travel may imply that migration is a very early process in the tumorigenesis even before the onset of the primary tumor and thus indicative of adhesion mechanisms being involved in the disease in a very early stage. It is intriguing to wonder how much oncogenic potential tumor initiating cells (TICs) carry before adhering and colonizing in the ovarian tissue. Thus, ovarian tissue provides a breeding ground for these incoming highly invasive tumor cells, which is indicative of ovarian tissue being rich in resources required to hold and nurture the tumorigenic process. Disease progression is followed by another invasion event but this time in the opposite direction, from the ovary to distant organs. Ovarian cancer typically metastasizes either directly to the adjacent organs or through the dissemination of exfoliated tumor cells into the peritoneum, in contrast to most of the other cancer types where lymph nodes are usually involved. Additionally, recurrent or late disease tumor cell clusters floating in the ascitic fluid show distinct expression of adhesion complex-related proteins and are often chemoresistant (6). All these observations suggest that adhesion-related molecules (ARMs) may be assigned far more therapeutic importance than they currently enjoy. Non-receptor tyrosine kinases, such as focal adhesion kinase (FAK) and proto-oncogene tyrosine-protein kinase Src (Src) are the key molecules of the focal adhesion system, which is a conduit of outside-to-inside signaling. The upregulation of FAK and Src have been reported in ovarian cancer. In particular, FAK (7) and Src (8) activity are much higher in advanced disease and are associated with poor survival rates. Notably, FAK and Src mutually activate each other. This pair of tyrosine kinases regulate intracellular signaling mechanisms associated with chemoresistance in ovarian cancer such as mitogen-activated protein kinase (MAPK) and PI3K/AKT (9). Ovarian cancer is a heterogeneous disease with several distinct malignant populations and often have stem cell-like cells within the tumor core or distant. A huge array of reports indicated that these immortal cancer stem cells (CSCs) are capable of self-renewal, pluripotency, and responsible for the recurrence and the resistance to clinical interventions. Accumulating evidence suggests that FAK/Src signaling also regulates stemness via several mechanisms and the inhibition of which reduce stemness in cancer cells via interacting stem cell markers such as CD133 (10). A phase II trial of dasatinib (Src inhibitor) as a monotherapy showed minimal therapeutic value (11). However, Src inhibitors in combination with microtubule stabilizers or platinum-based drugs block angiogenesis, invoke caspase-9 dependent activation of the intrinsic pathway, and downregulate cell proliferation markers and therefore are likely to induce a significant increase in drug sensitivity in ovarian cancers (12). As a single agent treatment, FAK inhibition also demonstrated a reduction in angiogenesis and an increase in paclitaxel sensitivity (7). Even though these and several other studies indicated that regulating adhesion-associated tyrosine kinases (AATKs) improve drug sensitivity in ovarian cancer, these are not yet adequately included in larger clinical trials. Bevacizumab, a non-receptor tyrosine kinase inhibitor, is approved for the treatment of epithelial ovarian cancers and may reduce angiogenesis and tumor burden. However, it is unclear whether anti-angiogenic therapy reduces the distant metastasis due to the unorthodox dissemination of ovarian cancer. In 2019, out of $168 million of NIH funding for ovarian cancer, very little was funded towards the multi-targeting approach-based projects, and AATKs were barely seen. Worldwide, a significant number of multi-targeted studies continually explored MEK (Mitogen-activated protein kinase kinase), PI3K, mTOR HER2, and poly ADP ribose polymerase (PARP) inhibitors and some cell cycle and immune checkpoint inhibitors in various combinations (13). However, none of the multi-targeted approaches yielded significantly durable progression free outcomes to date. It is beginning to appear that the onset of cancer is a communal effort of assorted components, hence, treatment approach that can target the systemic corruption of including intra- and extra-cellular factors may require to end the oncogenic disarray in the systemic homeostasis, especially in the case of ovarian cancer. The FAK/Src pair not only relays extracellular cues but also interacts with a number of pathways associated with the chemo-resistant disease, including PI3K/AKT, MAPK, and JAK/STAT signaling (Figure 1). Targeting ARMs will potentially broaden the horizon of combined treatment as it may not only override the environmental oncogenicity but may also normalize the aberrant intracellular signaling. It has been shown that interrupting aberrant ECM-to-cell signals mediated by integrins may normalize cell behavior and reverse tumor development (14). In addition, it was also suggested that the early development of ovarian cancer is dependent on potential tumor forming cells being bound to the sites in ovarian tissue with permissive, as distinct from tumor-inhibiting, characteristics (15). The commensurate inclusion of ARMs as a strategic component of a multi-targeted approach in larger clinical trials may therefore be warranted in ovarian cancer translation research. Such an approach will aim to develop clinical drugs of improved efficacy with the durable outcome by overcoming ovarian cancer cells’ resistance, a major challenge in the clinical management of ovarian cancer.

    Keywords: Cancer, Metastasis, Molecular Targeted Therapy