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Background The objective of this study was to compare the efficacy and side effects of a single dose (Pegfilgrastim or PDL) or repeated six daily injections (Filgrastim or PDG) during chemotherapy courses in breast cancer patients in a non-inferiority clinical trial. Methods In this randomized clinical trial, 80 patients were recruited and allocated randomly to two equal arms. In one group, a single subcutaneous dose of PDL was injected the day after receiving the chemotherapy regimen in each cycle. The second arm received a subcutaneous injection of PDG for six consecutive days in each cycle of treatment. The side effects of GCF treatment and its effect on blood parameters were compared in each cycle and during eight cycles of chemotherapy. Results Hematologic parameters showed no significant differences in any of the treatment courses between the two study groups. The comparison of WBC ( p  = 0.527), Hgb ( p  = 0.075), Platelet ( p  = 0.819), Neutrophil ( p  = 0.575), Lymphocyte ( p  = 705) and ANC ( p  = 0.675) changes during the eight courses of treatment also revealed no statistically significant difference between the two study groups. Side effects including headache, injection site reaction and muscle pain had a lower frequency in patients receiving PDL drugs. Conclusion It seems that PDL is non-inferior in efficacy and also less toxic than PDG. Since PDL can be administered in a single dose and is also less costly, it can be regarded as a cost-effective drug for the treatment of chemotherapy-induced neutropenia. Trial registration IRCT20190504043465N1 , May 2019.

Along with evolution, a considerable number of signaling cascades have evolved within cells to meet their multifaceted needs. Among transmitting molecules, phosphoinositide 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR) have teamed up to build a signaling axis that effectively regulates various cellular processes including cell proliferation and migration. Given the extensive output of the PI3K/Akt/mTOR signaling axis, its aberrancy could subsequently lead to the formation of a wide range of human cancers spanning from hematologic malignancies to different types of solid tumors. Despite the high frequency of the PI3K pathway over-activation in most malignancies, mutations in the DNA sequence are not equally common. Such incompatibility sheds light on the possible effects of post-translational modification mechanisms that may take control of this pathway, some of the most important ones of which are through microRNAs (miRNAs or miRs). The present review is designed to take off the veil from the regulatory role of these small non-coding RNAs on the PI3K/Akt/mTOR signaling axis in carcinogenesis.

Background Easy access to palliative care is one of the basic needs of cancer patients, and this can be achieved by providing such services at the community level. One approach to provide community-based palliative care is to integrate it with primary health care (PHC). Considering the antiquity and extension of the PHC system in Iran and the importance of being aware of stakeholders’ views in order to integrate a palliative care provision model into a country’s health care system, we aimed to explain health care providers’ perception of the integration of palliative care with PHC. Methods The present qualitative research was conducted using the conventional content analysis method in Iran from October 2016 to July 2020. The participants of the study included the stakeholders involved in providing palliative care to cancer patients, as well as PHC system experts. The participants were selected purposefully using the snowball sampling method. Data were collected through holding 21 semi-structured interviews and one focused group session and analyzed based on the method proposed by Lundman and Graneheim. Results Qualitative data analysis revealed three main categories and ten subcategories. The main categories included the health system’s structure as an opportunity (with the subcategories of employing the network system for providing health services, establishment of a referral system, and establishment of the family physician program and manpower diversity), requirements (with the subcategories of the position of home care centers and their relationship with PHC, opioid use management, equipment management, financial support, and legal issues), and outcomes (with the subcategories of facilitated access to services and good death). Conclusion Iran’s health system possesses adequate infrastructure for providing palliative care to cancer patients within the context of PHC. Beside available opportunities, there are also problems that need to be resolved so that families can meet their patients’ care needs and provide them with an easy death by having access to home-based palliative care.

Background and Aims Gastrointestinal neuroendocrine neoplasms (g‐NENs) represent a heterogeneous group of tumors with variable prognoses. Inflammation‐based markers, such as the neutrophil‐to‐lymphocyte ratio (NLR) and platelet‐to‐lymphocyte ratio (PLR), have emerged as potential prognostic indicators in various malignancies. This study aimed to evaluate the prognostic significance of NLR and PLR in g‐NENs and their associations with histopathological features and survival outcomes. Methods A retrospective, cross‐sectional study was conducted on 80 patients with histologically confirmed g‐NENs from April 2017 to March 2019. Baseline NLR and PLR were calculated, and their relationships with tumor grade, Ki‐67 proliferation index, metastatic status, and survival outcomes were analyzed. Cox regression and logistic regression models were used to determine independent prognostic factors. Results The hazard of death was approximately one‐third in the low NLR group after adjusting for metastasis and tumor grade (HR = 0.33, 95% CI: 0.14–0.80, p < 0.05). Elevated PLR was associated with poor outcomes; however, the difference between the high and low PLR groups was not statistically significant. Higher tumor grades and elevated Ki‐67 indices correlated with worse survival and increased metastatic potential (p < 0.001). No significant associations were observed for CRP or ESR levels with survival. Conclusion Our findings suggest that NLR may serve as an independent and accessible prognostic marker in g‐NENs, potentially offering a cost‐effective tool to support clinical decision‐making. The combined assessment of inflammatory biomarkers and histopathological parameters could improve prognostic accuracy and help guide personalized management strategies in patients with g‐NENs. Nevertheless, these observations should be interpreted with caution due to the retrospective, single‐center design and limited sample size. Future large‐scale, prospective studies are warranted to confirm and expand upon these results.

Background In the new era of tailored cancer treatment strategies, finding a molecule to regulate a wide range of intracellular functions is valuable. The unique property of nuclear receptor peroxisome proliferator‐activated receptor‐γ (PPARγ; PPARG) in transmitting the anti‐survival signals of the chemotherapeutic drugs has fired the enthusiasm into the application of this receptor in cancer treatment. Objectives We aimed to investigate the expression of PPARγ and one of its downstream targets PTEN in non‐M3 acute myeloid leukemia (AML) patients. We also investigated the therapeutic value of PPARγ stimulation using pioglitazone in the AML‐derived U937 cell line. Methods The blood samples from 30 patients diagnosed with non‐M3 AML as well as 10 healthy individuals were collected and the mRNA expression levels of PPARγ and PTEN were evaluated. Additionally, we used trypan blue assay, MTT assay, and flow cytometry analysis to evaluate the anti‐leukemic effects of pioglitazone on U937 cells. Results While PTEN was significantly downregulated in AML patients as compared to the control group, the expression of PPARγ was increased in the patients’ group. The expression level of PPARγ was also negatively correlated with PTEN; however, it was not statistically significant. Besides, PPARγ stimulation using pioglitazone reduced survival and proliferative capacity of U937 cells through inducing apoptosis and suppression of cell transition from the G1 phase of the cell cycle. Conclusion The results of the present study shed more light on the importance of PPARγ and its stimulation in the therapeutic strategies of AML. The unique property of nuclear receptor peroxisome proliferator‐activated receptor‐γ (PPARγ) in transmitting the anti‐survival signals of the chemotherapeutic drugs has fired the enthusiasm into the application of this receptor in cancer treatment. We found that the expression of PPARγ was increased in non‐M3 AML patients and activation of this receptor using pioglitazone reduced AML cell survival; shedding light on the importance of PPARγ and its ligands in the therapeutic strategies of AML.

Background Currently, the main goal of cancer research is to increase longevity of patients suffering malignant cancers. The promising results of BCc1 in vitro and vivo experiments made us look into the effect of BCc1 nanomedicine on patients with cancer in a clinical trial. Methods The present investigation was a randomized, double-blind, placebo-controlled, parallel, and multicenter study in which 123 patients (30-to-85-year-old men and women) with metastatic and non-metastatic gastric cancer, in two separate groups of BCc1 nanomedicine or placebo, were selected using a permuted block randomization method. For metastatic and non-metastatic patients, a daily dose of 3000 and 1500 mg was prescribed, respectively. Overall survival (OS) as the primary endpoint and quality of life (measured using QLQ-STO22) and adverse effects as the secondary endpoints were studied. Results In metastatic patients, the median OS was significantly higher in BCc1 nanomedicine (174 days [95% confidence interval (CI) 82.37–265.62]) than in placebo (62 days [95% CI 0–153.42]); hazard ratio (HR): 0.5 [95% CI 0.25–0.98; p = 0.046]. In non-metastatic patients, the median OS was significantly higher in BCc1 nanomedicine (529 days [95% CI 393.245–664.75]) than in placebo (345 days [95% CI 134.85–555.14]); HR: 0.324 [95% CI 0.97–1.07; p = 0.066]. The QLQ-STO22 assessment showed a mean difference improvement of 3.25 and 2.29 ( p value > 0.05) in BCc1 nanomedicine and a mean difference deterioration of − 4.42 and − 3 (p-value < 0.05) in placebo with metastatic and non-metastatic patients, respectively. No adverse effects were observed. Conclusion The findings of this trial has provided evidence for the potential capacity of BCc1 nanomedicine for treatment of cancer. Trial registration IRCTID, IRCT2017101935423N1. Registered on 19 October 2017, http://www.irct.ir/ IRCT2017101935423N1

COVID-19 was introduced by the World Health Organization (WHO) as a global pandemic. The disease manifestations ranges from a mild common cold to severe disease and death. It has a higher mortality rate in people with a history of comorbidities, including cardiovascular disease (CVD) and can also contribute to cardiac injury. This study was conducted to evaluate the relationship between troponin levels as a cardiac marker and adverse outcomes in this disease. The study sample included 438 patients hospitalized with COVID-19; however, the troponin data of 6 patients were not available. The need to be admitted to the intensive care unit (ICU), and death were considered the adverse outcome in patients with COVID-19. Troponin levels were checked in all patients on day 1 and day 3 of hospitalization. Multiple logistic regression analysis was performed to determine whether there was an independent association between the adverse outcomes and troponin enzyme in hospitalized patients with COVID-19. The mean age of patients was 61.29 ± 15.84 years. Among the 432 patients tested on day 1 of hospitalization, 24 patients (5.6%) tested positive (Troponin 1), and among the 303 patients tested on day 3, 13 patients (4.3%) tested positive (Troponin 2). Based on our results, Troponin 1 showed an independent association with both death (3.008 [95%CI = 1.091-8.290]; P = 0.033) and need for ICU admission (8.499 [95%CI = 3.316-21.788]; P < 0.001) in multiple logistic regression analysis. Moreover, the status of Troponin 2 had an independent significant association with both death (4.159 [95%CI = 1.156-14.961]; P = 0.029) and ICU admission (7.796 [95%CI = 1.954-31.097]; P = 0.004). Troponin showed a significant association with adverse outcomes in people who were hospitalized with COVID-19. The periodical assessment of this enzyme from the time of hospitalization may improve the clinical decision making of clinicians.

The objective of this study was to compare the efficacy and side effects of a single dose (Pegfilgrastim or PDL) or repeated six daily injections (Filgrastim or PDG) during chemotherapy courses in breast cancer patients in a non-inferiority clinical trial. In this randomized clinical trial, 80 patients were recruited and allocated randomly to two equal arms. In one group, a single subcutaneous dose of PDL was injected the day after receiving the chemotherapy regimen in each cycle. The second arm received a subcutaneous injection of PDG for six consecutive days in each cycle of treatment. The side effects of GCF treatment and its effect on blood parameters were compared in each cycle and during eight cycles of chemotherapy. Hematologic parameters showed no significant differences in any of the treatment courses between the two study groups. The comparison of WBC (p = 0.527), Hgb (p = 0.075), Platelet (p = 0.819), Neutrophil (p = 0.575), Lymphocyte (p = 705) and ANC (p = 0.675) changes during the eight courses of treatment also revealed no statistically significant difference between the two study groups. Side effects including headache, injection site reaction and muscle pain had a lower frequency in patients receiving PDL drugs. It seems that PDL is non-inferior in efficacy and also less toxic than PDG. Since PDL can be administered in a single dose and is also less costly, it can be regarded as a cost-effective drug for the treatment of chemotherapy-induced neutropenia.

Tamoxifen is one of the most used drugs for breast cancer. This study aimed to investigate the effect of the Tamoxifen mechanism on the epithelial-mesenchymal transition (EMT) pathway among breast cancer patients due to its resistance to breast cancer cells. We selected the appropriate datasets from the GEO database using continuous and integrated bioinformatics analysis. We examined the signaling pathways, gene ontology, and protein association of genes after classifying the gene expression profile. Finally, we confirmed the candidate genes using the GEPIA database. Two groups were defined for gene expression profiles. The first group in which the expression profile of genes increased after Tamoxifen was evaluated using the expression profile of genes that decreased in the EMT pathway. The second group was the opposite of the first group. 253 genes in the first group and 302 genes in the second group were shared. The genes in the first group were involved in various pathways of cell death, focal adhesion, and cellular aging. The second group was more involved in different phases of the cell cycle. Finally, MYLK, SOCS3, and STAT5B proteins from the first group and BIRC5, PLK1, and RAPGAP1 proteins from the second group were selected as candidate proteins in connection with the effect of Tamoxifen on the EMT pathway. We evaluated Tamoxifen's effect on the EMT pathway more accurately. However, for a closer look at Tamoxifen, more studies need to be done on target genes and proteins to clarify their role.

Coastal areas are expected to be at a higher risk of flooding when climate change-induced sea-level rise (SLR) is combined with episodic rises in sea level. Flood susceptibility mapping (FSM), mostly based on statistical and machine learning methods, has been widely employed to mitigate flood risk; however, they neglect exposure and vulnerability assessment as the key components of flood risk. Flood risk assessment is often conducted by quantitative methods (e.g., probabilistic). Such assessment uses analytical and empirical techniques to construct the physical vulnerability curves of elements at risk, but the role of people’s capacity, depending on social vulnerability, remains limited. To address this gap, this study developed a semiquantitative method, based on the spatial multi-criteria decision analysis (SMCDA). The model combines two representative concentration pathway (RCP) scenarios: RCP 2.6 and RCP 8.5, and factors triggering coastal flooding in Bandar Abbas, Iran. It also employs an analytical hierarchy process (AHP) model to weight indicators of hazard, exposure, and social vulnerability components. Under the most extreme flooding scenario, 14.8% of flooded areas were identified as high and very high risk, mostly located in eastern, western, and partly in the middle of the City. The results of this study can be employed by decision-makers to apply appropriate risk reduction strategies in high-risk flooding zones.