Tumorigenic and tumoricidal properties of exosomes in cancers; a forward look.

In recent decades, emerging data have highlighted the critical role of extracellular vesicles (EVs), especially (exosomes) Exos, in the progression and development of several cancer types. These nano-sized vesicles are released by different cell lineages within the cancer niche and maintain a suitable platform for the interchange of various signaling molecules in a paracrine manner. Based on several studies, Exos can transfer oncogenic factors to other cells, and alter the activity of immune cells, and tumor microenvironment, leading to the expansion of tumor cells and metastasis to the remote sites. It has been indicated that the cell-to-cell crosstalk is so complicated and a wide array of factors are involved in this process. How and by which mechanisms Exos can regulate the behavior of tumor cells and non-cancer cells is at the center of debate. Here, we scrutinize the molecular mechanisms involved in the oncogenic behavior of Exos released by different cell lineages of tumor parenchyma. Besides, tumoricidal properties of Exos from various stem cell (SC) types are discussed in detail.

Cross-Cultural Adaptation and Psychometric Validation of the Interview Satisfaction Questionnaire (ISQ) to Assess Unmet Health Communication Needs of Iranian Breast Cancer Patients.

Autonomous and patient-centered health communication (PCHC) between a healthcare provider (HCP) and a client (HCC) is a critical fundament for successful healthcare outcomes. A standard and validated data collection tool for studying the satisfaction of Iranian breast cancer patients (BCPs) with various aspects of their health communication with HCPs does not exist. The current study assessed the application, feasibility, and cultural appropriateness of the Persian-translated version of the interview satisfaction questionnaire (ISQ) in the Iranian context. A standard translation/back-translation procedure was used to prepare a preliminary Persian version of the ISQ (ISQ-P) which was then evaluated for content and face validity by a panel of experts. The study data were collected from 200 breast cancer patients and used to estimate the internal consistency measure of Cronbach's alpha and intra-class correlation coefficient. Confirmatory factor analysis (CFA) was performed to verify the compatibility of the instrument's identified dimensions with the original ISQ's factor structure. The calculated content validity index (CVI = 0.89), content validity ratio (CVR = 0.49), and Cronbach's alpha coefficient (0.79) indicated the appropriateness of the ISQ-P for its intended purpose. The CFA's outputs (root mean square error of approximation (RMSEA) = 0.09, comparative fit index (CFI) = 0.954, Tucker-Lewis index (TLI) = 0.931, standardized root mean square residual (SRMR) = 0.04) affirmed the fitness of the study data to the original 4-factor conceptual model. The study findings supported the suitability of ISQ-P for assessing health communication episodes by Persian-speaking BCPs. However, due to cultural variation, cross-border diversity of health systems, and organizational circumstances, further validity and reliability appraisal of the ISQ-P in distinct sub-samples is recommended.

Comparison of global decolonization efficacy with mupirocin nasal drop and chlorhexidine mouthwash in acute leukemia patients: randomized clinical trial.

PURPOSE: Neutropenic fever remains a major complication in acute leukemia. Decolonization is assumed as a promising intervention for eradicating causative agents of infection. METHODS: In this randomized clinical trial, 96 patients with acute leukemia were assigned randomly to mupirocin nasal drop 2% (n = 32), chlorhexidine mouthwash 0.2% (n = 33), and control group (n = 31). In control group, patients did not receive any medication for decolonization. All patients received treatment for 5 days (2 days prior to chemotherapy until 3 days after chemotherapy). Pharynx and nasal swabs were taken prior to the intervention and at the end of decolonization period in all groups. Antibiotic susceptibility testing was performed by the disc diffusion method in order to identify bacterial isolates. RESULTS: Bacterial recovery of both nasal and pharynx swabs was observed after global decolonization with mupirocin nasal drop. Decolonization with mupirocin significantly eradicated Coagulase-negative staphylococci (CONS) in both nasal and pharynx swabs (p-value = 0.000). Moreover, mupirocin decreased Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) species. Chlorhexidine mouthwash significantly eradicated CONS in pharynx swabs (p-value = 0.000). In addition, both decolonization strategies decreased both antibiotic use and frequency of fever in leukemic patients. CONCLUSION: Global decolonization with mupirocin nasal drop not only eradicates both nasal and pharynx microorganisms, but also reduces antibiotic requirement and frequency of fever in patients with acute leukemia. The protocol of the present study was approved on December 2016 (registry number: IRCT20160310026998N6).

Oxidative stress regulation and related metabolic pathways in epithelial-mesenchymal transition of breast cancer stem cells.

Epithelial-mesenchymal transition (EMT) is a cell remodeling process in which epithelial cells undergo a reversible phenotype switch via the loss of adhesion capacity and acquisition of mesenchymal characteristics. In other words, EMT activation can increase invasiveness and metastatic properties, and prevent the sensitivity of tumor cells to chemotherapeutics, as mesenchymal cells have a higher resistance to chemotherapy and immunotherapy. EMT is orchestrated by a complex and multifactorial network, often linked to episodic, transient, or partial events. A variety of factors have been implicated in EMT development. Based on this concept, multiple metabolic pathways and master transcription factors, such as Snail, Twist, and ZEB, can drive the EMT. Emerging evidence suggests that oxidative stress plays a significant role in EMT induction. One emerging theory is that reducing mitochondrial-derived reactive oxygen species production may contribute to EMT development. This review describes how metabolic pathways and transcription factors are linked to EMT induction and addresses the involvement of signaling pathways.

Arteriovenous thrombosis, a complication of induction therapy with all-trans retinoic acid for acute promyelocytic leukemia: A case report.

We report a case of arterial and venous thrombosis during induction therapy. This case emphasizes considering some degree of caution for thrombotic events in APL patients which was represented in our case as abdominal pain. Rapid initiation of anticoagulation and preventive measures is suggested for better management of the condition.

The effectiveness of omega-3 fatty acids on health outcomes in women with breast cancer: A systematic review.

This study aimed to systematically evaluate the impact of omega-3 fatty acids on the health outcomes of women with breast cancer in electronic databases (PubMed, Scopus, ProQuest, Web of Science, and Cochrane Library) for interventional studies. The risk of bias and the quality of the included articles were assessed by Cochrane Collaboration Handbook guidance. The statistical analyses were not conducted because of the heterogeneity of the included studies. Of 3676 identified articles, 11 articles were included in this study. The majority of the included studies were not of high quality. Median progression time and overall survival significantly improved. Additionally, surgical site healing complications and infection rates decreased. There was a significant decrease in perceived stress, sleep disturbance, depression, pain, joint stiffness, and fatigue throughout the intervention. Moreover, omega-3 fatty acids consumption significantly increased the total serum omega-3, EPA, and DHA, and decreased the omega-6: omega-3 ratio, total leukocytes, lymphocytes, leptin, and CRP, accordingly. Mild gastrointestinal symptoms were reported in only two studies without clinically relevant adverse events. Omega-3 fatty acids may cause improvement in physical, mental, and some inflammatory and metabolic indices during treatment or posttreatment course of breast cancer patients. Due to the possibility of free radical formation, omega-3 FAs supplementation and consumption must be done very carefully.

Enhancing Cancer Pain Self-Management: A Holistic Supporting Model.

Introduction: Pain self-management is crucial in reducing pain intensity and improving the quality of life for cancer patients. By acquiring self-management skills, patients can actively participate in managing their pain. Objective: The objective of this study was to develop a grounded theory-based model to assist cancer patients in enhancing their pain self-management. Methods: This qualitative research was conducted in two stages from 2019 to 2021. The initial phase utilized a grounded theory approach to explore the process of pain self-management in cancer patients. Following Corbin and Strauss' analytical method, a grounded theory of pain management in cancer patients was identified. Subsequently, Walker and Avant's theory synthesis strategy was employed to construct a practical model that provides support for patients in managing their pain. Results: Within the conceptual framework, this study developed the "Holistic Supporting from Pain Self-Management" model. This supportive model consists of three main components: (1) enhancing pain self-management skills in cancer patients and their families, (2) empowering physicians and nurses in pain management for cancer patients, and (3) improving the organizational structure for pain management in cancer patients. Conclusion: The Holistic Supporting from Pain Self-Management model emphasizes the importance of addressing all dimensions of cancer pain, including physical, functional, psychosocial, cultural, and spiritual aspects, to effectively manage pain in cancer patients. This model addresses the needs of patients, healthcare providers, and the healthcare system, aiming to enhance and support pain self-management.

Investigation of L-carnitine effects on CD44+ cancer stem cells from MDA-MB-231 breast cancer cell line as anti-cancer therapy.

Breast cancer stem cells (BCSCs) are a small subpopulation of breast cancer cells, capable of metastasis, recurrence, and drug resistance in breast cancer patients. Therefore, targeting BCSCs appears to be a promising strategy for the treatment and prevention of breast cancer metastasis. Mounting evidence supports the fact that carnitine, a potent antioxidant, modulates various mechanisms by enhancing cellular respiration, inducing apoptosis, and reducing proliferation and inflammatory responses in tumor cells. The objective of this study was to investigate the impact of L-carnitine (LC) on the rate of proliferation and induction of apoptosis in CD44+ CSCs. To achieve this, the CD44+ cells were enriched using the Magnetic-activated cell sorting (MACS) isolation method, followed by treatment with LC at various concentrations. Flow cytometry analysis was used to determine cell apoptosis and proliferation, and western blotting was performed to detect the expression levels of proteins. Treatment with LC resulted in a significant decrease in the levels of p-JAK2, p-STAT3, Leptin receptor, and components of the leptin pathway. Moreover, CD44+ CSCs-treated cells with LC exhibited a reduction in the proliferation rate, accompanied by an increase in the percentage of apoptotic cells. Hence, it was concluded that LC could potentially influence the proliferation and apoptosis of CD44+ CSC by modulating the expression levels of specific protein.

Blaming in women with breast cancer subjected to intimate partner violence: A hermeneutic phenomenological study.

Objective: The present study was conducted to determine the blaming experiences of women with breast cancer subjected to intimate partner violence (IPV). Methods: This hermeneutic phenomenological study explored blaming experiences of women with breast cancer subjected to IPV. Nine women with a mean age of 47.5 years referred to oncology hospitals in Tabriz (Iran) were interviewed using semi-structured in-depth interviews. Data analysis was performed based on Van Manen's thematic analysis method. Results: The main theme emerged from the data is "blaming as a shifting cognitive judgment" with three subthemes of patient blaming partner, partner blaming patient, and self-blame. Conclusions: The findings of the present study revealed that cognitive judgment shifting could be emerged as different types of blaming in the patients with breast cancer exposed to IPV. It is suggested that oncology nurses heed the psychological needs of women with breast cancer through holistic nursing considering couple and family-centered care.

Pain Self-management Strategies in Patients With Cancer: A Qualitative Study.

Successful pain management in patients with cancer is a significant challenge, and paying more attention to patients' experiences of pain self-management strategies has particular importance. This study aimed to explore pain self-management strategies in Iranian patients with cancer. This qualitative study was conducted on 14 patients with cancer. Data were collected using semistructured interviews and analyzed through the Graneheim and Lundman content analysis approach. Two main categories emerged from data analysis: (1) psychological pain self-management strategies, and (2) behavioral pain self-management strategies. Psychological strategies included pain distraction techniques, spiritual tendencies, increasing social interactions and support networks, pain tolerance and self-control, and resistance to pain. Behavioral strategies included massage and touch, heat and cold therapy, opium (Taryak in Persian) and tobacco use, herbal and home remedies, and proper diet.

RNA interference: Promising approach for breast cancer diagnosis and treatment.

Today, cancer is one of the main health-related challenges, and in the meantime, breast cancer (BC) is one of the most common cancers among women, with an alarming number of incidences and deaths every year. For this reason, the discovery of novel and more effective approaches for the diagnosis, treatment, and monitoring of the disease are very important. In this regard, scientists are looking for diagnostic molecules to achieve the above-mentioned goals with higher accuracy and specificity. RNA interference (RNAi) is a posttranslational regulatory process mediated by microRNA intervention and small interfering RNAs. After transcription and edition, these two noncoding RNAs are integrated and activated with the RNA-induced silencing complex (RISC) and AGO2 to connect the target mRNA by their complementary sequence and suppress their translation, thus reducing the expression of their target genes. These two RNAi categories show different patterns in different BC types and stages compared to healthy cells, and hence, these molecules have high diagnostic, monitoring, and therapeutic potentials. This article aims to review the RNAi pathway and diagnostic and therapeutic potentials with a special focus on BC.

L-Carnitine Reduced Cellular Aging of Bone Marrow Resident C-Kit+ Hematopoietic Progenitor Cells Through Telomere Dependent Pathways.

BACKGROUND: Increased oxygen species levels can induce mitochondrial DNA damage and chromosomal aberrations and cause defective stem cell differentiation, leading finally to senescence of stem cells. In recent years, several studies have reported that antioxidants can improve stem cell survival and subsequently affect the potency and differentiation of these cells. Finding factors, which reduce the senescence tendency of stem cells upon expansion, has great potential for cellular therapy in regenerative medicine. This study aimed to evaluate the effects of L-carnitine (LC) on the aging of C-kit+ hematopoietic progenitor cells (HPCs) via examining the expression of some signaling pathway components. METHODS: For this purpose, bone marrow resident C-kit+ HPCs were enriched by the magnetic-activated cell sorting (MACS) method and were characterized using flow cytometry as well as immunocytochemistry. Cells were treated with LC, and at the end of the treatment period, the cells were subjected to the realtime PCR technique along with a western blotting assay for measurement of the telomere length and assessment of protein expression, respectively. RESULTS: The results showed that 0.2 mM LC caused the elongation of the telomere length and increased the TERT protein expression. In addition, a significant increase was observed in the protein expression of p38, p53, BCL2, and p16 as key components of the telomere-dependent pathway. CONCLUSION: It can be concluded that LC can increase the telomere length as an effective factor in increasing the cell survival and maintenance of the C-kit+ HPCs via these signaling pathway components.

Engineered nanoparticles as emerging gene/drug delivery systems targeting the nuclear factor-κB protein and related signaling pathways in cancer.

The transcription factor nuclear factor-κB (NF-κB) is a critical regulator of the immune response, inflammation, cell growth, and survival. Canonical and non-canonical pathways, two NF-κB pathways, are activated through diverse stimulators and receptors. NF-κB activity is dysregulated in various inflammation-related diseases and cancers. It was found that the persistent NF-κB activity has a major role in proliferation, apoptosis inhibition, metastasis, and cell cycle disruption in cancer cells and also the survival of cancer stem cells (CSCs) within the tumors. Therefore, suppression of the NF-κB pathway could be a promising therapeutic target for cancer therapy. Different biological inhibitors (e.g., peptides, small molecules, antisense oligonucleotides (ASOs), and antibodies (Abs)) have been demonstrated to inhibit the NF-κB pathway. Low stability in the circulation system, weak availability, and poor cellular uptake of some inhibitors limit their therapeutic applications. To address these drawbacks nanocarrier systems are often formulated and applied in drug delivery as an effective therapeutic approach. Targeted nanosystems (i.e., small molecules, peptides, Abs and Aptamers (Aps) conjugated nanocarriers), as well as smart responsive nanocarriers, can improve the efficiency of therapeutics while reducing the off-target toxicity. This review describes the NF-κB signaling pathways and mechanisms of their over-activation in tumor initiation and progression. The NF-κB inhibitors and their clinical applications are also discussed. It also overviews different nanocarriers used as robust vehicles for the delivery of NF-κB inhibitors and anti-tumor agents to improve the bioavailability of drugs and selective targeting of cancer cells to repress NF-κB activity in tumor cells.

Bisphosphonates and Prevention of the Perimenopausal Breast Cancer Recurrence: A Systematic Review and Meta-Analysis.

PURPOSE: Bisphosphonates (BPs) have a powerful effect on reducing bone resorption and improving the survival of patients with breast cancer. We aimed to investigate the impact of BP treatment on the prevention of recurrence, metastasis, and death of breast cancer survivors in the perimenopausal period. METHODS: The search strategy aimed to identify both published and unpublished studies in PubMed, Web of Science, Scopus, Embase, ProQuest, and Google Scholar in March 2021. Two independent reviewers assessed quantitative papers selected for retrieval for methodological validity before being included in the review using standardized critical appraisal instruments from the Joanna Briggs Institute (JBI) Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI). Statistical meta-analysis was performed using Review Manager (RevMan) 5.4 statistical software when the data were homogenous. Meta-analysis was performed by calculating the effect size (hazard ratio; HR) and 95% confidence intervals (CIs). RESULTS: Twenty-one studies were eligible for this systematic review and meta-analysis. The overall The HRs for disease-free survival (DFS) and overall survival (OS) in women who received BPs were 0.89 (95% CI, 0.83-0.97; p = 0.005), and 0.75 (95% CI, 0.63-0.89; p = 0.001), respectively. The results showed that BPs had a significant effect on the prevention of locoregional (HR, 0.64; 95% CI, 0.42-0.97; p = 0.04), bone (95% CI, 0.74-0.95; p ≤ 0.001), and distant metastases (HR, 0.77; 95% CI, 0.62-0.94; p = 0.01). In the subgroup analysis based on study design, the only insignificant HR in the included randomized controlled trials (RCTs) was that of locoregional metastasis. CONCLUSION: Although BPs have a promising effect on DFS, OS, and bone metastasis of perimenopausal women survivors of breast cancer, more RCTs are needed to evaluate their effect on other survivors' outcomes.

Recent advances in the production, reprogramming, and application of CAR-T cells for treating hematological malignancies.

As genetically engineered cells, chimeric antigen receptor (CAR)-T cells express specific receptors on their surface to target and eliminate malignant cells. CAR proteins are equipped with elements that enhance the activity and survival of T cells. Once injected, CAR-T cells act as a "living drug" against tumor cells in the body. Up to now, CAR-T cell therapy has been demonstrated as a robust adoptive cell transfer (ACT) immunotherapeutic modality for eliminating tumor cells in refractory hematological malignancies. CAR-T cell therapy modality involves several steps, including the collecting of the blood from patients, the isolation of peripheral blood mononuclear cells (PBMCs), the enrichment of CD4+/CD8+ T cell, the genetic reprogramming, the expansion of modified T cells, and the injection of genetically engineered T cells. The production of CAR-T cells is a multi-step procedure, which needs precise and safety management systems, including good manufacturing practice (GMP), and in-line quality control and assurance. The current study describes the structure of CARs and concentrates on the next generations of CARs that are engaged in enhancing the anti-tumor responses and safety of the engineered T cells. This paper also highlights the important concerns in quality control and nonclinical research of CAR-T cells, as well as general insights into the manufacture, reprogramming, and application of CAR-T cells based on new and enhanced techniques for treating hematological malignancies. Besides, the application of the CRISPR-Cas9 genome editing technology and nanocarrier-based delivery systems containing CAR coding sequences to overcome the limitations of CAR-T cell therapy has also been explained.

The analysis of breast cancer survival in East Azerbaijan province of Iran; prognostic impact of chemotherapy and hormone therapy protocols.

BACKGROUND: The global cancer pattern indicated that there were about 2.3 million newly diagnosed breast cancer cases in 2020 worldwide, and was the most common cancer incident in the world. The aim of the study was to assess the prognostic impact of various treatment modalities and cancer-specific overall and disease-free survival rates. METHODS: One, 5-, 10-, and 15 -years survival rates were calculated; furthermore, overall survival (OS) and disease free survival (DFS) rates were obtained using Kaplan Meier method. To assess the effects of different treatment methods and all clinico-pathological variables with OS and DFS, cox-regression method was used to achieve adjusted hazard ratios of mortality and recurrence rates. RESULTS: During the study period, 504 primary breast cancer cases were evaluated, with mean age of 49.69(± 10.68) years. The one, 5-, 10-, and 15- year survival rates were 98.21%, 87.39%, 68.17% and, 60.60%, respectively. Tamoxifen + GnRh Agonist and Tamoxifen protocols decreased the hazard of relapse 46% and 84%, respectively. The best one-year OS was obtained for patients treated with Tamoxifen with an aromatase inhibitor (AI) for about 100% overall survival rate. The breast cancer mortality rate was lower than relapse rate in the first and 5thyears of disease, but 10- and 15- year mortality were higher than 10- and 15 -year relapse rates. CONCLUSION: Our results revealed better overall survival and disease- free survival among primary breast cancer patients in East Azerbaijan; consequently, this underscores establishing and using better chemotherapy and hormone therapy protocols and sufficient follow-ups.

Hematopoietic Stem Cells Characteristics: From Isolation to Transplantation.

Hematopoietic stem cells (HSCs) have self-renewal as well as pluripotency properties and are responsible for producing all types of blood cells. These cells are generated during embryonic development and transit through various anatomical niches (bone marrow microenvironment). Today, they are easily enriched from some sources, including peripheral blood, bone marrow, and umbilical cord blood (UCB). HSCs have been used for many years to treat a variety of cancers and blood disorders such as various types of leukemia, lymphoma, myelodysplastic, myeloproliferative syndromes, etc. Although almost 50 years have passed since the discovery of stem cells and numerous investigations on cell therapy and regenerative medicine have been made, further studies need to be conducted in this regard. This manuscript review the history, location, evolution, isolation, and therapeutic approaches of HSCs.

Barriers to cancer pain management from the perspective of patients: A qualitative study.

AIM: The aim of this study was to explore the barriers to effective pain management in Iranian people with cancer. DESIGN: A qualitative descriptive design was used. METHODS: This qualitative descriptive study was performed on 14 people with cancer. Data were collected using semi-structured interviews and analysed by Graneheim and Lundman's content analysis method. RESULTS: Four main categories emerged in relation to barriers to pain management from the perspective of people with cancer. Categories included 1) accepting and enduring divine pain, 2) negative attitudes towards the effectiveness of analgesics, 3) patients' low knowledge of pain self-management methods and 4) neglected pain management. Barriers to pain management are multidimensional in nature consisting of patients, healthcare providers and system components. Therefore, attempts should be focused on the education of patients and healthcare providers about pain management and eliminating the shortcomings of the healthcare system.

Fatigue and Its Related Factors Among Iranian Cancer Survivors.

Introduction: Cancer-related fatigue (CRF) is one of the major problems experienced by cancer patients. Identifying the prevalence and factors associated with CRF may be effective in designing appropriate interventions to reduce this problem. This study aimed to examine the prevalence of CRF and its related factors among Iranian cancer survivors. Methods: The samples of this descriptive cross-sectional study included 131 cancer survivors referred to outpatient clinic of Shahid Gazi Hospital affiliated to Tabriz University of Medical Sciences. Brief fatigue inventory (BFI) questionnaire was used for data collection. The data were analyzed using SPSS software version 13, descriptive statistics, and regression analysis. Results: The mean (SD) fatigue score was 6.41 (1.68) and 89% of survivors reported that they had suffered from CRF. The factors affecting CRF included blood pressure, diabetes mellitus, anemia, serum levels of blood urea nitrogen (BUN), marital status, type of cancer, and physical activity. Conclusion: High level of CRF in cancer survivors requires special attention and designing effective interventions through considering the identified factors associated with CRF.

Home Care Nurses' Attitude Towards and Knowledge of Home Palliative Care in Iran: A Cross-Sectional Study.

BACKGROUND: Chronic and cancer diseases are expected to rise with the growing population of the elderly in the world. Home palliative care might be a possible solution for improving these patients' quality of life; therefore, the present study sets out to investigate home care nurses' attitude towards and knowledge of home palliative care. MATERIALS AND METHODS: This is a descriptive cross-sectional study (2018-19), in which 168 home care nurses and nursing assistants in East Azerbaijan Province (Iran) were included (2018). The questionnaire used was specifically designed by Shimizu et al. in 2016 for determining the nurses' attitude towards and knowledge of home care. Data analysis was carried out using descriptive and inferential statistics (T-test and ANOVA). RESULTS: In this study, 95 (56.60%) and 113 (67.90%) of the participants were found to have negative attitudes and limited knowledge, respectively. The other participants seemed to have neutral attitudes towards and average knowledge of home palliative care. The Mean (SD) attitude score on terminal home care was estimated 2.33 (0.83), and the knowledge score on dying care was calculated 41.76%, which were the lowest in comparison with the scores of other dimensions. CONCLUSIONS: The home care nurses' attitude towards and knowledge of home palliative care were found to be negative and limited, respectively, which underscores the need to endeavor to improve the attitude towards home care and the knowledge of dying care.