Anthracycline-Induced Cardiomyopathy in Cancer Survivors: Management and Long-Term Implications.

Recent advancements in personalized treatments, such as anthracycline chemotherapy, coupled with timely diagnoses, have contributed to a decrease in cancer-specific mortality rates and an improvement in cancer prognosis. Anthracyclines, a potent class of antibiotics, are extensively used as anticancer medications to treat a broad spectrum of tumors. Despite these advancements, a considerable number of cancer survivors face increased risks of treatment complications, particularly the cardiotoxic effects of chemotherapeutic drugs like anthracyclines. These effects can range from subclinical manifestations to severe consequences such as irreversible heart failure and death, highlighting the need for effective management of chemotherapy side effects for improved cancer care outcomes. Given the lack of specific treatments, early detection of subclinical cardiac events post-anthracycline therapy and the implementation of preventive strategies are vital. An interdisciplinary approach involving cardiovascular teams is crucial for the prevention and efficient management of anthracycline-induced cardiotoxicity. Various factors, such as age, gender, duration of treatment, and comorbidities, should be considered significant risk factors for developing chemotherapy-related cardiotoxicity. Tools such as electrocardiography, echocardiography, nuclear imaging, magnetic resonance imaging, histopathologic evaluations, and serum biomarkers should be appropriately used for the early detection of anthracycline-related cardiotoxicity. Furthermore, understanding the underlying biological mechanisms is key to developing preventive measures and personalized treatment strategies to mitigate anthracycline-induced cardiotoxicity. Exploring specific cardiotoxic mechanisms and identifying genetic variations can offer fresh perspectives on innovative, personalized treatments. This chapter aims to discuss cardiomyopathy following anthracycline therapy, with a focus on molecular mechanisms, preventive strategies, and emerging treatments.

Effects of miR-330 restoration on pancreatic cancer cells oncogenesis.

BACKGROUND: Inappropriate expressions of various miRNAs have reported in different human malignancies. Evidence suggested that miR-330 may play as both onco-miR and/or tumor suppressor-miR in different cancers. In the present study, we evaluated effects of miR-330 on proliferation and migration of pancreatic cancer (PC) cells as well as underlying molecular mechanisms. DESIGN: The expression of miR-330 was evaluated in clinical tissue samples of patients with PC. Transfection of the PC cells (PANC-1) by miR-330 was conducted by pCMV vector. The cancer-related genes expression was investigated in mRNA and protein level following transfection of the PC cells. Furthermore, the PC cells viability, invasion, migration, mitochondrial membrane potential, apoptosis, autophagy, and cell cycle profile were investigated after transfection by miR-330. RESULTS: The results indicated that expression of miR-330 downregulated in patients with PC. Stable increase of miR-330 expression after transfection in PC cells reduces viability, mitochondrial membrane potential, invasion, and migration. Further assessments demonstrated that upregulation of miR-330 increases apoptosis and autophagy percentage in the PC cells. Moreover, a cell cycle arrest was observed in G1, Sub-G1, and S phases following transfection of the PC cells. These findings can be explained by modified mRNA and protein expression of apoptosis- and metastasis-related genes. CONCLUSION: Our study suggested that miR-330 acts as a tumor suppressor in PC cells, and revealed that upregulation of miR-330 may provide an effective therapeutic approach for overcoming progression and metastasis in patients with PC.

The Potential Role of Intestinal Stem Cells and Microbiota for the Treatment of Colorectal Cancer.

Colorectal cancer is a global health concern with high incidence and mortality rates. Conventional treatments like surgery, chemotherapy, and radiation therapy have limitations in improving patient survival rates. Recent research highlights the role of gut microbiota and intestinal stem cells in maintaining intestinal health and their potential therapeutic applications in colorectal cancer treatment. The interaction between gut microbiota and stem cells influences epithelial self-renewal and overall intestinal homeostasis. Novel therapeutic approaches, including immunotherapy, targeted therapy, regenerative medicine using stem cells, and modulation of gut microbiota, are being explored to improve treatment outcomes. Accordingly, this chapter provides an overview of the potential therapeutic applications of gut microbiota and intestinal stem cells in treating colorectal cancer.

Isolation and Phenotypic Characterization of Tumor-Infiltrating NK Cells in Skin Carcinoma.

In oncological research, the function of tumor-infiltrating natural killer (NK) cells in skin carcinoma presents a viable avenue for novel therapeutic methods. NK cells are essential to the body's defense against malignancies, including skin cancer, and are especially important in more sophisticated cancer immunotherapies such as vaccinations containing dendritic cells. The deadliest type of skin cancer, malignant melanoma, still has a poor prognosis even with advancements in early-stage therapies, which emphasizes the need for novel therapeutic strategies. NK cells from human melanoma metastases were subjected to single-cell RNA-seq analysis, which demonstrated notable variations in the transcriptional programs of tumor-infiltrating and circulating NK cells. Different transcriptional states are displayed by NK cells that have invaded tumors, indicating that they are functionally specialized in areas like chemokine production and cytotoxicity. These results emphasize the functions of NK cells in recruiting other significant immune cell types, such as cross-presenting dendritic cells, and in direct cytotoxicity against malignant cells. Investigating NK cells that infiltrate tumors in skin carcinomas presents a viable approach to comprehending and may be modifying the immune environment surrounding these cancers. It is essential to comprehend the distinct characteristics and roles of NK cells inside the tumor microenvironment in order to create more potent immunotherapeutic approaches to treat skin cancer. In order to perhaps open the door for new directions in cancer immunotherapy, the project intends to establish a thorough technique for the isolation and thorough phenotypic characterization of tumor-infiltrating NK cells in skin carcinoma.

Management of Fluoropyrimidine-Induced Cardiac Adverse Outcomes Following Cancer Treatment.

Advancements in cancer treatments have improved survival rates but have also led to increased cardiotoxicities, which can cause adverse cardiovascular events or worsen pre-existing conditions. Herein, cardiotoxicity is a severe adverse effect of 5-fluorouracil (5-FU) therapy in cancer patients, with reported incidence rates ranging from 1 to 20%. Some studies have also suggested subclinical effects and there are reports which have documented instances of cardiac arrest or sudden death during 5-FU treatment, highlighting the importance of timely management of cardiovascular symptoms. However, despite being treated with conventional medical approaches for this cardiotoxicity, a subset of patients has demonstrated suboptimal or insufficient responses. The frequent use of 5-FU in chemotherapy and its association with significant morbidity and mortality indicates the need for a greater understanding of 5-FU-associated cardiotoxicity. It is essential to reduce the adverse effects of anti-tumor medications while preserving their efficacy, which can be achieved through drugs that mitigate toxicity associated with these drugs. Underpinning cardiotoxicity associated with 5-FU therapy also has the potential to offer valuable guidance in pinpointing pharmacological approaches that can be employed to prevent or ameliorate these effects. The present study provides an overview of management strategies for cardiac events induced by fluoropyrimidine-based cancer treatments. The review encompasses the underlying molecular and cellular mechanisms of cardiotoxicity, associated risk factors, and diagnostic methods. Additionally, we provide information on several available treatments and drug choices for angina resulting from 5-FU exposure, including nicorandil, ranolazine, trimetazidine, ivabradine, and sacubitril-valsartan, which have demonstrated potential in mitigating or protecting against chemotherapy-induced adverse cardiac effects.

Development of CAR-NK Cells Targeting cSCC-Specific Antigens for Precision Immunotherapy.

Cutaneous squamous cell carcinoma (cSCC), a non-melanoma skin cancer that is frequently diagnosed, is distinguished by its propensity for aggressive behavior, frequent poor response to standard therapy, and capacity to metastasize to distant areas. Utilizing the body's natural immune defense mechanisms, particularly through the use of chimeric antigen receptor (CAR) technology, is receiving increasing attention in the dynamic field of oncological therapies. Although T cells have received most of the attention, this strategy has proven to be highly effective in battling some blood-related malignancies. However, there are considerable challenges when using this method in the context of solid tumors. The innate immune system's natural killer (NK) cells are essential parts because they have the ability to detect and destroy cancer cells. CAR-NK cells are a very promising approach because they combine the natural cytotoxic properties of natural killer (NK) cells with the precise targeting skills of chimeric antigen receptor (CAR) technology. With the use of this integrated strategy, the intrinsic diversity of cutaneous squamous cell carcinoma (cSCC) tumors may be successfully targeted, increasing treatment effectiveness and lowering the risk of tumor recurrence. This tactic is improved by the development of dual-specificity chimeric antigen receptors (CARs), which fully resolve the antigen presentation heterogeneity among tumor cells. In conclusion, the use of CAR-NK cells that precisely target cSCC-specific antigens has the potential to drastically transform therapy approaches for cSCC as well as other difficult solid tumors as oncological research advances. In order to create chimeric antigen receptor (CAR)-natural killer (NK) cells that particularly target antigens linked to cutaneous squamous cell carcinoma (cSCC), the goal of this protocol is to present a detailed method. The ultimate objective is to lay the groundwork for the development of precision immunotherapy.

Targeted co-delivery of methotrexate and chloroquine via a pH/enzyme-responsive biocompatible polymeric nanohydrogel for colorectal cancer treatment.

Application of conventional chemotherapy regardless of its unique effectiveness have been gradually being edged aside due to limited targeting capability, lack of selectivity and chemotherapy-associated side effects. To this end, colon-targeted nanoparticles via combination therapy have shown great therapeutic potential against cancer. Herein, pH/enzyme-responsive biocompatible polymeric nanohydrogels based on poly(methacrylic acid) (PMAA) containing methotrexate (MTX) and chloroquine (CQ) were fabricated. PMAA-MTX-CQ exhibited high drug loading capacity of which MTX was 4.99% and was CQ 25.01% and displayed pH/enzyme-triggered drug release behavior. Higher CQ release rate (76%) under simulated acidic microenvironment of tumor tissue whereas 39% of CQ was released under normal physiological conditions. Intestinally, MTX release was facilitated in the presence of proteinase K enzyme. TEM image demonstrated spherical morphology with particle size of less than 50 nm. In vitro and in vivo toxicity assessments indicated that developed nanoplatforms possessed great biocompatibility. These nanohydrogels did not cause any adverse effects against Artemia Salina and HFF2 cells (around 100% cell viability) which highlight the safety of prepared nanohydrogels. There was no death in mice received different concentrations of nanohydrogel through oral administration and less than 5% hemolysis was found in red blood cells incubated with PMAA nanohydrogels. In vitro anti-cancer results showed that combination therapy based on PMAA-MTX-CQ can effectively suppress the growth of SW480 colon cancer cells (29% cell viability) compared to monotherapy. Altogether, these findings suggest that pH/enzyme-responsive PMAA-MTX-CQ could effectively inhibit cancer cell growth and progression via site-specific delivery of its cargo in a safe and controlled manner.

How to establish infrastructures to achieve more efficient regenerative medicine?

The field of regenerative medicine (RM) as an innovative technology has the ability to affect the healthcare system. It develops a variety of techniques through stem cell biology, genetics, bioengineering, biomaterial science, and tissue engineering to replace or restore the role of lost, disabled, or aging cells in the human body. However, the field's proficiency has still been underwhelming at the clinical trial level. This could be due to the innovation of such technologies, as well as their incredible nature. Therefore, managing the infrastructure framework for the safe and efficient application of the aforementioned field of science would help in the process of progress. In this context, the current review focuses on how to establish infrastructures for more effective RM.

Immunological evaluation of patients with 2019 novel coronavirus pneumonia: CD4+ and CD16+ cells may predict severity and prognosis.

PURPOSE: Available but insufficient evidence shows that changes may occur in the immune system following coronavirus disease 2019 (COVID-19). The present study aimed at evaluating immunological changes in patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pneumonia compared with the control group. METHOD: The present study was performed on 95 patients with COVID-19 (32 severe and 63 moderate cases) and 22 healthy controls. Relationship between immune cells, disease severity and lung involvement was assessed. Binary logistic regression and ROC curve tests were used for statistical analysis. RESULTS: A significant decrease was observed in CD20+ cell counts of the patients. To differentiate patients from healthy individuals, the cutoff point for the CD4+ cell count was 688 /µL, sensitivity 0.96, and specificity 0.84. An increase in CD4+ cells reduces the odds of severe disease (odds ratio = 0.82, P = 0.047) and death (odds ratio = 0.74, P = 0.029). CD4+ cells play a pivotal role in the severity of lung involvement (P = 0.03). In addition to CD4+ cells, Fc gamma receptor III (FcγRIII) (CD16) also played a significant prognosis (odds ratio = 0.55, P = 0.047). In severe cases, C-reactive protein, Blood urea nitrogen, and Creatine phosphokinase levels, as well as neutrophil counts, were significantly higher than those of moderate ones whereas lymphocyte count in severe cases was lower than that of moderate ones. CONCLUSION: The number of total T-cells and B-cells in patients with COVID-19 was lower than that of controls; however, their NK cells increased. FcγRIII and CD4+ cells are of great importance due to their association with COVID-19 prognosis.

Comparison of High-Resolution Melting (HRM) Analysis with Direct Sequencing for the Detection of DNMT3A Mutations in AML Patients.

OBJECTIVE: Acute myeloid leukemia (AML) is caused by abnormal gene expression following mutations. Many of the mutations in AML lead to gene instability and poor response to treatment. Among these mutations, DNMT3A mutation is exceedingly important due to its major role in methylation and its effect on the expression of other genes. Aberrant methylation due to DNMT3A mutations that mostly occur in exon 23, affects the overall survival (OS) of patients with AML and myelodysplastic syndromes (MDS) showing the importance of identification of these mutations. According to the association of these mutations with short overall survival and disease progression in AML patients, we aimed to investigate DNMT3A gene exon 23 mutations using HRM. METHODS: Fifty peripheral blood samples were taken from patients with AML. Mononuclear cells were isolated by ficoll method, and DNA was extracted. Then, mutation detection was detected using the HRM method. Efficacy of the HRM method in mutation detection was compared with direct sequencing method as gold standard. RESULTS: Mutations in codon 23 of the DNMT3A gene were detected in 5 patients (10%). All of the detected mutations were missense type. A comparison between direct sequencing and HRM analysis demonstrated full concordance of mutation detection. CONCLUSION: According to the full consistency between the HRM and direct sequencing methods, HRM is suggested to be adopted as an alternative for the common time-consuming methods in detecting the gene mutations.

Post-COVID-19 hematologic complications: a systematic review.

INTRODUCTION: COVID-19 crisis continues around the world. Some patients developed complications after the disease, which have been reported in limited studies. The aim of this study is to comprehensively assess the post-COVID hematologic complications in patients. AREAS COVERED: We searched PubMed, Scopus, and Google Scholar between January 2020 and August 2021 using related keywords. Evaluation of the article was performed by two independent researchers. The extracted data included the number of patients, age, type of hematological complication, duration of follow-up, response to treatment and prognosis. EXPERT OPINION: Sixty-five articles reported post-COVID hematologic complications. The most frequent hematologic complication in COVID-19 patients is thromboembolic events, which often occur in two forms: deep vein thrombosis (DVT) and pulmonary embolism (PE). In a group of patients after the diagnosis of COVID-19, a significant decrease in platelets was observed, which was attributed to the ITP induced by COVID-19. Hemolytic anemia and aplastic anemia have also been reported rarely in patients. Finally, post-COVID hematologic complications appear to go beyond thromboembolic events. Although these complications have rarely been reported, searching for methods to identify susceptible patients and prevent these complications could be the subject of future research.

Regulatory T Cells in Immunopathogenesis and Severity of COVID-19: A Systematic Review.

BACKGROUND: Severe cases of coronavirus disease 2019 (COVID-19) often experience hyper-inflammatory reactions, acute respiratory distress syndrome (ARDS), blood clotting, and organ damage. The most prominent immunopathology of advanced COVID-19 is cytokine release syndrome, or "cytokine storm" which is attributed to a defect of immune-regulating mechanisms. This study aimed to evaluate the role of regulatory T cells (Tregs) as one of the main cells that maintain immune homeostasis. METHODS: A systematic search was performed on PubMed, Scopus and Google Scholar. All English articles related to Treg's role in COVID-19 were extracted and evaluated by two researchers independently. Study eligibility was assessed based on modified Evidence-based librarianship (EBL) checklist. RESULTS: Nineteen eligible studies comparing Treg cells in COVID-19 patients with the control group or comparing alterations of this cell in severe and moderate patients were evaluated. Currently, there is no consensus regarding the increase or decrease of Tregs in COVID-19 patients compared to the control group. However, it was observed that Tregs in severe COVID-19 patients were significantly lower than moderate patients, resulting in uncontrolled inflammation and cytokine storm. CONCLUSION: Regulatory T cells can be one of the determinants of disease severity and prognosis in patients with COVID-19 by inhibiting rampant inflammation and preventing cytokine storms.

Rapid Detection of N-RAS Gene Common Mutations in Acute Myeloid Leukemia (AML) Using High Resolution Melting (HRM) Method.

OBJECTIVE: Acute myeloid leukemia is caused by the clonal proliferation of undifferentiated myeloid hematopoietic precursors. AML prognosis is highly involved in the treatment response and is determined by mutations in several genes such as N-RAS. This study aims to identify the distribution of common N-RAS mutations (codons 12, 13, and 61) in AML patients using the HRM method and confirm this method's efficiency for mutation detection by comparing its results with the sequencing data as the Gold standard method. METHODS: Peripheral blood samples were taken from 50 newly diagnosed AML patients. Mononuclear cells were isolated from samples, and DNA was extracted. Then, mutation detection was investigated using the HRM method. Efficacy of the HRM method in mutation detection was determined in comparison with direct sequencing. RESULTS: N-RAS mutations were detected in 7 of the 50 samples (14%). Most of the mutations were found in codon 12 (57.14%), and 28.57% and 14.28% of mutations were in codons 61 and 13, respectively. There was no statistically significant association between patients' demographic data and HRM results. CONCLUSION: According to mutation detection results and the HRM results confirmation with the sequencing method, this method can be introduced as an efficient, low-cost, and fast method for detecting common mutations.

Association of MALAT1 expression in gastric carcinoma and the significance of its clinicopathologic features in an Iranian patient.

AIM: The aim of this study was to evaluate the expression of MALAT1 and the relationship between its expression with clinical characteristics in an Iranian gastric cancer patient. BACKGROUND: Long non-coding RNAs (LncRNAs) play critical roles in the initiation and development of gastric cancer. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a highly conserved lncRNA and plays key roles in various types of human cancer. However, our understanding of the role of lncRNAs in the occurrence and development of gastric cancer is not fully clear. METHODS: This cross-sectional study was performed on 41 gastric tumor tissue samples with matched normal adjacent tumor tissues. The RNA level of lncRNA MALAT1 gene was assessed using quantitative Real-time polymerase chain reaction. B2M was used as an internal control. The 2 -ΔΔCq method was adopted to determine expression fold changes. RESULTS: A significant association was observed between the levels of MALAT1 in gastric tumor tissues compared with normal adjacent tissues (mean= 1.558, p= 0.014). In addition, clinicopathologic data on MALAT1 RNA expression levels in gastric cancer tissues was evaluated. No significant association was observed between the relative expression of MALAT1 and the stage, grade, H. pylori infection, and tumor size groups among gastric cancer patients (p= 0.82, p= 0.904, p= 0.407, and p= 0.701, respectively). CONCLUSION: The current results showed that MALAT1 has a significant association in gastric cancer. The expression of MALAT1 may be used as a diagnostic biomarker for monitoring gastric cancer patients.

Efficacy and Safety of Proposed Bevacizumab Biosimilar BE1040V in Patients With Metastatic Colorectal Cancer: A Phase III, Randomized, Double-blind, Noninferiority Clinical Trial.

PURPOSE: The purpose of this study was to compare the efficacy and safety of a proposed bevacizumab biosimilar to those of the reference product in patients with metastatic colorectal cancer (mCRC). METHODS: This Phase III, multicenter, randomized, double-blind (patient- and assessor-blind), active-controlled, 2-armed, parallel-group, noninferiority trial was conducted in patients with histologically verified colorectal cancer with evidence of at least 1 metastasis. Patients with mCRC were randomized 2:1 to receive 5 mg/kg IV of either study drug plus FOLFIRI-3 (with repeated irinotecan 100 mg/m2 60-min infusion on day 3) or the reference drug plus FOLFIRI-3 every 2 weeks for 1 year. Progression-free survival (PFS) was the primary end point, and overall survival, objective response rate, and time to treatment failure as well as safety and immunogenicity were secondary end points. The population assessable for PFS was per protocol, and the intention-to-treat population was used for sensitivity analysis. Safety was assessed based on reports of adverse events, laboratory test results, and vital sign measurements. FINDINGS: A total of 126 patients were enrolled; PFS values in the biosimilar and reference arms were 232 days (7.7 months) and 210 days (7 months), respectively (P = 0.47). The hazard ratio of the biosimilar arm versus the reference arm was 0.79 in the per-protocol population (90% CI, 0.46-1.35; P = 0.47). The upper limit for the 2-sided 90% CI was lower than the margin of 1.44, indicating that the biosimilar drug was noninferior to the reference drug. The hazard ratio for overall survival in the intent-to-treat population was 0.99 (95% CI, 0.55-1.80; P = 0.99). The difference between other efficacy end points among the groups was not statistically significant. No significant difference was observed in the comparison of the two arms for safety. The antidrug antibody was positive in 1 patient in each arm. IMPLICATIONS: The proposed biosimilar BE1040V was noninferior to the reference product in terms of efficacy in the treatment of mCRC, and tolerability was comparable between the 2 drugs. ClinicalTrials.gov identifier: NCT03288987.

Effectiveness of adjuvant chemotherapy in patients with Stage II colorectal cancer: A multicenter retrospective study.

BACKGROUND: Adjuvant chemotherapy (ACT) for patients with Stage II colorectal cancer (CRC) is an area of controversy in oncology. International guidelines recommend the use of ACT in patients with specific high-risk features. This study aimed to investigate the effectiveness of ACT in improving survival in patients with and without high-risk features. MATERIALS AND METHODS: A total of 225 patients with Stage II CRC who underwent primary tumor resection were included in this study. Patients with one or more high-risk features including T4 tumor, poor differentiation, lymphovascular invasion, perineural invasion, bowel obstruction, local perforation, positive resection margins, or suboptimal lymph node sampling (fewer than 12 nodes) were classified as high risk. The survival analysis was performed between patients who only received curative surgery and those received single-agent (5-fluorouracil [5-FU] and leucovorin [LV] or capecitabine) or multiagent ACT (oxaliplatin and 5-FU + LV or oxaliplatin and capecitabine). RESULTS: The 5-year overall survival (OS) rate was 88.4%, and the 5-year disease-free survival (DFS) rate was 80.4%. The 5-year OS and DFS rates improved insignificantly with ACT (89.8% vs. 81.2%, P = 0.59 and 81.3% vs. 74.6%, P = 0.41, respectively); however, multiagent ACT results to inferior 5-year OS and DFS compared to single-agent ACT (82.1 vs. 92.8%, P = 0.14 and 70.1% vs. 86%, P = 0.07, respectively). ACT was associated with insignificant improved OS and DFS in both high-risk and low-risk groups, but high-risk patients who received multiagent ACT had a significant inferior OS and DFS in comparison with those received single-agent ACT. T4 tumor and obstruction were independent poor prognostic factors affecting OS and DFS. CONCLUSION: In our population, the improvement of OS and DFS with ACT was not statistically significant in high-risk and low-risk patients with Stage II CRC.

Retrospective Analysis of 345 Multiple Myeloma Cases: An Investigation from 2 Institutions.

BACKGROUND: Multiple myeloma (MM) accounts for a substantial mortality rate among hematological cancers. The prognosis of the disease has been noticeably changed during the past 2 decades. This study reports a retrospective analysis of 345 MM cases from 2 cancer centers. METHODS: Medical records of 345 MM cases were analyzed in retrospect. Diagnosis of MM was defined in presence of at least 10% plasma cells in bone marrow biopsy and one of the CRAB findings (hypercalcemia, renal failure, anemia and myeloma bone lesions). Survival analysis was performed using Kaplan-Meier method, and the effects of prognostic variables were assessed by Cox proportional hazards model. RESULTS: The mean age of the patients was 61.98 ± 11.44 years. Comparing to Mayo Clinic series, our patients were relatively younger and suffered from more advanced disease. By a median follow up time of 45 months, 1- and 5-year overall survival (OS) rates were 78.0% and 35.6%, respectively. Regarding first progression free survival (PFS1), similar rates of 57.7% and 17.0% were observed respectively. In multivariate analysis, hypercalcemia (corrected serum calcium >11 mg/dL), pancytopenia and elevated serum creatinine (Cr) (>2 mg/dL) were found to be independent prognostic factors affecting OS. CONCLUSION: Presentation of MM in Iran which is a developing country, was significantly different from developed countries. This finding might be generalized to other developing countries as well. In addition, vincristine-adriamycin-dexamethasone (VAD) therapy was an inferior protocol compared to bortezomib as first and second lines. Furthermore, pancytopenia was observed in about 9% of the patients and was an independent prognosticator of the disease.

Sixteen Years of Experience with the Treatment of Advanced Colorectal Cancer in Iran; A Report from Three Institutions.

BACKGROUND Colorectal cancer (CRC) is one of the most common cancers worldwide. Recently treatments of advanced CRC have been immensely improved. In this study we reported the current state of advanced CRC in Iran regarding treatment and outcomes from 2000 to 2016. METHODS 370 subjects with stage III or IV of the disease were included in this study. Pathological subtypes other than adenocarcinoma were excluded. Demographics and other relevant clinical data were collected. RESULTS Mean age at diagnosis was 55.4 ± 12.6 years. Significant differences regarding the age, sex, primary tumor complication and location, lymph node involvement, and tumor size were not detected between patients with stage III and IV. Overall survival rate at 5 years was 69.5% (95% confidence interval: 60.8% - 76.6%) and 21.73% (95% CI: 12.46% - 32.70%) for patients with stage III and IV, respectively. Analysis of prognostic factors revealed that tumor grade was an independent factor predicting poorer outcome (poorly differentiated vs. well or moderately differentiated). Furthermore, in stage IV of the disease, IVb subgroup was found to be associated with a poorer outcome compared with stage IVa. CONCLUSION Even with the acceptable survival rates and more effective treatments, it seems that clinicopathological characteristics have yet the most important prognostic effect in advanced CRC.

Effectiveness of modified hyper-CVAD chemotherapy regimen in the treatment of adult acute lymphoblastic leukemia: a retrospective experience.

Several chemotherapy regimens have been developed for the treatment of acute lymphoblastic leukemia (ALL), but relapse still presents the most common obstacles to attaining long-term survival. The hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and prednisolone)/HD MTX and Ara-C (high-dose methotrexate and cytarabine) chemotherapy regimen was first started in the MD Anderson Cancer Center as an intensive regimen for adult patients with ALL. The purpose of this study was to evaluate the effectiveness of a modified hyper-CVAD protocol. We used hyper-CVAD as consolidation/maintenance after remission induction with daunorubicin, vincristine, and prednisolone (and cyclophosphamide for T-cell ALL only) rather than standard hyper-CVAD in order to reduce treatment complications. This study was conducted as a retrospective review of medical records of ALL patients at 501 army hospital, Tehran, Iran, from 2005 to 2015. Three hundred and one patients underwent modified hyper-CVAD chemotherapy regimen. Complete remission and overall survival (OS) rates were measured as primary endpoints. Two hundred and forty-six (81.7%) reached complete remission (CR) during the first 6 months of treatment, and 55 patients (18.3%) did not reach CR. The 5-year OS rate was 51.8% (95% CI (confidence interval): 45.1-57.8%). Modified hyper-CVAD regimen is an efficient intensive chemotherapy regimen for consolidation/maintenance of adults with newly diagnosed ALL and has an acceptable 5-year overall that is comparable to standard hyper-CVAD regimen.

Prevalence of Human T-lymphotropic virus type 1 (HTLV-1) Infection in Patients with Hematologic Disorders and Non-Hematologic Malignancies in a Tertiary Referral Hospital.

BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1) was the first retrovirus identified in human. The current evidence is quite scarce regarding the potential role of HTLV-1 in pathogenesis of hematologic disorders and non-hematologic malignancies. OBJECTIVES: The aim of this study is to evaluate the prevalence of HTLV-1 infection in patients with hematologic disorders and non-hematologic malignancies. METHODS: This cross-sectional study was conducted on 505 cases of definite diagnosis of hematologic disorders including malignancies as well as non-malignant disorders such as polycythemia and myelofibrosis and non-hematologic malignancies referred to the hematology and medical oncology ward at Army Hospital 501 from January 2015 to January 2016. A 3-mL blood specimen was collected from each patient and tested for the presence of anti-HTLV-1 antibodies using enzyme-linked immunosorbent assay (ELISA). Data were analyzed using SPSS software package version 19 (IBM, New York, USA). Data are presented as mean ± SD if normally distributed and otherwise as median (range). RESULTS: Totally, 242 (48%) males and 263 (52%) females with a mean ± SD age of 52.09 ± 16.24 were enrolled in this study. In total, there were 9 (1.78%) cases positive for HTLV-1 infection including 4 males and 5 females. Seven out of 287 (2.4%) patients with hematologic disorders were infected by HTLV-1. In non-hematologic malignancies, 2 out of 211 cases were positive (0.9%). There was no HTLV-1 positive case in 7 patients with both hematologic and non-hematologic disorders. The difference in HTLV-1 infection prevalence between patients with hematologic disorders and non-hematologic malignancies was not statistically significant different (P = 0.31). There was no association between sex and transfusion history with HTLV-1 infection in this population (P = 0.9 and 0.7, respectively). CONCLUSIONS: Our study revealed that the prevalence of HTLV-1 in hematologic disorders is higher than the general population. Further larger prospective studies are recommended to corroborate the current evidence.