Doxorubicin-loaded zymosan nanoparticles: Synergistic cytotoxicity and modulation of apoptosis and Wnt/ß-catenin signaling pathway in C26 colorectal cancer cells.

Zymosan is a ß-glucan isolated from Saccharomyces cerevisiae that could be employed for drug delivery. We synthesized zymosan nanoparticles and measured their structural and morphological properties using XRD, UV-Vis spectroscopy, TEM and AFM. The loading of doxorubicin (DOX) onto the nanoparticles was confirmed by FT-IR, and the DOX release was shown to be pH-dependent. The effect of these agents on C26 cell viability was evaluated by MTT tests and the expression of genes connected with the Wnt/ß-catenin pathway and apoptosis were analyzed by RT-qPCR and Western blotting. Treatments were able to suppress the proliferation of C26 cells, and the zymosan nanocarriers loaded with DOX enhanced the anti-proliferative effect of DOX in a synergistic manner. Zymosan nanoparticles were able to suppress the expression of cyclin D1, VEGF, ZEB1, and Twist mRNAs. Treatment groups upregulated the expression of caspase-8, while reducing the Bax/Bcl-2 ratio, thus promoting apoptosis. In conclusion, zymosan nanoparticles as DOX nanocarriers could provide a more targeted drug delivery through pH-responsiveness, and showed synergistic cytotoxicity by modifying Wnt/ß-catenin signaling and apoptosis.

Emerging roles of miR-145 in gastrointestinal cancers: A new paradigm.

Gastrointestinal (GI) carcinomas are a group of cancers affecting the GI tract and digestive organs, such as the gastric, liver, bile ducts, pancreas, small intestine, esophagus, colon, and rectum. MicroRNAs (miRNAs) are small functional non-coding RNAs (ncRNAs) which are involved in regulating the expression of multiple target genes; mainly at the post-transcriptional level, via complementary binding to their 3'-untranslated region (3'-UTR). Increasing evidence has shown that miRNAs have critical roles in modulating of various physiological and pathological cellular processes and regulating the occurrence and development of human malignancies. Among them, miR-145 is recognized for its anti-oncogenic properties in various cancers, including GI cancers. MiR-145 has been implicated in diverse biological processes of cancers through the regulation of target genes or signaling, including, proliferation, differentiation, tumorigenesis, angiogenesis, apoptosis, metastasis, and therapy resistance. In this review, we have summarized the role of miR-145 in selected GI cancers and also its downstream molecules and cellular processes targets, which could lead to a better understanding of the miR-145 in these cancers. In conclusion, we reveal the potential diagnostic, prognostic, and therapeutic value of miR-145 in GI cancer, and hope to provide new ideas for its application as a biomarker as well as a therapeutic target for the treatment of these cancer.

The Importance of Evaluating Serum Levels of Tumor Markers M2-PK and Inhibin A in Patients Undergoing Colonoscopy.

Despite the use of colonoscopy to detect colon cancer due to its aggressiveness, high cost, and lack of patient compliance, the use of laboratory tests with high accuracy and sensitivity, such as tumor marker M2-PK and Inhibin A is recommended and can be effective for early diagnosis and screening of patients in the early stages. We studied 46 patients admitted it the gastrointestinal ward of Amir al Momenin Hospital and 45 normal (age and sex-matched) subjects as a control group (case-control and retrospective studies). Before the colonoscopy, the level of tumor marker M2-PK in the stool sample and the serum level of Inhibin A were evaluated in patients and the control group. The level of tumor marker M2-PK was significantly higher in the group with hyperplastic polyps and colon cancer (P < .001) than in the control group. At the same time, there was no significant difference in Inhibin A level (P = .054). In the hyperplastic polyps group 73% and in the colorectal cancer group 27% had a positive immunochemical fecal occult blood (IFOBT) result, significantly higher than the control group (P < .001). Evaluation of the level of tumor marker M2-PK in the stool sample in association with the three-time iFOBT test method may be suggested as a quick and noninvasive method for screening and diagnosis of polyps and early stages of colon cancer.

Role of non-coding RNAs in neuroblastoma.

Neuroblastoma is known as the most prevalent extracranial malignancy in childhood with a neural crest origin. It has been widely accepted that non-coding RNAs (ncRNAs) play important roles in many types of cancer, including glioma and gastrointestinal cancers. They may regulate the cancer gene network. According to recent sequencing and profiling studies, ncRNAs genes are deregulated in human cancers via deletion, amplification, abnormal epigenetic, or transcriptional regulation. Disturbances in the expression of ncRNAs may act either as oncogenes or as anti-tumor suppressor genes, and can lead to the induction of cancer hallmarks. ncRNAs can be secreted from tumor cells inside exosomes, where they can be transferred to other cells to affect their function. However, these topics still need more study to clarify their exact roles, so the present review addresses different roles and functions of ncRNAs in neuroblastoma.

Gastrointestinal mucormycosis: A periodic systematic review of case reports from 2015 to 2021.

BACKGROUND: GI mucormycosis (GI) is a rare but highly lethal infection in patients. There is no single comprehensive review of the literature that demonstrates the various clinical aspects of this infection. METHODS: A structured search of PubMed/Medline was used to collect case reports of GI mucormycosis in patients of all ages published between 2015 and November 2021. RESULTS: Eighty-seven cases were identified through PubMed bibliographic database searches, and final analyses were conducted on 70 adults and ten neonatal patients with GI mucormycosis. Asia had the highest number of reported cases, with 46 (57.5%). Neonatal cases had a mortality rate of 70%, while other cases had a mortality rate of 44%. Corticosteroid therapy and diabetes were the most significant risk factors in patients, while 11% were immunocompetent with no apparent underlying condition. COVID-19 positivity was detected in four adult patients. Moreover, neonatal cases included premature and low-weight infants, metabolic acidosis, and malnutrition. Abdominal pain, fever, and GI perforation were the most common signs of infection, while vomiting occurred in 40% of neonatal cases. In 97% of patients, a histopathologic examination was used to detect infection, whereas culture and molecular methods were used in only 28% and 17% of patients, respectively. Surgery plus anti-infection therapy, anti-infection therapy alone, and surgery alone were used in 61%, 28%, and 11% of patients, respectively. Nonetheless, all neonatal patients underwent surgery. Although used in a small number of patients, posaconazole (30%) and isavuconazole (11%) demonstrated high efficacy in treating patients. CONCLUSION: GI mucormycosis is a rare but highly lethal disease. Treatment of underlying conditions, the use of multiple diagnostic techniques, and appropriate antifungals in conjunction with surgery can all contribute to infection control.

Troponin is a useful marker in clinical decision making in hospitalized patients with COVID-19 infections.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

c-Myc Inhibition Using 10058-F4 Increased the Sensitivity of Acute Promyelocytic Leukemia Cells to Arsenic Trioxide Via Blunting PI3K/NF-κB Axis.

BACKGROUNDS: Although ATO is widely used to treat acute promelocytic leukemia (APL), the appropriate effects of the drug as a single agent are achieved in high doses which are not clinically achievable without the risk of side effects; highlighting the necessity of its application in a combined-modality. Herein, we aimed to investigate whether c-Myc inhibition could reinforce the anti-leukemic effect of ATO, while reducing its concentration in APL cells. METHODS: NB4 cells were treated with the relevant concentrations of 10058-F4 (c-Myc inhibitor) and ATO, and then the survival of the cells was evaluated using trypan blue, MTT and BrdU assays. Moreover, the mechanism of action of the agents were evaluated using Flow cytometry, qRT-PCR and western blot analysis. RESULTS: We found that the inhibition of c-Myc using 10058-F4 could enhance the anti-leukemic effect of ATO in APL cells through reducing the phosphorylation of IκB, decreasing the expression of the anti-apoptotic genes and in turn, inducing a caspase-3-dependent apoptotic cell death. Moreover, the combination of 10058-F4 and ATO abrogated the activation of the PI3K pathway, while neither agent had significant suppressive impact on this pathway; suggesting for the first time that probably the companionship of c-Myc inhibitor may be an appealing strategy for shifting the resistance condition toward a chemo-sensitive phenotype, without the necessity to elevate the effective dose of ATO. CONCLUSION: Given the efficacy of 10058-F4 in adjuvanting approaches, we suggest this small molecule inhibitor as an impressing agent to be used alongside ATO in the treatment of APL.

Trend of Gastric Cancer Incidence in an Area Located in the Center of Iran: 2009-2014.

PURPOSE: There are remarkable differences between the incidence and mortality of gastric cancer in different places of the world. This study, for the first time, estimated the information around the incidence rates and trends of gastric cancer in the central area of Iran, Arak metropolitan. METHODS: In this study, all cases with gastric cancer in Arak from 2009 to 2014 were included. Direct standardized method was applied to estimate age-standardized incidence rates (ASIRs) by a STATA package, with efficient interval estimation that might be preferable in the case of rare diseases, including cancer data. The obtained standard errors were used to calculate annual percent changes (APCs) by the Joinpoint analysis. RESULTS: Annual ASIRs of gastric cancer were 23.92 (95% CI 21.62, 26.37) and 9.60 (95% CI 8.20, 11.18) for male and female, respectively. In male, APC of ASIRs was - 5.00% (95% CI - 9.32, - 0.47). In contrast, among female, it was - 2.69% (95% CI - 31.56, 38.34) that was statistically insignificant. CONCLUSIONS: The ASIRs have significantly decreased trends in males, but not in females. The preventive strategies should be a focus on the declining of the risk factors and the quick early diagnosis of gastric cancer.

The Relationship Between rs3212986C>A Polymorphism and Tumor Stage in Lung Cancer Patients.

Background The nucleotide excision repair (NER) system is one of the most important deoxyribonucleic acid (DNA) repair mechanisms and is critical for chemotherapy resistance. We conducted the present study to investigate the association between two polymorphisms of excision of repair cross-complementing group 1 (ERCC1), the key component of the NER pathway, and the clinicopathological features of patients with non-small cell lung cancer (NSCLC). Methods A total of 38 patients with confirmed NSCLC were included in our study. DNA was extracted from peripheral blood. ERCC1 rs3212986 (8092) and rs11615 (118) were genotyped using molecular assays including polymerase chain reaction (PCR) with restriction fragment length polymorphism (by MboII and HpyCH4 enzymes) and sequencing. Results The PCR results indicated the correct performance of the genomics extraction and molecular protocols. The distribution of C/C, C/A and A/A genotypes at position 8092 was 42.10%, 47.36%, and 10.52% respectively (P=0.03). Multivariate regression analysis showed that there was a significant correlation between C8092A (rs3212986) polymorphism and metastasis, grade of the tumor, and response to treatment. Individuals carrying the rs3212986 CA genotype and A allele had a significantly worse response to the treatment. Also, the correlation between alteration at this genomics location and patients with NSCLC who used to smoke cigarettes was positive. However, no significant association was detected between rs11615 C118>T polymorphism and demographic characteristics of patients with NSCLC. Conclusion We concluded that in lung cancer patients there is a relationship between tumor stage and rs3212986C>A polymorphism.

Evaluation of Splicing on X-box Binding Protein Transcript in Tissue Samples of Colorectal Cancer.

Background The genetic etiology of colorectal cancer (CRC) is the occurrence of mutation in the genes involved in signal transduction pathways including that of cellular responses to endoplasmic reticulum (ER) stress. This study examines alterations of pre-messenger ribonucleic acid (pre-mRNA) splicing in X-box binding protein (XBP) transcripts related to the ER stress pathway in CRC. Materials and methods In this study, samples were deparaffinized and underwent RNA extraction. A total of 30 synthesized complementary deoxyribonucleic acid (cDNA) templates from the extracted RNAs related to tumor and non-tumor CRC samples, collected over three years and containing pathological data, were subjected to semi-quantitative reverse transcriptase polymerase chain reaction (sqRT-PCR). These cDNA templates were amplified in reaction tubes with specific primers for both spliced and non-spliced isoforms of XBP. Results with P< .05 were considered statistically significant. Results Microscopic assessment represented lymphocyte-rich effusion in tumor samples. sqRT-PCR electrophoresis results showed spliced and non-spliced forms of XBP messenger RNA in the studied samples. In addition, our data showed there were more than 7.8 times the total number of spliced variants in the marginal tumor samples than in the tumor tissue samples (P<.05). Conclusion Alterations of expression in genes involved in stress signaling pathways in cancer have been identified previously. Our results showed an inverse relationship between XBP splicing and CRC tumor tissue, possibly lead to the inactivation of apoptosis in the downstream response to ER stress. However, we propose that the remaining genes in this pathway should undergo gene expression analysis using a greater number of samples.

Comparison of the Effects of Omega 3 and Vitamin E on Palcitaxel-Induced Peripheral Neuropathy.

BACKGROUND: Paclitaxel-induced peripheral neuropathy is the most important side effect limiting the use of this medication. AIM: This study aimed to compare the effects of omega-3 and vitamin E on the incidence of peripheral neuropathy in patients receiving Taxol. METHODS: In this clinical trial, 63 patients who were a candidate for receiving taxol, were enrolled based on inclusion and exclusion criteria. In group O, patients received 640 mg omega-3 three times a day, and group E, received 300 mg vitamin E two times a day. Patients took the supplements up to three months after the onset of Taxol. Group P received placebo for a similar period. All patients referred to a neurologist for electrophysiological evaluation before the onset of chemotherapy and at months 1 and 3. The presence of neuropathy and its progression was recorded by the neurologist. RESULTS: Neurological examination in this study indicated that 6 patients (28.6%) in Group O, 7 patients (33.3%) in group E, and 15 patients (71.4%) in placebo group started peripheral neuropathy. There was a significant difference between intervention groups and the placebo group (p = 0.0001) and no significant difference between intervention groups (p = 0.751). CONCLUSION: Our data suggested that vitamin E and omega-3 may significantly reduce the incidence of Paclitaxel-induced peripheral neuropathy. Routine administration of such supplements that have no special side effect for patients under chemotherapy may greatly enhance their quality of life.

Association of rs1042522 SNP with Clinicopathologic Factors of Breast Cancer Patients in the Markazi Province of Iran.

BACKGROUND: The nucleotide changes in different genetic loci increased the incidence risk of breast cancer. AIM: The aim of present study was to investigate genotype distribution at codon 72 of the TP53 gene (rs1042522) in breast cancer patients to achieve a potential diagnostic marker related to some demographic feathers. METHODS: In our case-control study, blood samples were collected from a total of 34 patients harboured breast cancer. DNA was extracted, and nested-PCR was performed. Products were digested with AccII and subsequently were sequenced. Results were compared with samples characteristics. RESULTS: The PCR results indicated the correct implementation of extraction and amplification protocol. The genotypic distribution at codon 72 of TP53 in control group was 20%, 62.4% and 16.6% for Arg (wildtype), Arg/Pro (heterozygous) and Pro (homozygous variant) respectively. Also, this distribution in the patient group was 23.52% homozygous, 50% heterozygous, and 26.47% another homozygous variant (Adjusted odds ratio: 1.12 and 95%CI = 0.57 to 2.2, P = 0.03). The absence of Arg at codon 72 of TP53 is relevant with age higher than 40 years and metastasis to other organs. CONCLUSION: Polymorphism at codon 72 of TP53 was associated with high-grades of breast cancer risk and different responses to chemotherapy treatment. It is recommended genotype distribution of codon 72 of TP53 before chemotherapy.