Different Isoforms of PML-RARA Chimeric Protein in Patients with Acute Promyelocytic Leukemia: Survival Analysis per Demographic Characteristics, Clinicohematological Parameters, and Cytogenetic Findings.

Background & Objective: Acute Promyelocytic Leukemia (APL) is a medical emergency with potentially fatal complications. APL primarily results from a chromosomal translocation (t(15;17)(q22;q21)), leading to the formation of the PML-RARA fusion gene with three possible isoforms. This study aims to investigate the characteristics of Iranian APL patients, the distribution of PML-RARA isoforms, and survival analysis. Methods: We included 145 consecutive eligible patients in this study. Data were collected through archived documents and phone inquiries, following consent. Subsequently, we analyzed the data using SPSS software version 26.0. Results: We examined 75 men and 70 women, with a mean age of 34 years (range: 2-78 years). Besides t(15;17) (q22;q21), 45.6% had other chromosomal abnormalities. The prevalence of bcr1 and bcr3 isoforms was 73% and 27%, respectively. bcr3 correlated with higher white blood cell (WBC) counts, additional chromosomal abnormalities, and faster Complete Hematologic Response (CHR). Early death occurred in approximately 36% of all patients. The mean overall survival time was 73.5 months, with 120-month survival rates of 53.8% for all patients and 83.9% for those who achieved CHR. Univariate analysis identified old age, relapse, lower platelet (PLT) counts, higher WBC counts, and leukocytosis as survival risk factors. However, in multivariate analysis, only old age and higher WBC counts were identified as adverse prognostic factors. Conclusion: In Iranian APL patients, bcr1 predominates, while bcr3 correlates with higher WBC counts, high-risk categorization, additional chromosomal abnormalities, and faster CHR. Survival is negatively impacted by old age, relapse, lower PLT counts, higher WBC counts, and leukocytosis.

The molecular characteristics of colorectal cancer: Impact of Ibuprofen and hyperthermia.

Despite various treatment options available for colorectal cancer, the survival rates for patients remain low. This study investigated the effects of hyperthermia and Ibuprofen on human colorectal adenocarcinoma cells (HT-29) viability, proliferation, and gene expression related to tumor suppression, Wnt signaling pathways, proliferation, and apoptosis The cells were exposed to hyperthermia at 42 or 43°C for 3 hours or Ibuprofen at different concentrations (700-1500 µM), and the effects were analyzed through MTT assay, trypan blue staining, and quantitative Real-time PCR. The study used quantitative Real-time PCR (qRT-PCR) to evaluate the effect of hyperthermia and Ibuprofen on the expression of various genes associated with tumor suppression, proliferation, Wnt signaling pathway, and apoptosis. The results revealed that hyperthermia caused a minor reduction in the viability and proliferation of HT-29 cells, but the decrease was not statistically significant (P<0.05). On the other hand, Ibuprofen caused a concentration-dependent decrease in the viability and proliferation of HT-29 cells. Both hyperthermia and Ibuprofen reduced the expression of WNT1, CTNNB1, BCL2, and PCNA genes, and increased the expression of KLF4, P53, and BAX genes. However, the changes in gene expression were not statistically significant in cells treated with hyperthermia. The findings suggest that Ibuprofen is more effective in reducing cancer cell proliferation by promoting apoptosis and inhibiting the Wnt signaling pathway than hyperthermia, which had some impact but was not statistically significant. The study highlights the potential of Ibuprofen as a targeted therapy for colorectal cancer.

Expression Levels of Il-6 and Il-18 in Acute Myeloid Leukemia and Its Relation with Response to Therapy and Acute GvHD After Bone Marrow Transplantation.

Cytokines seem to play a crucial role in physiological and pathological conditions of acute myeloid leukemia (AML). The aim of this study was to evaluate the expression levels of interleukins-6 (IL-6) and IL-18 in patients with AML and its correlation with response to therapy and graft versus host disease (GvHD) after bone marrow transplantation. The expression levels of IL-6 and IL-18 genes were done in all patients and compared with matched control. Complete remission (CR) was used for evaluation of the effects of these cytokines on response to treatment in patients group. The expression level of these cytokines was also evaluated in patients who underwent bone marrow transplantation and experienced acute GvHD in compare with patients without aGvHD. Il-6 gene expression level was significantly higher in these patients in comparison with control but Il-18 gene expression level was not statistically significant compared to control group. Il-6 and also Il-18 expression levels were significantly higher in patients without a response to treatment according to CR compared to patient's whit response to treatment as well as patients experienced aGvHD after bone marrow transplantation. IL-6 and Il-18 are important markers in the progression of the disease and could be considered as a prognostic marker in acute leukemia. It is recommended that more studies with larger study groups and more involved cytokines are needed for more evaluation of the cytokine roles in pathophysiology and progression of acute leukemia.

Detection of Human Papillomavirus in Papillary Thyroid Carcinoma and its Association with Tumor Staging and Pathologic Features.

Background: The role of human papillomavirus (HPV), as a common infection, has been evaluated in many cancers such as the cervix and squamous cell carcinoma of the head and neck. To the best of our knowledge, for the first time, the association of HPV with papillary thyroid carcinoma (PTC) and its pathologic features are investigated. Methods: A retrospective cross-sectional study was conducted from May 2014 to January 2018 in several hospitals affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. Thyroid tissue specimens of patients diagnosed with PTC (n=82) and benign thyroid nodules (n=77) were collected using the consecutive sampling method. The presence of HPV in PTC, adjacent normal tissue, and benign thyroid nodules was evaluated using the polymerase chain reaction (PCR) method. The frequency of HPV positivity in PTC tissues was compared with benign thyroid nodules and adjacent normal tissue. Association of pathologic features of PTC with HPV positivity was also investigated. Data were analyzed using SPSS version 21.0, and P values less than 0.05 were considered statistically significant. Results: HPV PCR positivity was observed in 3.8% of benign thyroid nodules and 13.4% of PTC samples but in none of the adjacent normal tissues. After adjustment for age and sex, the prevalence of HPV PCR positivity in the PTC tissues was significantly more than the benign thyroid nodules (P=0.015). The prevalence was also significantly higher than the adjacent normal tissues (P<0.001). Conclusion: There was a significant association between PTC and HPV positivity. Further studies are required to determine the cause and effect of the association between these two conditions.

Prevalence of Human Papilloma Virus in Sinonasal Papilloma in Southern Iranian Population.

STATEMENT OF THE PROBLEM: Sinonasal papilloma (SNP) is a rare benign lesion characterized by high recurrence rate and malignant transformation. PURPOSE: This study aimed to investigate the prevalence of human papilloma virus (HPV) infection in these lesions in South of Iran. MATERIALS AND METHOD: In this cross sectional retrospective study, a total of 41 patients, 38 SNP and 3 SNP/Squamous cell carcinoma cases, from 2007 to 2014 were studied. Human papilloma virus (HPV) DNA detection was performed by nested PCR method and positive cases were analyzed for high risk HPV-16 and HPV-18. RESULTS: HPV was detected in 31.7%; HPV- 16 in 4.9% and HPV 18 was not detected at all. Dysplastic epithelium was detected in 53% that was not associated with HPV. Three cases were accompanied with malignant transformation that HPV genome was detected in only one case and none of them were positive for HPV16 /18 genomic DNA. CONCLUSION: Current research suggests that HPV may be involved in the development of SNP. But the high risk HPV is not important in malignant transformation. More studies are needed to elucidate the possible etiologic mechanism between HPV, inverted papilloma, and squamous cell carcinoma.

FMS-Like Tyrosine Kinase 3 (FLT3) and Nucleophosmin 1 (NPM1) in Iranian Adult Acute Myeloid Leukemia Patients with Normal Karyotypes: Mutation Status and Clinical and Laboratory Characteristics.

OBJECTIVE: In this study, we evaluated the frequency of FMS-like tyrosine kinase 3 (FLT3-ITD and FLT3-TKD) and nucleophosmin (NPM1) mutations in Iranian patients with cytogenetically normal acute myeloid leukemia (CN-AML). The clinical and laboratory characteristics were compared between wild-type and mutant cases. MATERIALS AND METHODS: Seventy newly diagnosed de novo AML patients were recruited at the time of diagnosis prior to chemotherapy; among them, 54 had CN-AML. For detecting mutations, the FLT3 and NPM1 genes were amplified by the polymerase chain reaction method, followed by direct sequencing. RESULTS: Our results showed that the frequencies of FLT3-ITD, FLT3-TKD, and NPM1 mutations in CN-AML patients were 25.9%, 5.9%, and 20.8%, respectively. The most frequent NPM1 mutation type was the type A mutation. The FLT3-ITD mutation was seen more frequently in non-M3 patients compared with M3 patients. No mutation was observed in either the FLT3-TKD or the NPM1 gene in patients in the M3 French-American-British group. There was no significant association between the presence of FLT3-ITD and NPM1 mutations in CN-AML patients (p>0.05). The frequency of FLT3-ITD, FLT3-TKD, and NPM1 mutation was higher in CN-AML patients in comparison with AML patients with cytogenetic aberrations, although the differences were not statistically significant (p>0.05). There were no significant differences in mean white blood cell and platelet counts, serum hemoglobin levels, and bone marrow blast percentages between patients with wild-type and mutant FLT3-ITD and NPM1 genes (p>0.05). No difference was observed in the frequency of FLT3-ITD or NPM1 mutation regarding age or sex (p>0.05). CONCLUSION: Given the high stability of NPM1 during the disease course, it can be used in combination with FLT3 as well as other known genetic markers to monitor patients, especially for minimal residual disease detection.

Interleukin-23 Receptor Gene Variants in Acute Lymphoblastic Leukemia and Their Relation to Prognostic Factors.

BACKGROUND: Interleukin (IL)-23 has an important role in tumor immune regulation. OBJECTIVE: To investigate the possible association of interleukin-23 receptor (IL23R) gene variants rs1884444, rs10889677 and rs11209026 with development of acute lymphoblastic leukemia (ALL). METHODS: The IL23R variants were studied in 164 ALL patients and compared to 175 healthy controls by polymerase chain reaction-restriction fragment length polymorphism. The relationship between these variants and clinical and laboratory features of the patients and response to therapy were evaluated. RESULTS: No significant differences in genotype and allele frequencies existed between patients and controls. The rs1884444TG genotype was significantly lower in patients who relapsed (24.2%) compared to those without relapse (55.9%, p=0.006). Fewer patients who relapsed had evidence of the G allele (p=0.034). The TG genotype was associated with a longer complete remission at 1804±116 days compared to other genotypes (<1217 days, p=0.028), however, this result was not significant in multivariate analysis. The rs10889677 AA genotype and A allele were associated with age (p<0.041) and platelet number (p=0.03) in precursor-B cell ALL (B-ALL) patients. Both occurred more frequently in patients aged 2-10 years (63.6% and 66%, respectively) and in those with platelets >100×10ˆ3 µL (68.4% and 52.4%, respectively). CONCLUSION: Our findings showed a lack of association of the studied polymorphisms with the risk of ALL. The influence of the rs1884444 polymorphism on relapse rate and association of rs10889677 AA genotype with favorable prognostic factors suggest the effect of the studied polymorphisms on ALL response to therapy and prognosis.

The Prevalence of Human Papilloma Virus in Squamous Cell Carcinoma of Oral Tongue.

BACKGROUND AND OBJECTIVE: Oral tongue Squamous Cell carcinoma (SCC) commonly involves males between the sixth to eighth decades of life. Major risk factors are tobacco usage and alcohol consumption. The increasing number of patients developing oral tongue cancer without these well-known risk factors suggests that a viral infection, such as Human Papillomavirus (HPV), may be responsible for this increase, by acting as an oncogenic agent. This study investigated the prevalence of HPV infection and its clinicopathologic significance in oral tongue SCCs. METHODS: Tissue blocks from a total of 50 cases (patients with oral tongue SCC) and 50 controls (palatine tonsillar tissues with benign diagnosis) were selected. DNA was extracted from tumoral and non-tumoral tissue blocks. Detection of common HPV DNA by nested Polymerase Chain Reaction (PCR), and high-risk genotypes, HPV 16 and HPV 18, by conventional PCR, was achieved and the results correlated with clinicopathological parameters. RESULTS: Of the 50 patients (18 males and 32 females with a mean age of 57.36±12.18 years, and age range of 27 to 86 years), 7 (14%) had HPV positive results. None of the control group subjects had HPV DNA positive results (P-value of 0.012). The HPV genotype 16/18 was not detected in positive cases. No statistically significant association was found between HPV status and gender, age, tumor grade, tumor stage or lymph node involvement. CONCLUSION: Although there was a significantly higher prevalence of HPV in oral tongue SCC, its association with carcinogenesis in this area requires further studies.

Dicer Gene Expression as a Prognostic Factor in Acute Lymphoblastic Leukemia and Chronic Lymphocytic Leukemia in Fars Province.

Alterations in the expression of microRNAs (miRNAs) have been proposed to play a role in the pathogenesis of acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL). Dicer is one of the main regulators of miRNA biogenesis, and deregulation of its expression has been indicated as a possible cause of miRNA alterations observed in various cancers. Our aim was to analyze the expression of the Dicer protein and its relationship with ALL and CLL. This cross-sectional study was performed from 2010 to 2012 in Shahid Faghihi Hospital, Shiraz, Iran. In this study, 30 patients with CLL, 21 patients with ALL, 10 child healthy donors, and 19 adult healthy donors were recruited. The patients' samples were checked via flow cytometry, immunohistochemistry, and immunocytochemistry. The controls' samples were also examined in the hematology ward. Total RNA was extracted from the bone marrow and peripheral blood samples of the patients and controls. Then, reverse-transcription polymerase chain reaction was used to estimate the level of Dicer miRNA. The outcomes of the expression analysis of Dicer revealed statistically significant differences between the ALL patients/child healthy controls (mean±SD, 0.19±0.28 vs. 0.73±0.12; P<0.001) and the CLL patients/adult healthy controls (mean±SD, 0.24±0.25 vs. 0.41±0.28; P=0.033). This is the first piece of evidence showing that the expression of the Dicer gene greatly decreased in the patients with ALL in comparison to the child controls. The expression of the Dicer gene was also downregulated in the patients with CLL compared to the adult controls. Given the above findings, the expression of Dicer may play an important role in the progression and prognosis of these diseases.

Effect of iron on expression of efflux pump (adeABC) and quorum sensing (luxI, luxR) genes in clinical isolates of Acinetobacter baumannii.

Resistance-nodulation-division efflux system (RND) adeABC contributes to intrinsic resistance to various drug classes in Acinetobacter baumannii. Similarly, quorum sensing (QS) plays an important role in the biofilm formation and pathogenicity of this bacterium. The aims of this study were to evaluate the influence of iron limitation on the expression of efflux pump (adeABC) genes and QS (luxI, luxR) system by relative quantitative real-time polymerase chain reaction (qRT-PCR). In addition, DNA sequence and phylogenetic relatedness of biofilm-associated protein (Bap) gene was also investigated. Sixty-five multidrug-resistant isolates of A. baumannii were recovered from ICU patients of three hospitals in Kerman, Iran. The isolates were highly resistant to at least 11 antibiotics (MIC ≥64 µg/mL); however, 87% and 89% were susceptible to colistin and tigecycline, respectively (MIC 0.05 µg/mL) (p ≤ 0.05). We detected the presence of RND efflux pump, QS, and bap genes with the frequencies of 92% (adeA), 61.5% (adeB), 84.6% (adeC), 80% (luxI), 61% (luxR), and 66% (bap), respectively. qRT-PCR analysis showed that in some isolates, expression of both adeABC and luxI/R was increased more than fourfold in the presence of low iron (20 µm), suggesting the additional regulatory role of iron on both efflux pump and QS system. Alignment and phylogenetic analysis on the strong biofilm forming isolates confirmed that the fragments amplified were indeed part of bap gene and deduced sequence was similar to A. baumannii K9B410.

Fas gene variants in childhood acute lymphoblastic leukemia and association with prognosis.

Fas molecule is one of the main important molecules involved in apoptotic cell death. Single nucleotide polymorphisms in the promoter of Fas gene at positions -1377G/A and -670 A/G may affect its expression and play an important role in the pathology of leukemia. In the present study the association between these polymorphisms and risk of the development of acute lymphoblastic leukemia (ALL) in children with ALL compared to cancer-free control subjects was examined by polymerase chain reaction- based restriction fragment length polymorphism. The relationship between the polymorphisms and clinical and laboratory features of the patients and response to therapy were determined. No significant differences in genotype and allele frequencies between the patients and the control subjects at positions -670 and -1377 were detected. Evaluation of the prognostic factors revealed an association between the GG genotype at position -670 and liver involvement in ALL patients (p < 0.04). Although patients with -1377 AA genotype showed shorter mean complete remission duration, the result of survival analysis did not reach to be significant. In conclusion, results of this study showed no contribution of Fas genotypes at positions -670 and -1377 to risk of ALL in children. The association of Fas GG genotype at position -670 with liver involvement in the patients may show its important role in prognosis of ALL.

Prevalence of high-risk human papillomavirus types 16 and 18 in healthy women with cytologically negative pap smear in Iran.

BACKGROUND: Because human papillomavirus (HPV) is one of the causal factors in cervical cancer, understanding the epidemiology of this infection is an important step towards developing strategies for prevention. MATERIALS AND METHODS: We evaluated the prevalence of high-risk human papillomavirus Types 16 and 18 in cervical samples from 402 healthy women with normal Pap smears by testing with type-specific primers in the polymerase chain reaction. Participants were seen at two gynecological clinics affiliated to the Shiraz University of Medical Sciences in Iran. RESULT: The prevalence of positive HPV findings was 5.5%; high-risk HPV human papillomavirus Type 16 prevalence was 2% and no patient harbored HPV-18. The prevalence of HPV was 4.5% in younger age group and gradually increased to 20% in the 4 th decade. CONCLUSION: The prevalence of high-risk HPV was highest in the youngest women and gradually decreased with age. Overall, the prevalence of HPV in our population is low.

Molecular diagnosis of nasopharyngeal carcinoma using detection of Epstein-Barr virus latent membrane protein-1 gene in cervical metastatic lymph nodes.

BACKGROUND: Cervical lymphadenopathy could be a manifestation of occult nasopharyngeal carcinoma (NPC). Epstein-Barr virus (EBV) is frequently detected in NPC, and its malignant transformation is associated through the action of the oncoprotein latent membrane protein-1 (LMP-1). PURPOSE: The aim of this study was to investigate whether a primary nasopharyngeal origin could be localized by detection of EBV LMP-1 gene in cervical metastatic lymph nodes. MATERIALS AND METHODS: In this prospective study, 32 paraffin-embedded tissues of various head and neck carcinomas and 20 normal tonsil specimens were examined for the presence of LMP-1 gene, using polymerase chain reaction. RESULTS: Ten of 12 nasopharyngeal biopsies and 8 of 10 metastatic lymph nodes of the same NPC were positive for LMP-1 gene. The LMP-1 gene was detected in metastatic lymph nodes of NPC, with a sensitivity of 80%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 91%. On the contrary, the LMP-1 gene was not detected in any of the samples of other head and neck carcinomas and their metastatic nodes as well as in tonsillar specimens. There was a significant association between the presence of LMP-1 gene and tumor location in the nasopharynx (P < .0001). CONCLUSION: The presence of LMP-1 gene in metastatic cervical lymph nodes is significantly associated with nasopharyngeal origin of the carcinoma. Meanwhile, EBV has no role in the tumorigenesis of carcinomas arising from other head and neck regions.