Pub Date : 2024-04-21DOI: 10.18502/ijhoscr.v18i2.15371
Mohammad Soltani, Mohammad Jafar Sharifi, Parvin Khalilian, Mehran Sharifi, Pardis Nematollahi, Hooriyeh Shapourian, M. Hakemi
Background: Myelodysplastic syndromes (MDS) are determined by ineffective hematopoiesis and bone marrow cytological dysplasia with somatic gene mutations and chromosomal abnormalities. Accumulating evidence has revealed the pivotal role of NLRP3 inflammasome activation and pyroptotic cell death in the pathogenesis of MDS. Although MDS can be diagnosed with a variety of morphologic and cytogenetic tests, most of these tests have limitations or problems in practice. Materials and Methods: In the present study, we evaluated the expression of genes that form the inflammasome (NLRP3, ASC, and CASP1) in bone marrow specimens of MDS patients and compared the results with those of other leukemias to evaluate their diagnostic value for MDS. Primary samples of this observational cohort study were collected from aspiration samples of patients with myelodysplastic syndromes (27 cases) and patients with non-myelodysplastic syndrome hematological cancers (45 cases). After RNA extraction and c.DNA synthesis, candidate transcripts and housekeeping transcripts were measured by real-time PCR method (SYBER Green assay). Using Kruskal-Wallis the relative gene expressions were compared and differences with p value less than 0.05 were considered as significant. Discrimination capability, cut-off, and area under curve (AUC) of all markers were analyzed with recessive operation curve (ROC) analysis. Results: We found that Caspase-1 and ASC genes expressed at more levels in MDS specimens compared to non-MDS hematological malignancies. A relative average expression of 10.22 with a p-value of 0.001 and 1.86 with p=0.019 was detected for Caspase-1 and ASC, respectively. ROC curve analysis shows an AUC of 0.739 with p=0.0001 for Caspase-1 and an AUC of 0.665 with p=0.0139 for ASC to MDS discrimination. Conclusion: Our results show that Caspase-1 and ASC gene expression levels can be used as potential biomarkers for MDS diagnosis. Prospective studies with large sample numbers are suggested.
{"title":"Potential Diagnostic Value of Abnormal Pyroptosis Genes Expression in Myelodysplastic Syndromes (MDS): A Primary Observational Cohort Study","authors":"Mohammad Soltani, Mohammad Jafar Sharifi, Parvin Khalilian, Mehran Sharifi, Pardis Nematollahi, Hooriyeh Shapourian, M. Hakemi","doi":"10.18502/ijhoscr.v18i2.15371","DOIUrl":"https://doi.org/10.18502/ijhoscr.v18i2.15371","url":null,"abstract":"Background: Myelodysplastic syndromes (MDS) are determined by ineffective hematopoiesis and bone marrow cytological dysplasia with somatic gene mutations and chromosomal abnormalities. Accumulating evidence has revealed the pivotal role of NLRP3 inflammasome activation and pyroptotic cell death in the pathogenesis of MDS. Although MDS can be diagnosed with a variety of morphologic and cytogenetic tests, most of these tests have limitations or problems in practice. \u0000Materials and Methods: In the present study, we evaluated the expression of genes that form the inflammasome (NLRP3, ASC, and CASP1) in bone marrow specimens of MDS patients and compared the results with those of other leukemias to evaluate their diagnostic value for MDS. \u0000Primary samples of this observational cohort study were collected from aspiration samples of patients with myelodysplastic syndromes (27 cases) and patients with non-myelodysplastic syndrome hematological cancers (45 cases). After RNA extraction and c.DNA synthesis, candidate transcripts and housekeeping transcripts were measured by real-time PCR method (SYBER Green assay). Using Kruskal-Wallis the relative gene expressions were compared and differences with p value less than 0.05 were considered as significant. Discrimination capability, cut-off, and area under curve (AUC) of all markers were analyzed with recessive operation curve (ROC) analysis. \u0000Results: We found that Caspase-1 and ASC genes expressed at more levels in MDS specimens compared to non-MDS hematological malignancies. A relative average expression of 10.22 with a p-value of 0.001 and 1.86 with p=0.019 was detected for Caspase-1 and ASC, respectively. ROC curve analysis shows an AUC of 0.739 with p=0.0001 for Caspase-1 and an AUC of 0.665 with p=0.0139 for ASC to MDS discrimination. \u0000Conclusion: Our results show that Caspase-1 and ASC gene expression levels can be used as potential biomarkers for MDS diagnosis. Prospective studies with large sample numbers are suggested. \u0000 ","PeriodicalId":94048,"journal":{"name":"International journal of hematology-oncology and stem cell research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140678665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-21DOI: 10.18502/ijhoscr.v18i2.15368
Zahra Kashani Khatib, Asma Maleki, A. Pourfatollah, A. Hamidieh, Shirin Ferdowsi
Background: Cancer is among the serious health problems of the medical world, for treatment of which severe treatments are used. However, the prognosis of cancer patients is still poor. The application of NK cell-derived exosomes (NK-Exo) is a new method for cancer immunotherapy. These nanoparticles with a size range of 30-120 nm are a small model of mother cells. In this study, the anti-tumor activity of NK-Exo and LAK-Exo (activated NK cell-derived exosome) against acute myeloid leukemia (AML) is investigated in vitro. Materials and Methods: The MACS method was performed for the separation of NK cells from the buffy coats of healthy donors, and an EXOCIBE kit was used for the isolation of NK-Exo. After treating the KG-1 cell line with different doses of NK-Exo, MTT assay, and annexin V-PE were done to evaluate cell proliferation and apoptosis, respectively, and for confirmation of involved proteins, Real-Time PCR and western blotting were performed. Results: Anti-tumor activity of NK-Exo and LAK-Exo was dose- and time-dependent. Their highest activities were observed following 48 hours of incubation with 50 µg/ml exosome (p<0.0001). However, this cytotoxic activity was also seen over a short period of time with low concentrations of NK-Exo (p<0.05) and LAK-Exo (p<0.001).The cytotoxic effect of LAK-Exo on target cells was significantly higher than NK-EXO. The induction of apoptosis by different pathways was time-point dependent. Total apoptosis was 34.56% and 51.6% after 48 hours of tumor cell coculture with 50µg/ml NK-Exo and LAK-Exo, respectively. Significant expression of CASPASE3, P38, and CYTOCHROME C genes was observed in the cells treated with 50 µg/ml NK-Exo and LAK-Exo. Conclusion: Our study confirmed the antileukemia activity of NK-Exo against AML tumor cells in vitro. Therefore, NK-Exo can be considered as a promising and effective treatment for leukemia therapy.
背景：癌症是医学界严重的健康问题之一，在治疗方面，人们采用了严厉的治疗方法。然而，癌症患者的预后仍然很差。应用 NK 细胞衍生的外泌体（NK-Exo）是癌症免疫疗法的一种新方法。这种纳米颗粒的尺寸范围为 30-120 纳米，是一种小型的母细胞模型。本研究在体外研究了NK-Exo和LAK-Exo（活化的NK细胞衍生外泌体）对急性髓性白血病（AML）的抗肿瘤活性。材料与方法：采用MACS方法从健康供体的水包衣中分离NK细胞，并使用EXOCIBE试剂盒分离NK-Exo。用不同剂量的 NK-Exo 处理 KG-1 细胞系后，分别用 MTT 检测和附件素 V-PE 评估细胞增殖和凋亡情况，并用 Real-Time PCR 和 Western 印迹法确认相关蛋白。结果NK-Exo和LAK-Exo的抗肿瘤活性呈剂量和时间依赖性。与 50 µg/ml 外泌体培养 48 小时后，它们的活性最高（p<0.0001）。然而，低浓度的NK-Exo（p<0.05）和LAK-Exo（p<0.001）也能在短时间内显示出这种细胞毒性活性。不同途径诱导细胞凋亡与时间点有关。肿瘤细胞与50µg/ml NK-Exo和LAK-Exo共培养48小时后，凋亡率分别为34.56%和51.6%。在使用 50 µg/ml NK-Exo 和 LAK-Exo 处理的细胞中观察到 CASPASE3、P38 和 CYTOCHROME C 基因的显著表达。结论我们的研究证实了 NK-Exo 在体外对 AML 肿瘤细胞的抗白血病活性。因此，NK-Exo 可被视为一种治疗白血病的有效方法。
{"title":"Antileukemia Activity of Human Natural Killer Cell-Derived Nanomagic Bullets against Acute Myeloid Leukemia (AML)","authors":"Zahra Kashani Khatib, Asma Maleki, A. Pourfatollah, A. Hamidieh, Shirin Ferdowsi","doi":"10.18502/ijhoscr.v18i2.15368","DOIUrl":"https://doi.org/10.18502/ijhoscr.v18i2.15368","url":null,"abstract":"Background: Cancer is among the serious health problems of the medical world, for treatment of which severe treatments are used. However, the prognosis of cancer patients is still poor. The application of NK cell-derived exosomes (NK-Exo) is a new method for cancer immunotherapy. These nanoparticles with a size range of 30-120 nm are a small model of mother cells. In this study, the anti-tumor activity of NK-Exo and LAK-Exo (activated NK cell-derived exosome) against acute myeloid leukemia (AML) is investigated in vitro. \u0000Materials and Methods: The MACS method was performed for the separation of NK cells from the buffy coats of healthy donors, and an EXOCIBE kit was used for the isolation of NK-Exo. After treating the KG-1 cell line with different doses of NK-Exo, MTT assay, and annexin V-PE were done to evaluate cell proliferation and apoptosis, respectively, and for confirmation of involved proteins, Real-Time PCR and western blotting were performed. \u0000Results: Anti-tumor activity of NK-Exo and LAK-Exo was dose- and time-dependent. Their highest activities were observed following 48 hours of incubation with 50 µg/ml exosome (p<0.0001). However, this cytotoxic activity was also seen over a short period of time with low concentrations of NK-Exo (p<0.05) and LAK-Exo (p<0.001).The cytotoxic effect of LAK-Exo on target cells was significantly higher than NK-EXO. The induction of apoptosis by different pathways was time-point dependent. Total apoptosis was 34.56% and 51.6% after 48 hours of tumor cell coculture with 50µg/ml NK-Exo and LAK-Exo, respectively. Significant expression of CASPASE3, P38, and CYTOCHROME C genes was observed in the cells treated with 50 µg/ml NK-Exo and LAK-Exo. \u0000Conclusion: Our study confirmed the antileukemia activity of NK-Exo against AML tumor cells in vitro. Therefore, NK-Exo can be considered as a promising and effective treatment for leukemia therapy.","PeriodicalId":94048,"journal":{"name":"International journal of hematology-oncology and stem cell research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140678749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-21DOI: 10.18502/ijhoscr.v18i2.15372
Zohreh Ehsani, E. Salehifar, Emran Habibi, Reza Alizadeh-Navaei, Mahmoud Moosazadeh, Nasim Tabrizi, E. Zaboli, Versa Omrani-Nava, R. Shekarriz
Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant cancer treatment side effect that can influence both quality of life and treatment course. Melissa Officinalis (MO), due to its high content of flavonoids, has antioxidant, anti-inflammatory, and neuroprotective properties. Materials and Methods: The cancer patients diagnosed with CIPN attended a referral center in Sari (Iran). The hydroalcoholic extract of MO leaves was extracted by the maceration method. The control group received a placebo along with gabapentin as the standard treatment, and the intervention group received 500 mg Melissa officinalis 2 times daily for 3 months plus gabapentin. Patients were evaluated at the baseline and 3 months later, according to Common Terminology Criteria for Adverse Effects (CTCAE) and EORTC QLQ-C30 (Integrated System for Quality of Life Assessment). Results: A total of 40 patients were considered as group D (intervention group), and 35 patients completed the study. Out of 40 subjects in the placebo group (P), 3 patients could not tolerate the drug due to gastrointestinal disturbances. The final values of CTCAE showed a statistically significant difference (p=0.010). Indicators related to the quality of life in both groups showed a significant improvement. In the intervention group, the pain perception and diarrhea experience were significantly reduced. Conclusion: Quality of life indicators were improved by prescribing gabapentin with and without Melissa officinalis. The addition of Melissa officinalis to the chemotherapy regimen may improve diarrhea and pain perception.
{"title":"Effect of Melissa officinalis on Chemotherapy-Induced Peripheral Neuropathy in Cancer Patients: A Randomized Trial","authors":"Zohreh Ehsani, E. Salehifar, Emran Habibi, Reza Alizadeh-Navaei, Mahmoud Moosazadeh, Nasim Tabrizi, E. Zaboli, Versa Omrani-Nava, R. Shekarriz","doi":"10.18502/ijhoscr.v18i2.15372","DOIUrl":"https://doi.org/10.18502/ijhoscr.v18i2.15372","url":null,"abstract":"Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant cancer treatment side effect that can influence both quality of life and treatment course. Melissa Officinalis (MO), due to its high content of flavonoids, has antioxidant, anti-inflammatory, and neuroprotective properties. \u0000Materials and Methods: The cancer patients diagnosed with CIPN attended a referral center in Sari (Iran). The hydroalcoholic extract of MO leaves was extracted by the maceration method. The control group received a placebo along with gabapentin as the standard treatment, and the intervention group received 500 mg Melissa officinalis 2 times daily for 3 months plus gabapentin. Patients were evaluated at the baseline and 3 months later, according to Common Terminology Criteria for Adverse Effects (CTCAE) and EORTC QLQ-C30 (Integrated System for Quality of Life Assessment). \u0000Results: A total of 40 patients were considered as group D (intervention group), and 35 patients completed the study. Out of 40 subjects in the placebo group (P), 3 patients could not tolerate the drug due to gastrointestinal disturbances. The final values of CTCAE showed a statistically significant difference (p=0.010). Indicators related to the quality of life in both groups showed a significant improvement. In the intervention group, the pain perception and diarrhea experience were significantly reduced. \u0000Conclusion: Quality of life indicators were improved by prescribing gabapentin with and without Melissa officinalis. The addition of Melissa officinalis to the chemotherapy regimen may improve diarrhea and pain perception. ","PeriodicalId":94048,"journal":{"name":"International journal of hematology-oncology and stem cell research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140678944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01DOI: 10.18502/ijhoscr.v18i2.15377
Giovanna Barbosa Correia Riello, Priscila Mendonça da Silva, Francisca Andrea da Silva Oliveira, Roberta Taiane Germano de Oliveira, Francisco Eliclecio Rodrigues da Silva, Ivo Gabriel da Frota França, Vânia Maria Maciel Melo, Fábio Miyajima, Ronald Feitosa Pinheiro, Macedo Danielle S
The myelodysplastic syndrome (MDS) is a heterogeneous group of clonal disorders of hematopoietic progenitor cells related to ineffective hematopoiesis and an increased risk of transformation to acute myelogenous leukemia. MDS is divided into categories, namely lineage dysplasia (MDS-SLD), MDS with ring sideroblasts (MDS-RS), MDS with multilineage dysplasia (MDS-MLD), MDS with excess blasts (MDS-EB). The International Prognostic Classification System (IPSS) ranks the patients as very low, low, intermediate, high, and very high based on disease evolution and survival rates. Evidence points to toll-like receptor (TLR) abnormal signaling as an underlying mechanism of this disease, providing a link between MDS and immune dysfunction. Microbial signals, such as lipopolysaccharides from gram-negative bacteria, can activate or suppress TLRs. Therefore, we hypothesized that MDS patients present gut microbiota alterations associated with disease subtypes and prognosis. To test this hypothesis, we sequenced the 16S rRNA gene from fecal samples of 30 MDS patients and 16 healthy elderly controls. We observed a negative correlation between Prevotella spp. and Akkermansia spp. in MDS patients compared with the control group. High-risk patients presented a significant increase in the genus Prevotella spp. compared to the other risk categories. There was a significant reduction in the abundance of the genus Akkermansia spp. in high-risk patients compared with low- and intermediate-risk. There was a significant decrease in the genus Ruminococcus spp. in MDS-EB patients compared with controls. Our findings show a new association between gut dysbiosis and higher-risk MDS, with a predominance of gram-negative bacteria.
{"title":"Gut Microbiota Composition Correlates with Disease Severity in Myelodysplastic Syndrome.","authors":"Giovanna Barbosa Correia Riello, Priscila Mendonça da Silva, Francisca Andrea da Silva Oliveira, Roberta Taiane Germano de Oliveira, Francisco Eliclecio Rodrigues da Silva, Ivo Gabriel da Frota França, Vânia Maria Maciel Melo, Fábio Miyajima, Ronald Feitosa Pinheiro, Macedo Danielle S","doi":"10.18502/ijhoscr.v18i2.15377","DOIUrl":"10.18502/ijhoscr.v18i2.15377","url":null,"abstract":"<p><p>The myelodysplastic syndrome (MDS) is a heterogeneous group of clonal disorders of hematopoietic progenitor cells related to ineffective hematopoiesis and an increased risk of transformation to acute myelogenous leukemia. MDS is divided into categories, namely lineage dysplasia (MDS-SLD), MDS with ring sideroblasts (MDS-RS), MDS with multilineage dysplasia (MDS-MLD), MDS with excess blasts (MDS-EB). The International Prognostic Classification System (IPSS) ranks the patients as very low, low, intermediate, high, and very high based on disease evolution and survival rates. Evidence points to toll-like receptor (TLR) abnormal signaling as an underlying mechanism of this disease, providing a link between MDS and immune dysfunction. Microbial signals, such as lipopolysaccharides from gram-negative bacteria, can activate or suppress TLRs. Therefore, we hypothesized that MDS patients present gut microbiota alterations associated with disease subtypes and prognosis. To test this hypothesis, we sequenced the 16S rRNA gene from fecal samples of 30 MDS patients and 16 healthy elderly controls. We observed a negative correlation between <i>Prevotella</i> spp. and <i>Akkermansia</i> spp. in MDS patients compared with the control group. High-risk patients presented a significant increase in the genus <i>Prevotella</i> spp. compared to the other risk categories. There was a significant reduction in the abundance of the genus <i>Akkermansia</i> spp. in high-risk patients compared with low- and intermediate-risk. There was a significant decrease in the genus <i>Ruminococcus</i> spp. in MDS-EB patients compared with controls. Our findings show a new association between gut dysbiosis and higher-risk MDS, with a predominance of gram-negative bacteria.</p>","PeriodicalId":94048,"journal":{"name":"International journal of hematology-oncology and stem cell research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11166496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-20DOI: 10.18502/ijhoscr.v17i4.13921
Vedat Uygun, İbrahim Aliosmanoğlu, Hayriye Daloğlu, Seda Öztürkmen, Koray Yalçın, Gülsün Karasu, Akif Yeşilipek
Solid organ transplantation from the same donor is an established procedure for end-stage organ failure that developed after a previous hematopoietic stem cell transplantation (HSCT); however, it is rarely done in patients transplanted with unmanipulated haplo-HSCT. There are no pediatric reports regarding the long-term performance of organ transplantation after haplo-HSCT with post-transplant cyclophosphamide (PTCY).
A juvenile myelomonocytic leukemia patient, who underwent unmanipulated haplo-HSCT with PTCY from her mother at the age of 3 years, developed chronic liver graft versus host disease (GvHD) which was refractory to specific GvHD treatment. Liver transplantation (LT) from her mother (the donor of her haplo-HSCT) was decided as the next line of treatment.
LT was performed on day 540 post-HSCT, and the donor's left lateral segment was appropriately removed and attached to the recipient. The symptoms of GvHD completely regressed in a month. The patient died on day 121 after LT, because of a possible hepato-pulmonary syndrome.
Organ failure can develop after allo-HSCT secondary to GvHD and therefore performing HSCT from a haplo-donor may be superior to a matched unrelated donor in terms of subsequent organ transplantation for organ failure.
{"title":"Combined Haploidentical Hematopoetic Stem Cell Transplantation and Liver Transplantation in a Pediatric Patient","authors":"Vedat Uygun, İbrahim Aliosmanoğlu, Hayriye Daloğlu, Seda Öztürkmen, Koray Yalçın, Gülsün Karasu, Akif Yeşilipek","doi":"10.18502/ijhoscr.v17i4.13921","DOIUrl":"https://doi.org/10.18502/ijhoscr.v17i4.13921","url":null,"abstract":"Solid organ transplantation from the same donor is an established procedure for end-stage organ failure that developed after a previous hematopoietic stem cell transplantation (HSCT); however, it is rarely done in patients transplanted with unmanipulated haplo-HSCT. There are no pediatric reports regarding the long-term performance of organ transplantation after haplo-HSCT with post-transplant cyclophosphamide (PTCY).
 A juvenile myelomonocytic leukemia patient, who underwent unmanipulated haplo-HSCT with PTCY from her mother at the age of 3 years, developed chronic liver graft versus host disease (GvHD) which was refractory to specific GvHD treatment. Liver transplantation (LT) from her mother (the donor of her haplo-HSCT) was decided as the next line of treatment.
 LT was performed on day 540 post-HSCT, and the donor's left lateral segment was appropriately removed and attached to the recipient. The symptoms of GvHD completely regressed in a month. The patient died on day 121 after LT, because of a possible hepato-pulmonary syndrome.
 Organ failure can develop after allo-HSCT secondary to GvHD and therefore performing HSCT from a haplo-donor may be superior to a matched unrelated donor in terms of subsequent organ transplantation for organ failure.","PeriodicalId":94048,"journal":{"name":"International journal of hematology-oncology and stem cell research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135618386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: This study investigates the CCR7 chemokine receptor’s prognostic value in gastric cancer and its relationship to metastasis.
Materials and Methods: Normal and adjacent tumor cells in 70 patients with gastric cancer were evaluated for CCR7 expression using immunohistochemical staining. The prognostic values of high and low levels of expression of CCR7 were also evaluated by multivariate and univariate analyses.
Results: Analysis indicated high expression of CCR7 in 52.9% of tumor tissue. Moreover, high expression of CCR7 was significantly related to metastasis of lymph nodes (p = 0.00). In addition, high expression of CCR7 had a positive correlation to the disease stage (p = 0.00), age of ≥50 years (p = 0.019), male gender (p = 0.024), vascular involvement (p = 0.009), histology of tumor adenocarcinoma (p = 0.00), and poor tumor differentiation (p = 0.00). However, the high expression of the CCR7 marker was not related to the tumor size.
Conclusion: Based on our results, CCR7 expression in gastric cancer can be considered a clinical prognostic indicator in patients with gastric cancer.
{"title":"Cytoplasmic CCR7 (CCR7c) Immunoexpression Is Associated with Tumor Invasion in Gastric Cancer","authors":"Laleh Vahedi, Somayeh Sheidaei, Maryam Ghasemi, Kolsumeh Ebrahimi, Jamshid Yazdani Cherati","doi":"10.18502/ijhoscr.v17i4.13918","DOIUrl":"https://doi.org/10.18502/ijhoscr.v17i4.13918","url":null,"abstract":"Background: This study investigates the CCR7 chemokine receptor’s prognostic value in gastric cancer and its relationship to metastasis.
 Materials and Methods: Normal and adjacent tumor cells in 70 patients with gastric cancer were evaluated for CCR7 expression using immunohistochemical staining. The prognostic values of high and low levels of expression of CCR7 were also evaluated by multivariate and univariate analyses.
 Results: Analysis indicated high expression of CCR7 in 52.9% of tumor tissue. Moreover, high expression of CCR7 was significantly related to metastasis of lymph nodes (p = 0.00). In addition, high expression of CCR7 had a positive correlation to the disease stage (p = 0.00), age of ≥50 years (p = 0.019), male gender (p = 0.024), vascular involvement (p = 0.009), histology of tumor adenocarcinoma (p = 0.00), and poor tumor differentiation (p = 0.00). However, the high expression of the CCR7 marker was not related to the tumor size.
 Conclusion: Based on our results, CCR7 expression in gastric cancer can be considered a clinical prognostic indicator in patients with gastric cancer.","PeriodicalId":94048,"journal":{"name":"International journal of hematology-oncology and stem cell research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135618384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-20DOI: 10.18502/ijhoscr.v17i4.13917
Shiva Mosadegh Manshadi, Mohammad Reza Shams Ardekani
Background: Ziziphus jujube Mill. belongs to the Rhamnaceae family. It has been reported to have a variety of biological activities such as antitumor, antioxidant, and anti-inflammatory effects. This study investigates the antiproliferative effect of Ziziphus jujube on KG-1 and NALM-6 acute leukemia cell lines.
Materials and Methods: In this experimental study, the aqueous, ethyl acetate, and hydroalcoholic extracts of the Ziziphus jujube were prepared. Total phenolic and flavonoid components were detected because the presence of these compounds is associated with antioxidant and anticancer effects. Different concentrations of extracts were prepared, and KG-1 and NALM-6 cell lines were treated with them at 12, 24, 36, and 48 hours. Cell viability and IC50 values of the extracts were calculated using MTT assays. BD Cycle TEST PLUS DNA Kit was used for cell cycle progression analysis. Bcl2, Bax, and caspase-3 mRNA expressions were also assessed.
Results: Cell viability decreased in a concentration-dependent manner. The best efficacy belonged to the ethyl acetate extract. Investigation of cell cycle progression demonstrated that the number of G0/G1 cells enhanced and the number of G2/M cells decreased when the ethyl acetate extract was applied in its IC50 concentration. A considerable increase in Caspase-3 and Bax and a decrease in Bcl2 gene expression were detected in molecular examination.
Conclusion: According to our research, Ziziphus jujube ethyl acetate extract has antitumor properties on KG-1 and NALM-6 cell lines, possibly through induction of apoptosis and cell cycle regulation.
背景:Ziziphus枣厂。属于鼠李科。据报道，它具有多种生物活性，如抗肿瘤、抗氧化和抗炎作用。本研究探讨了红枣对急性白血病细胞KG-1和NALM-6的抑制作用。材料与方法:以红枣为原料，分别制备水提物、乙酸乙酯和水醇提物。检测总酚和类黄酮成分，因为这些化合物的存在与抗氧化和抗癌作用有关。制备不同浓度的提取物，分别于12、24、36、48 h作用于KG-1和NALM-6细胞株。采用MTT法计算提取液的细胞活力和IC50值。采用BD Cycle TEST PLUS DNA Kit进行细胞周期进程分析。同时检测Bcl2、Bax和caspase-3 mRNA的表达。
结果:细胞活力呈浓度依赖性下降。以乙酸乙酯提取物效果最佳。细胞周期进程的研究表明，当乙酸乙酯提取物在IC50浓度下作用时，G0/G1细胞数量增加，G2/M细胞数量减少。分子检查发现Caspase-3和Bax基因表达明显升高，Bcl2基因表达明显降低。
结论:酸枣乙酸乙酯提取物对KG-1和NALM-6细胞具有抗肿瘤作用，可能是通过诱导细胞凋亡和调节细胞周期来实现的。
{"title":"Antitumor Activity of Ziziphus Jujube Fruit Extracts in KG-1 and NALM-6 Acute Leukemia Cell Lines","authors":"Shiva Mosadegh Manshadi, Mohammad Reza Shams Ardekani","doi":"10.18502/ijhoscr.v17i4.13917","DOIUrl":"https://doi.org/10.18502/ijhoscr.v17i4.13917","url":null,"abstract":"Background: Ziziphus jujube Mill. belongs to the Rhamnaceae family. It has been reported to have a variety of biological activities such as antitumor, antioxidant, and anti-inflammatory effects. This study investigates the antiproliferative effect of Ziziphus jujube on KG-1 and NALM-6 acute leukemia cell lines.
 Materials and Methods: In this experimental study, the aqueous, ethyl acetate, and hydroalcoholic extracts of the Ziziphus jujube were prepared. Total phenolic and flavonoid components were detected because the presence of these compounds is associated with antioxidant and anticancer effects. Different concentrations of extracts were prepared, and KG-1 and NALM-6 cell lines were treated with them at 12, 24, 36, and 48 hours. Cell viability and IC50 values of the extracts were calculated using MTT assays. BD Cycle TEST PLUS DNA Kit was used for cell cycle progression analysis. Bcl2, Bax, and caspase-3 mRNA expressions were also assessed.
 Results: Cell viability decreased in a concentration-dependent manner. The best efficacy belonged to the ethyl acetate extract. Investigation of cell cycle progression demonstrated that the number of G0/G1 cells enhanced and the number of G2/M cells decreased when the ethyl acetate extract was applied in its IC50 concentration. A considerable increase in Caspase-3 and Bax and a decrease in Bcl2 gene expression were detected in molecular examination.
 Conclusion: According to our research, Ziziphus jujube ethyl acetate extract has antitumor properties on KG-1 and NALM-6 cell lines, possibly through induction of apoptosis and cell cycle regulation.","PeriodicalId":94048,"journal":{"name":"International journal of hematology-oncology and stem cell research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135618387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-20DOI: 10.18502/ijhoscr.v17i4.13922
Akram Abedi, Nasrin Namdari, Ahmad Monabati, Akbar Safaei, Parvin Rajabi, Maral Mokhtari
Myeloid sarcoma (MS) or chloroma is a localized mass composed of blastic cells of granulocytic lineage. It is a subtype of acute myeloid leukemia and usually presents as a complication of acute myeloid leukemia, myeloid dysplastic syndrome, or myeloproliferative disorder. MS occurs in 2.5-9.1% of patients with AML, precedes the clinical disease, coincidence with the onset or at relapse and in rare conditions, it can occur with no evidence of hematologic disorders. Here, we presented seven cases of MS in unusual locations or with rare presentations at presentation or relapse. We concluded that MS should be considered in the differential diagnosis of any high-grade tumor, especially in a patient with previous history of any myeloid neoplasm.
{"title":"Myeloid Sarcoma: Case Series with Unusual Locations","authors":"Akram Abedi, Nasrin Namdari, Ahmad Monabati, Akbar Safaei, Parvin Rajabi, Maral Mokhtari","doi":"10.18502/ijhoscr.v17i4.13922","DOIUrl":"https://doi.org/10.18502/ijhoscr.v17i4.13922","url":null,"abstract":"Myeloid sarcoma (MS) or chloroma is a localized mass composed of blastic cells of granulocytic lineage. It is a subtype of acute myeloid leukemia and usually presents as a complication of acute myeloid leukemia, myeloid dysplastic syndrome, or myeloproliferative disorder. MS occurs in 2.5-9.1% of patients with AML, precedes the clinical disease, coincidence with the onset or at relapse and in rare conditions, it can occur with no evidence of hematologic disorders. Here, we presented seven cases of MS in unusual locations or with rare presentations at presentation or relapse. We concluded that MS should be considered in the differential diagnosis of any high-grade tumor, especially in a patient with previous history of any myeloid neoplasm.","PeriodicalId":94048,"journal":{"name":"International journal of hematology-oncology and stem cell research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135618382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-20DOI: 10.18502/ijhoscr.v17i4.13919
Hosein Jodat, Javad Jodat, Ali Khodadadi, Abdolhassan Talaiezadeh, Nazanin Joudaki, Ali Asadirad
Background: Colorectal cancer, a solid tumor with a high prevalence, contributes significantly to annual mortality rates. Various factors, including blood groups, may influence cancer risk. Multiple studies have suggested a potential connection between ABO and Rh blood groups and colorectal cancer risk. This study aims to investigate the role of ABO and Rh blood groups as risk factors in colorectal cancer patients.
Materials and Methods: We conducted a retrospective study involving 71 colorectal cancer patients diagnosed between 2018 and 2020 in Khuzestan province, Iran, with known ABO blood types. Large-scale data from 29,922 blood donors in Khuzestan served as the healthy population control. The study analyzed the distribution of ABO blood groups among the blood donors.
Results: Our findings revealed that the distribution of blood groups among colorectal cancer patients was as follows: O (31.0%), A (29.6%), B (29.6%), and AB (9.8%). However, our analysis did not establish a significant association between colorectal cancer risk and ABO antigens (P-value = 0.636) or Rh blood group (P = 0.198). Additionally, no significant differences in ABO blood types were observed concerning gender (P = 0.802), cancer type (P = 0.338), or tumor type (P = 0.207) among colorectal cancer patients.
Conclusion: This study does not support a significant correlation between ABO and Rh blood groups and the risk of colorectal cancer, nor does it find associations with cancer type or tumor type.
{"title":"A Study of Association of ABO and Rh Blood Group with Colorectal Cancer in Khuzestan Province, Iran","authors":"Hosein Jodat, Javad Jodat, Ali Khodadadi, Abdolhassan Talaiezadeh, Nazanin Joudaki, Ali Asadirad","doi":"10.18502/ijhoscr.v17i4.13919","DOIUrl":"https://doi.org/10.18502/ijhoscr.v17i4.13919","url":null,"abstract":"Background: Colorectal cancer, a solid tumor with a high prevalence, contributes significantly to annual mortality rates. Various factors, including blood groups, may influence cancer risk. Multiple studies have suggested a potential connection between ABO and Rh blood groups and colorectal cancer risk. This study aims to investigate the role of ABO and Rh blood groups as risk factors in colorectal cancer patients.
 Materials and Methods: We conducted a retrospective study involving 71 colorectal cancer patients diagnosed between 2018 and 2020 in Khuzestan province, Iran, with known ABO blood types. Large-scale data from 29,922 blood donors in Khuzestan served as the healthy population control. The study analyzed the distribution of ABO blood groups among the blood donors.
 Results: Our findings revealed that the distribution of blood groups among colorectal cancer patients was as follows: O (31.0%), A (29.6%), B (29.6%), and AB (9.8%). However, our analysis did not establish a significant association between colorectal cancer risk and ABO antigens (P-value = 0.636) or Rh blood group (P = 0.198). Additionally, no significant differences in ABO blood types were observed concerning gender (P = 0.802), cancer type (P = 0.338), or tumor type (P = 0.207) among colorectal cancer patients.
 Conclusion: This study does not support a significant correlation between ABO and Rh blood groups and the risk of colorectal cancer, nor does it find associations with cancer type or tumor type.","PeriodicalId":94048,"journal":{"name":"International journal of hematology-oncology and stem cell research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135618383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Arsenic three oxide (As2O3) is the treatment choice for acute promyelocytic leukemia (APL). Little is known about possible risk factors with predictive value for toxicity caused by As2O3. Biomethylation is considered to be a major pathway of detoxification for inorganic arsenics (iAs). Arsenic Methyltransferase (AS3MT) is one of the key enzymes involved in the transfer of a methyl group from S-adenosyl-L-methionine to trivalent arsenical and plays a critical role in arsenic detoxification. Polymorphisms in hAS3MT lead to a change in the catalytic activity of the enzyme and may increase the risk of arsenic-related toxicity. In this study, we investigated the association of the AS3MT polymorphisms (rs11191439, rs3740390, and rs3740393) genes with hepatotoxicity in APL patients treated with As2O3.
Materials and Methods: Genotyping was performed in 140 adult patients with APL treated with As2O3 using PCR-RFLP for rs11191439 and tetra-primer ARMS-PCR for rs3740390 and rs3740393. The results of PCR-RFLP and ARMS-PCR were confirmed by direct sequencing of 10 % of DNA samples. The results were analyzed using SNPStats, SPSS, and FinchTV. Hepatotoxicity was graded according to the National Cancer Institute's Common Toxicity Criteria (CTC).
Results: Hepatotoxicity was seen in 52 of the 140 patients (37.1%), with grades I and II hepatotoxicity in 40 (28.6%) and grades III and IV hepatotoxicity in 12 (8.5%) patients. The association between the three polymorphisms and hepatotoxicity was evaluated using five genetic models and none of the three studied polymorphisms were significantly associated with hepatotoxicity.
Discussion: The results of our study showed that AS3MT rs11191439, rs3740390, and rs3740393 polymorphisms are not associated with hepatotoxicity in APL patients. Genetic polymorphisms in enzymes which are involved in arsenic metabolism have been shown to have ethnicity and race-related differences. To more precisely characterize the association between AS3MT gene polymorphism and hepatotoxicity, future large-scale studies in non-Asian populations and other ethnicities are needed.
{"title":"No Association of AS3MT Gene Polymorphisms with Susceptibility to Hepatotoxicity and in APL Patients Treated with AS2O3: A Single Center Study","authors":"Zeinab Joneidi, Yousef Mortazavi, Bahram Chahardouli, Shahrbano Rostami, Mohammad Vaezi, Majid Nabipour, Alireza Biglari, Ardeshir Ghavamzadeh","doi":"10.18502/ijhoscr.v17i4.13920","DOIUrl":"https://doi.org/10.18502/ijhoscr.v17i4.13920","url":null,"abstract":"Background: Arsenic three oxide (As2O3) is the treatment choice for acute promyelocytic leukemia (APL). Little is known about possible risk factors with predictive value for toxicity caused by As2O3. Biomethylation is considered to be a major pathway of detoxification for inorganic arsenics (iAs). Arsenic Methyltransferase (AS3MT) is one of the key enzymes involved in the transfer of a methyl group from S-adenosyl-L-methionine to trivalent arsenical and plays a critical role in arsenic detoxification. Polymorphisms in hAS3MT lead to a change in the catalytic activity of the enzyme and may increase the risk of arsenic-related toxicity. In this study, we investigated the association of the AS3MT polymorphisms (rs11191439, rs3740390, and rs3740393) genes with hepatotoxicity in APL patients treated with As2O3.
 Materials and Methods: Genotyping was performed in 140 adult patients with APL treated with As2O3 using PCR-RFLP for rs11191439 and tetra-primer ARMS-PCR for rs3740390 and rs3740393. The results of PCR-RFLP and ARMS-PCR were confirmed by direct sequencing of 10 % of DNA samples. The results were analyzed using SNPStats, SPSS, and FinchTV. Hepatotoxicity was graded according to the National Cancer Institute's Common Toxicity Criteria (CTC).
 Results: Hepatotoxicity was seen in 52 of the 140 patients (37.1%), with grades I and II hepatotoxicity in 40 (28.6%) and grades III and IV hepatotoxicity in 12 (8.5%) patients. The association between the three polymorphisms and hepatotoxicity was evaluated using five genetic models and none of the three studied polymorphisms were significantly associated with hepatotoxicity.
 Discussion: The results of our study showed that AS3MT rs11191439, rs3740390, and rs3740393 polymorphisms are not associated with hepatotoxicity in APL patients. Genetic polymorphisms in enzymes which are involved in arsenic metabolism have been shown to have ethnicity and race-related differences. To more precisely characterize the association between AS3MT gene polymorphism and hepatotoxicity, future large-scale studies in non-Asian populations and other ethnicities are needed.","PeriodicalId":94048,"journal":{"name":"International journal of hematology-oncology and stem cell research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135618529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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