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African Health Sciences Sep 2022The most frequent cytogenetic aberration is 13q14.3 deletion in Chronic Lymphocytic Leukemia (CLL). HsamiR-15a/hsa-miR-16-1 are tumor suppressor miRNAs encoded from...
BACKGROUND
The most frequent cytogenetic aberration is 13q14.3 deletion in Chronic Lymphocytic Leukemia (CLL). HsamiR-15a/hsa-miR-16-1 are tumor suppressor miRNAs encoded from 13q14.3 region.
OBJECTIVES
The aim of this study was to investigate the 13q14.3 deletion using molecular and cytogenetic techniques and association with miRNA-15a/miRNA-16-1.
MATERIALS AND METHODS
We used peripheral blood samples of 30 CLL patients who were either induced and or non-induced with DSP30+IL-2 to determine 13q14.3 deletion by karyotyping and iFISH. Expression levels of hsa-miR-15a/miR-16-1 were measured using qRT PCR and compared with deletions.
RESULTS
13q14.3 deletion was detected in 8.6% of cases by karyotyping and in 65% by iFISH. Mosaic forms (monoallelic+biallelic) were observed in 50% of cases. Besides determining common chromosome abnormalities such as add(2)(q37), t(2;7) (p11.2;q22), del(6)(q13q21), del(6)(q25), add(9)(q21), del(11)(q23), t(11;14)(q13;q32), del(13)(q11q12), del(13)(q12q14), add(14) (q23), del(14)(q23), t(14;19)(q32;q13.1), del(15)(q23), del(17)(p12), t(18;22)(q21;q11.2), add(21)(p13) and t(17;21)(q11.2;122), we also determined t(1;13)(q32;q34), inv(2)(p25q21), del(13)(q22q32), t(14;19)(q24;q13), dup(17)(q21q23), der(21;21)(p13;p13) which have not been reported previously. Mitotic index data was found statistically significant and DSP30+IL-2 increased mitotic index by 2.5 folds. Association between decreased miR-16-1 expression and deletions was statistically significant.
CONCLUSION
We suggest that cytogenetic and iFISH analyses are complementary and use of DSP30+IL-2 is effective .in CLL. Decreased expression of hsa-miR-16-1 is remarkable.
Topics: Humans; MicroRNAs; Leukemia, Lymphocytic, Chronic, B-Cell; Real-Time Polymerase Chain Reaction; Interleukin-2; Cytogenetic Analysis; Chromosome Aberrations; In Situ Hybridization, Fluorescence
PubMed: 36910369
DOI: 10.4314/ahs.v22i3.20 -
World Journal of Gastroenterology Sep 2021Multiple gastrointestinal stromal tumors (MGISTs) are specific and rare. Little is known about the impact of MGISTs on the survival of patients with gastrointestinal...
Clinicopathological characteristics and longterm survival of patients with synchronous multiple primary gastrointestinal stromal tumors: A propensity score matching analysis.
BACKGROUND
Multiple gastrointestinal stromal tumors (MGISTs) are specific and rare. Little is known about the impact of MGISTs on the survival of patients with gastrointestinal stromal tumors (GIST). The diagnosis, treatment and follow-up strategies of MGISTs is not specifically described in guidelines.
AIM
To compare the clinicopathological characteristics and prognosis of MGISTs and solitary GISTs (SGISTs).
METHODS
Patients diagnosed with primary GISTs from March 2010 to January 2020 were included. Due to the inhomogeneous distribution of several baseline characteristics and uneven MGIST and SGIST group sizes, propensity score matching was performed according to comorbidities, body mass index, tumor location, mitotic index, sex, age and American Society of Anesthesiologists score. Differences in clinicopathological characteristics and prognosis between patients with MGISTs and patients with SGISTs were compared.
RESULTS
Among the entire cohort of 983 patients, the incidence of MGISTs was 4.17%. Before matching, patients with MGISTs and those with SGISTs had disparities in body mass index, surgical approach, tumor size and mitotic index. After 1:4 ratio matching, the clinical baseline data were comparable. The 5-year progression-free survival rate was 52.17% in the MGIST group and 75.00% in the SGIST group ( = 0.031). On multivariate analysis, tumor location, tumor size, mitotic index, imatinib treatment and MGISTs (hazard ratio = 2.431, 95% confidence interval = 1.097-5.386, = 0.029) were identified as independent prognostic factors of progression-free survival. However, overall survival was similar between the SGIST and MGIST groups.
CONCLUSION
Patients with MGISTs had poorer progression-free survival than patients with SGISTs. Risk criteria and diagnostic and treatment strategies should be developed to achieve personalized precision therapy and maximize the survival benefit.
Topics: Gastrointestinal Stromal Tumors; Humans; Mitotic Index; Neoplasms, Multiple Primary; Prognosis; Propensity Score
PubMed: 34629824
DOI: 10.3748/wjg.v27.i36.6128 -
Medicine Jan 2016Clinicopathologic features and clinical outcomes of gastrointestinal stromal tumors (GISTs) in esophagus are limited, because of the relatively rare incidence of... (Comparative Study)
Comparative Study
Clinicopathologic features and clinical outcomes of gastrointestinal stromal tumors (GISTs) in esophagus are limited, because of the relatively rare incidence of esophageal GISTs. Therefore, the aim of the current study was to investigate the clinicopathologic features and clinical outcomes of esophageal GISTs, and to investigate the potential factors that may predict prognosis.Esophageal GIST cases were obtained from our center and from case reports and clinical studies extracted from MEDLINE. Clinicopathologic features and survivals were analyzed and compared with gastric GISTs from our center.The most common location was lower esophagus (86.84%), followed by middle and upper esophagus (11.40% and 1.76%). The majority of esophageal GISTs were classified as high-risk category (70.83%). Mitotic index was correlated with histologic type, mutational status, and tumor size. The 5-year disease-free survival and disease-specific survival were 65.1% and 65.9%, respectively. Tumor size, mitotic index, and National Institutes of Health risk classification were associated with prognosis of esophageal GISTs. Only tumor size, however, was the independent risk factor for the prognosis of esophageal GISTs. In comparison to gastric GISTs, the distribution of tumor size, histologic type, and National Institutes of Health risk classification were significantly different between esophageal GISTs and gastric GISTs. The disease-free survival and disease-specific survival of esophageal GISTs were significantly lower than that of gastric GISTs.The most common location for esophageal GISTs was lower esophagus, and most of the esophageal GISTs are high-risk category. Tumor size was the independent risk factor for the prognosis of esophageal GISTs. Esophageal GISTs differ significantly from gastric GISTs in respect to clinicopathologic features. The prognosis of esophageal GISTs was worse than that of gastric GISTs.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Databases, Factual; Disease-Free Survival; Esophageal Neoplasms; Female; Gastrointestinal Stromal Tumors; Humans; Male; Middle Aged; Neoplasm Invasiveness; Prognosis; Retrospective Studies; Risk Assessment; Stomach Neoplasms; Survival Analysis; Young Adult
PubMed: 26765432
DOI: 10.1097/MD.0000000000002446 -
Interactive Cardiovascular and Thoracic... May 2021Atypical carcinoids are neuroendocrine neoplasms of intermediate degree and low frequency. The aim of this study is to analyse their clinical characteristics and the...
OBJECTIVES
Atypical carcinoids are neuroendocrine neoplasms of intermediate degree and low frequency. The aim of this study is to analyse their clinical characteristics and the importance of different histopathological factors in their prognosis.
METHODS
Multicentre cooperative group EMETNE prospectively reviewed 153 patients operated on between 1998 and 2016 with diagnosis of atypical carcinoids. Clinical variables and histopathological features were assessed.
RESULTS
Mean age was 54.36 years, similar for both genders. Concerning pathological study, mean tumour size was 31.7 mm. Rosettes were presented in 17% of the cases and tumoural necrosis in 23.3%. The cell proliferation factor Ki-67 index was 10.7%. The 2- and 5-year overall survival rates were 95.8% and 88.9%, respectively. In the univariate study, statistically significant differences in survival were found for each of the categories of T, N and M factors. Mitotic index and quantification of expression of Ki-67 showed influence in overall survival, although without statistical significance. In the multivariate analysis, factors N, M and mitotic index behaved as independent prognostic factors related to survival. Median disease-free interval in the series was 163.35 months. In cases with loco-regional recurrence, 53% had positive hiliar or mediastinal nodal involvement at the time of the surgery. In the univariate analysis, we observed statistically significant differences in disease-free interval in patients with nodal involvement (P = 0.024) and non-anatomical resections (P = 0.04). Histological characteristics showed no statistically significant differences in disease-free interval.
CONCLUSIONS
Lymph node involvement, the development of distant metastasis and mitotic index, more than Ki-67 determination, were shown as independent prognostic factors related to survival of these patients.
Topics: Carcinoid Tumor; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies
PubMed: 33580683
DOI: 10.1093/icvts/ivab026 -
Cancer Science Jan 2017Metastasis and growth in neoplastic lesions requires the multistep regulation of microenvironmental factors. We aimed to elucidate the microenvironmental changes in the...
Metastasis and growth in neoplastic lesions requires the multistep regulation of microenvironmental factors. We aimed to elucidate the microenvironmental changes in the process of lymphatic metastasis of lung squamous cell carcinoma. We examined the morphological characteristics of 102 cases of primary tumor (PT), 50 of intralymphatic tumor (ILT), 51 of lymph node (LN) micrometastasis (LN-Mic; ≤2 mm in size), and 82 of LN macrometastasis (LN-Mac; ≥10 mm in size). Afterwards we evaluated the expression of nine molecules (epidermal growth factor receptor, fibroblast growth factor receptor 2, CD44, aldehyde dehydrogenase 1, Podoplanin, E-cadherin, S100A4, geminin, and ezrin) in matched PT, ILT, LN-Mic, and LN-Mac from 23 of these cases. The number of smooth muscle actin α-positive fibroblasts, CD34-positive microvessels and CD204-positive macrophages were also examined. As a result, the mitotic index of tumor cells was significantly lower in ILT and LN-Mic than PT and LN-Mac (P < 0.001). Moreover, stromal reaction in ILT and LN-Mic was less prominent than in PT and LN-Mac (P < 0.001). Immunohistochemical study revealed that epidermal growth factor receptor expression level and frequency of geminin-positive cells in ILT and LN-Mic were significantly lower than in PT and LN-Mac (P < 0.05). The number of stromal cells indicated by staining of CD34, CD204, and smooth muscle actin α in ILT and LN-Mic was also significantly lower than in PT and LN-Mac (P < 0.05). In lung squamous cell carcinoma, drastic microenvironmental changes (e.g., growth factor receptor expression and proliferative capacity of tumor cells and structural changes in stromal cells) occur during both the process of lymphatic permeation and the progression into macrometastases.
Topics: Carcinoma, Squamous Cell; Disease Progression; Epithelial-Mesenchymal Transition; ErbB Receptors; Geminin; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Lymphatic Metastasis; Macrophages; Microvessels; Mitotic Index; Myofibroblasts; Necrosis; Neoplastic Stem Cells; Stromal Cells; Transcriptome; Tumor Microenvironment
PubMed: 27761967
DOI: 10.1111/cas.13110 -
Cureus Jul 2023Introduction Despite the growing advances in molecular research and therapeutics, gliomas continue to be highly invasive and progressive tumors. There is still a need...
Introduction Despite the growing advances in molecular research and therapeutics, gliomas continue to be highly invasive and progressive tumors. There is still a need for the development of reliable prognostic biomarkers for effective therapeutic intervention. This study aims to investigate the extent of immunosuppression in glial tumors by analyzing the clinical significance of the expressions of PD-1 and FOXP3 in gliomas. Methods This is a retrospective study from 52 glioma patients who underwent surgery. Immunohistochemistry (IHC) for PD-1 and FOXP3 was performed on paraffin-embedded tissue sections manually and their expressions were noted. Data on IDH1 mutational status and mitotic index was collected and statistically analyzed. Results Immunohistochemical analysis showed that out of 52 cases, 71.15% (37/52) demonstrated cytoplasmic positivity for PD-1 and 73.1% (38/52) of the cases for nuclear FOXP3 expression. Statistical analysis suggested that elevated PD-1 and FOXP3 expressions were significantly correlated with tumor grade and increased mitotic index (P<0.05 for both the markers). Conclusion Concurrent use of checkpoint inhibitors along with other treatment modalities is being studied in a variety of solid tumors. Expressions of negative immune regulators like PD-1 and Foxp3 can pave way for a better understanding of the extent of immunosuppression in the glial tumor environment, which is imperative to formulate new therapeutic approaches.
PubMed: 37621817
DOI: 10.7759/cureus.42352 -
Brazilian Journal of Biology = Revista... 2022The search for more environmental friendly herbicides, aiming at the control of agricultural pests, combinated with less harmfulness to human health and the environment...
The search for more environmental friendly herbicides, aiming at the control of agricultural pests, combinated with less harmfulness to human health and the environment has grown. An alternative used by researchers is the application of products of secondary plant metabolism, which are investigated due to their potential bioactivities. Thus, species belonging to the Myrtaceae family are potential in these studies, since this family is recognized for having high biological activity. A species belonging to this genus is Psidium cattleyanum, which has a medicinal effect and its fruits are used in human food. Thus, the objective of this research was to evaluate and compare the phyto-cyto-genotoxicity of aqueous and ethanolic leaf extracts of the specie P. cattleyanum, from plant bioassays, as well as to identify the main classes of compounds present in the extracts. For this, the extracts were prepared, characterized and biological tests were carried out by evaluating, in seeds and seedlings of lettuce and sorghum, the variables: percentage of germination, germination speed index, root growth and aerial growth; and in meristematic lettuce cells the variables: mitotic phases, mitotic index, nuclear alterations and chromosomal alterations. Flavones, flavonones, flavonols, flavononols, flavonoids, alkaloids, resins, xanthones and anthraquinone glycoside were characterized in the ethanolic extract. Both evaluated extracts, in the highest concentration, inhibited the initial plant development. All treatments caused alterations in the mitotic phases and inhibited mitotic index. In addition, the treatments promoted an increase in nuclear and chromosomal alterations. The mechanism of action presented was aneugenic, clastogenic and determined in epigenetic alterations. The ethanolic extract was more cytotoxic, since it had a more expressive effect at a lower concentration. Despite the cytotoxicity of the extracts under study, they promoted alterations at lower levels than the glyphosate positive control.
Topics: Alkaloids; Biological Assay; Cytogenetic Analysis; Humans; Plant Extracts; Plant Leaves; Psidium
PubMed: 35674589
DOI: 10.1590/1519-6984.260985 -
Clinicopathological, Genetic and Survival Advantages of Naevus-associated Melanomas: A Cohort Study.Acta Dermato-venereologica Mar 2021Several studies have suggested that naevus-associated melanomas differ from de novo melanomas, being thinner and with less ulceration; however, the prognostic...
Several studies have suggested that naevus-associated melanomas differ from de novo melanomas, being thinner and with less ulceration; however, the prognostic implication is unclear. The objective of this study was to describe clinicopathological, genetic and survival characteristics of de novo and naevus-associated melanomas in a cohort of primary invasive cutaneous melanomas over a 20-year period. Of the 2,227 patients included in the study, 509 (22.86%) had naevus-associated melanomas. Compared with patients with de novo melanoma, they were younger, with a fairer phototype and a higher naevus count, tumours were predominantly the superficial spreading subtype, American Joint Committee on Cancer stage I, located on the trunk, and there were fewer signs of invasiveness (thinner Breslow index, less ulceration, lower mitotic index and less satellitosis). Germline mutation-al status did not show any significant association. As determined through univariate analysis, overall surviv-al was significantly better in patients with naevus- associated melanoma (hazard ratio 0.64; 95% confidence interval 0.51-0.80, p < 0.001), but multivariate analysis did not support this prognostic indication (hazard ratio 0.94; 95% confidence interval 0.75-1.18, p < 0.606). Despite this, we conclude that naevus- associated and de novo melanomas should be considered as different subtypes of melanoma.
Topics: Cohort Studies; Humans; Melanoma; Nevus; Nevus, Pigmented; Prognosis; Skin Neoplasms
PubMed: 33686449
DOI: 10.2340/00015555-3780 -
Scientific Reports Sep 2022Trifloxystrobin (TFS) is a strobilurin-type fungicide that should be investigated due to its risks to non-targeted organisms. The goal of this study was to assess the...
Trifloxystrobin (TFS) is a strobilurin-type fungicide that should be investigated due to its risks to non-targeted organisms. The goal of this study was to assess the susceptibility of Allium cepa L. to TFS in a multi-pronged approach. For 72 h, 0.2 g/L, 0.4 g/L and 0.8 g/L doses of TFS were administered to A. cepa bulbs and the control group was treated with tap water. The toxic effects of TFS were tested, considering physiological, cytogenetic, biochemical and anatomical analyses. TFS delayed growth by reducing the rooting ratio, root elongation and weight increase. Following TFS treatments, mitotic index (MI) scores decreased, while the formation of micronucleus (MN) and chromosomal aberrations (CAs) ascended. CAs types induced by TFS were listed according to their frequency as fragment, vagrant chromosome, sticky chromosome, uneven distribution of chromatin, bridge, nucleus with vacuoles, reverse polarization and irregular mitosis. TFS provoked an increment in superoxide dismutase (SOD) and catalase (CAT) enzyme activities as well as an accumulation of malondialdehyde (MDA). Meristematic cells of A. cepa roots treated with TFS had various anatomical damages, including damaged epidermis, flattened cell nucleus, damaged cortex and thickness in the cortex cell wall. All damages arising from TFS treatments exhibited dose-dependency. The findings of the present study revealed the serious toxicity of TFS in a non-targeted plant. It should not be neglected to evaluate the potential hazards of TFS with different toxicity tests.
Topics: Acetates; Allium; Antioxidants; Chromosome Aberrations; Fungicides, Industrial; Imines; Malondialdehyde; Meristem; Mitotic Index; Onions; Plant Roots; Strobilurins
PubMed: 36076029
DOI: 10.1038/s41598-022-19571-0 -
Cureus Jul 2023Investigating haloperidol's cytogenetic behavior in cultured human T lymphocytes of patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).
OBJECTIVES
Investigating haloperidol's cytogenetic behavior in cultured human T lymphocytes of patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).
METHODS
Four haloperidol solutions were added in cultures of peripheral blood lymphocytes of healthy individuals, SLE, and RA patients. After 72 hours of incubation, the cultured lymphocytes were plated on glass slides, and stained with the fluorescence plus Giemsa method, and sister chromatid exchanges (SCEs), proliferation rate index (PRI), and mitotic index (MI) were measured with the optical microscope.
RESULTS
Result analysis revealed: (a) a statistically significant (p=0.001) dose-dependent increase of SCEs in SLE patients compared to healthy individuals; (b) a statistically significant (p=0.001) dose-dependent decrease of SCEs in RA patients for haloperidol concentrations 5, 10μg/mL; (c) a statistically significant (p=0.001) dose-dependent increase of SCEs in RA patients for haloperidol concentrations 20, 100μg/mL; and (d) a statistically significant (p=0.001) dose-dependent reduction of PRI and MI in both patient groups compared to healthy individuals. Furthermore, a correlation was observed between (a) SCE and PRI index variations, (b) MI and SCE index variations, and (c) PRI and MI index variations.
CONCLUSIONS
Haloperidol affects T lymphocytes from SLE and RA patients by modifying DNA replication procedures, DNA damage response, and ferroptosis. Considering the wide use of haloperidol in neuropsychiatric symptoms of SLE and RA patients, further studies with more immune cell subsets are needed to evaluate its effects on human genetic material.
PubMed: 37609095
DOI: 10.7759/cureus.42283