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It seems that schwannomas of the tongue base originate from branches of the glossopharyngeal, vagus, or hypoglossal nerves. Additionally, complete trans-oral surgical excision is an efficient method to remove them.
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OBJECTIVES: We aimed to determine possible association between heterogeneity of Helicobacter pylori cytotoxin-associated gene pathogenicity island and gene expression profiles in patients with distinct histopathological changes. METHODS: Gastric biopsies were obtained from seventy five patients. Microbiological and pathological examinations were done and intactness of Helicobacter pylori cagPAI was determined by PCR using 11 pairs of primers flanking cagζ-cagA regions and cagPAI empty site. Alterations at mRNA levels of eight genes were investigated by real-time PCR and their association with cagPAI intactness and histopathological changes examined statistically. RESULTS: A larger proportion of cagPAI positive strains colonized patients with SAG (52.4%), followed by CG (33.3%), and IM (14.3%). Intact cagPAI was found in 87.5% of the strains obtained from patients with SAG, while significantly lower frequency was detected among those with CG (12.5%) and IM (0%). No significant difference was found among the studied histological groups and fold changes in gene expression of gastric biopsies of Helicobacter pylori infected patients with distinct cagPAI status. However, in each histological group, the strains with more complete gene cluster induced (ErbB2, CCNE1, CTNNB1, and MMP7 in SAG and IM groups) or reduced (TP53, in CG group) expression of the GC associated genes in relatively higher levels. APC, TP53 and E-cadherin were down-regulated in patients with SAG and IM compared with CG patients, irrespective to the status of cagPAI integrity. CONCLUSIONS: Helicobacter pylori strains that carry more complete cagPAI segment could induce remarkably higher levels of mRNA changes of GC associated genes in all histopathological groups.
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Helicobacter pylori , Neoplasias Gástricas , Humanos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologia , Helicobacter pylori/genética , Helicobacter pylori/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Expressão GênicaRESUMO
BACKGROUND: This study aimed to evaluate the expression of Liver X receptor (Lxr), Sirtuin 1 (Sirt1), apoptotic-related genes, and the protective role of N-acetylcysteine (NAC) in the liver of rats treated with Lead (Pb). METHODS: Rats were randomly divided into 5 groups, including G1 (control), G2 (single dose of Pb), G3 (continuous dose of Pb), G4 (single dose of Pb + NAC), and G5 (continuous dose of Pb + NAC). Lipid profiles and liver specific enzymes were assessed. Expression of Lxr, Sirt1, Bax and Caspase-3 genes was considered using RT-PCR. RESULTS: Exposure to Pb caused a significant accumulation of Pb in the blood and liver tissue, increase in serum AST, ALT and ALP enzymes, as well as lipid profiles. Chronic exposure to Pb caused a significant decrease in Lxr (3.15-fold; p < 0.001) and Sirt1 (2.78-fold; p = 0.009), but significant increase in expression of Bax (4.49-fold; p < 0.001) and Caspase-3 (4.10-fold; p < 0.001) genes when compared to the control. Combined therapy with Pb + NAC in rats caused a significant decrease in AST, ALT and ALP values (28.93%, 20.80% and 28.86%, respectively) in the blood as compared to rats treated with Pb alone. Co-treated with Pb + NAC significantly increased the expression of Lxr (1.72-fold; p = 0.043) and Sirt1 (2.45-fold; p = 0.008), but decreased the expression of Bax (1.96-fold; p = 0.03) and Caspase 3 (2.22-fold; p = 0.029) genes when compared to rats treated with Pb alone. CONCLUSION: Chronic exposure to Pb is strongly associated with accumulation of Pb in the blood and liver, hepatic cells apoptosis, down-expression of Lxr and Sirt1 genes and consequently liver injury and abnormal lipid profiles. NAC reversed the Pb-induced toxicity on the liver tissue.
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Acetilcisteína , Sirtuína 1 , Acetilcisteína/farmacologia , Animais , Caspase 3/genética , Caspase 3/metabolismo , Chumbo/metabolismo , Lipídeos , Fígado/metabolismo , Receptores X do Fígado/genética , Receptores X do Fígado/metabolismo , Ratos , Sirtuína 1/genética , Sirtuína 1/metabolismo , Sirtuína 1/farmacologia , Proteína X Associada a bcl-2/metabolismo , Proteína X Associada a bcl-2/farmacologiaRESUMO
BACKGROUND: ACTH-independent macronodular hyperplasia (AIMAH) is an uncommon disorder characterized by massive enlargement of both adrenal glands and hypersecretion of cortisol. Concomitant AIMAH and multiple endocrine neoplasia type1 (MEN1) is rare to our knowledge. CASE PRESENTATION: Herein, we describe a 32 year old woman with long history of prolactinoma and secondary ammonhrea presented with not-severe manifestation of hypoglycemia due to concomitant presence of insulinoma with AIMAH leading to 12 years delay of MEN1 diagnosis. Laboratory tests showed severe hypoglycemia associated with hyper insulinemia (non-fasting blood sugar = 43 mg/dl, insulin = 80.6 µIU /ml, C-peptide = 9.3 ng/ml) hyperparathyroidism (calcium = 10.3 mg/dl, phosphor = 3.1 mg/dl, PTH = 280 pg/ml) and chemical evidence of an ACTH-independent hypercortisolism (serum cortisol value of 3.5, after 1 mg dexamethasone suppression test serum ACTH value of 17 pg/ml, and high urinary cortisol level). Abdominal CT scan demonstrated two enhancing well-defined masses 27*20 mm and 37*30 mm in the tail and body of the pancreas, respectively, and a 36*15 mm mass in left adrenal gland (seven Hounsfield units). Dynamic pituitary MRI revealed a partial empty sella. The physical examination of the patient was unremarkable. Distal pancreatectomy and a left adrenalectomy were performed. After the surgery, we observed clinical and biochemical remission of hyper insulinemia and gradual decrease in urinary cortisol. The histological features of the removed left adrenal gland were consistent with AIMAH. Histological examination of the pancreatic lesions revealed well differentiated neuroendocrine tumors. Genetic abnormalities in the MEN1, heterozygote for pathogenic variant chr11; 645,773,330-64577333AGAC, c.249-252delGTCT, p. (11e85Serfs Ter33) in exon 2 were found. It was recommended the patient undergoes parathyroidectomy as soon as possible. CONCLUSION: Given the history and presentation of our case, we recommend that the clinicians consider the possibility of autonomous cortisol production in MEN1 patients who do not show severe symptoms of hypoglycemia in the presence of insulinoma.
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Hipoglicemia , Insulinoma , Neoplasia Endócrina Múltipla , Neoplasias Pancreáticas , Neoplasias Hipofisárias , Glândulas Suprarrenais/patologia , Hormônio Adrenocorticotrópico , Adulto , Síndrome de Cushing , Feminino , Humanos , Hidrocortisona , Hiperplasia/patologia , Hipoglicemia/diagnóstico , Hipoglicemia/etiologia , Hipoglicemia/patologia , Insulinoma/complicações , Insulinoma/diagnóstico , Insulinoma/cirurgia , Neoplasia Endócrina Múltipla/patologia , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/cirurgiaRESUMO
TGF-ß signaling pathways promote tumour development and control several downstream genes such as CTGF and MMPs. This study aimed to investigate the association between CTGF and MMP-1 mRNA expressions with clinicopathological status and survival rate in colorectal cancer patients. We investigated expression levels of CTGF and MMP-1 genes in paraffin-embedded tumours and adjacent normal tissue blocks (ADJ) by Real Time-PCR. Then, the expression of Smad2 and Smad4 proteins in the TGF-ß canonical pathway was evaluated by immunohistochemistry. Finally, the correlation between CTGF, MMP-1, and the canonical TGF-ß-signalling pathway with the clinicopathological features was investigated. Expression levels of MMP-1and CTGF were higher in tumours compared with adjacent normal tissues. Overexpression levels of MMP-1 and CTGF were associated with lymph node metastasis, distant metastasis, tumour histopathological grading, advanced stage, and poor survival (p < 0.05). Additionally, a significant association between the upregulation of MMP-1 and tumour location was noted. Upregulation of Smad2 and Smad4 proteins were also significantly correlated with lymph node metastasis, distant metastasis, advanced stage, and poor survival (p < 0.0001). This study showed that canonical TGF-ß signalling regulates both CTGF and MMP-1 expression and CRC progression. Moreover, TGF-ß signalling and its downstream genes could be used as novel biomarkers and novel approaches for targeted therapy in CRC.
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Neoplasias Colorretais , Fator de Crescimento do Tecido Conjuntivo , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Humanos , Metástase Linfática , Metaloproteinase 1 da Matriz/genética , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismoRESUMO
We aimed to investigate mitigating effects of N-acetylcysteine (NAC) on the oxidative stress, apoptosis and Parkinson's disease (PD)-related genes in the brain tissue of male rats exposed to continuous doses of cadmium and lead. Rats were randomly divided into five groups, including G1 (control), G2 (continuous dose of Cd), G3 (continuous dose of Pb), G4 (continuous dose of Cd + NAC), and G5 (continuous dose of Pb + NAC). Biomarkers of oxidative stress, malondialdehyde (MDA), and total antioxidant capacity (TAC) were measured. Expression of PD- and apoptosis-related genes was considered using RT-PCR. Chronic exposure to these heavy metals was associated with accumulation of Pb and Cd in the brain and blood and caused severe morphological changes in the brain, as well as decreased body and brain weights. Continuous exposure to Cd and Pb significantly decreased TAC content and SOD expression but increased MDA level in the brain tissues (P < 0.001). A significant increase was observed in expression of PD-related genes, Parkin, Pink1, LRRK2, SNCA, and Caspase-3 in the brain tissues following exposure to Cd and Pb. Pb exhibited stronger toxicity on the brain tissue compared to Cd. NAC supplementation not only improved morphological changes, but also compensated antioxidant capacity and expression of apoptosis- and PD-related genes in the brain tissues when compared to rats exposed to Pb and Cd alone. Chronic exposure to Pb and Cd is strongly associated with accumulation of these heavy metals in the brain, morphological changes, antioxidants depletion, oxidative stress, and brain cells apoptosis. Changes in expression of PD-related genes indicate the higher risk of PD among individuals who are chronically exposed to these heavy metals. NAC can protect brain tissue against Pb and Cd toxicity by elevating antioxidants capacity, mitigating oxidative stress, apoptosis, and down-regulating of PD-related genes.
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Acetilcisteína , Metais Pesados , Acetilcisteína/farmacologia , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Encéfalo/metabolismo , Cádmio/toxicidade , Suplementos Nutricionais , Chumbo/toxicidade , Masculino , Metais Pesados/farmacologia , Estresse Oxidativo , RatosRESUMO
This study aimed to consider the expression of Nrf2, NLRP3 and caspase 1 genes, as well as oxidative stress, and the protective role of N-acetyl cysteine (NAC) in the liver of rats treated with cadmium (Cd). Male rats were randomly divided into five groups including G1 (control), G2 (single dose of Cd), G3 (continuous dose of Cd), G4 (single dose of Cd + NAC), and G5 (continuous dose of Cd + NAC). Levels of malondialdehyde (MDA) and total antioxidant capacity (TAC) were measured. Expression of Nrf2, NLRP3 and caspase 1 genes was considered using RT-PCR. NAC treatments significantly improved TAC, but decreased MDA values in rats that exposed to continuous dose of Cd (p<0.05). Exposure to continuous dose of Cd caused a significant decrease in Nrf2 expression by 2.46-fold (p<0.001), but enhanced expression of NLRP3 and Caspase 1 genes by 3.13-fold and 3.16-fold), respectively (p<0.001). Compared to rats that treated to continuous dose of Cd, NAC supplementation enhanced the expression of Nrf2 by 1.67-fold (p<0.001) and reduced the expression of NLRP3 and Caspase 1 genes by 1.39-fold (p<0.001) and 1.58-fold (p<0.001), respectively. Down-regulation of Nrf2 and overexpression of NLRP3 and caspase 1 seems to be one of the main mechanisms of Cd toxicity on liver tissue. NAC protects liver tissue against Cd-induced oxidative injuries via enhancement of Nrf2 expression and reduction of NLRP3 and caspase 1 genes.
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OBJECTIVE: B lymphocyte infiltration in the tumor microenvironment has been proposed to play pivotal roles in tumor progression. Heat shock protein 70 (HSP70) expressed by tumor cells can induce antitumor immune response. Few studies have examined the clinicopathologic relationship between tumor infiltrating B lymphocyte and HSP70 expression in human cancer. So far, there is no complete knowledge on the relationship in oral squamous cell carcinoma (OSCC). The present study was conducted to evaluate the relationship between tumor infiltrating B lymphocyte and HSP70 expression in OSCC, as well as the clinical outcome. MATERIALS AND METHODS: In this retrospective study, the immunohistochemical analysis of 50 OSCC specimens was performed using CD20 and HSP70 antibodies. The relationship between markers' expression and clinicopathologic data was evaluated using Mann-Whitney test, Chi-square test, logistic regression model, and Spearman's correlation coefficient. RESULTS: The data analysis showed significant correlation between peritumoral CD20+ B lymphocyte infiltration and lymph node metastasis (P = 0.047). Furthermore, HSP70 expression was significantly correlated with stage (P = 0.003), lymph node metastasis (P < 0.001), and tumor size (P = 0.044). However, no relationship was observed between B lymphocyte infiltration and HSP70 expression. CONCLUSION: The results suggest that peritumoral B lymphocyte infiltration and HSP70 expression level have significant association with OSCC and may be considered as prognostic indicators in OSCC. Thus, evaluation of B cells as therapeutic targets in OSCC patients is recommended.
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To evaluate the cytotoxicity effects of luteolin (LUT) and kaempferol (KAE) via reactive oxygen species (ROS) mediated mitochondrial targeting on hepatocytes obtained from the liver of hepatocellular carcinoma (HCC) rats. In this study, HCC induced by diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF). In the following, rat liver hepatocytes and mitochondria were isolated and tested for every eventual apoptotic and anti-HCC effects of LUT and KAE. The results of MTT assay showed that LUT and KAE were able to induce selective cytotoxicity in hepatocytes of HCC group in a dose- and time-dependent manner. Treatment of mitochondria from hepatocytes of HCC group with LUT and KAE were accompanied by loss of mitochondrial membrane potential (MMP) and mitochondrial swelling and release of cytochrome c (P < 0.001) via reactive oxygen species (ROS) generation before cytotoxicity ensued. LUT and KAE also increased activation of caspase-3 (P < 0.001 and P < 0.01, respectively). Flow-cytometry analysis indicated that the mode of cell death induced by these flavonoids were mostly apoptosis. Importantly, LUT and KAE were nontoxic for healthy hepatocytes and mitochondria. Therefore, we suggest that LUT and KAE are a good candidate for the complementary therapeutic agent against HCC.
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Antineoplásicos Fitogênicos/farmacologia , Hepatócitos/efeitos dos fármacos , Quempferóis/farmacologia , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Luteolina/farmacologia , 2-Acetilaminofluoreno/toxicidade , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Citocromos c/metabolismo , Dietilnitrosamina/toxicidade , Relação Dose-Resposta a Droga , Hepatócitos/patologia , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/patologia , Masculino , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias Hepáticas/patologia , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: Ameloblastoma is a benign, slow-growing and locally invasive tumor. It is one of the most prevalent odontogenic tumors, with an incidence rate of 1% of all oral tumors and approximately 18% of odontogenic tumors. A group of genes have been investigated in patients with ameloblastoma. The BRAF V600E mutation has been implicated as the most common mutation in ameloblastoma. The presence or absence of this mutation has been associated with several clinicopathological properties, including location, age at diagnosis, histology, and prognosis. Although some populations have been investigated so far, little data are available on the Iranian population. The current research was launched to study the BRAF V600E mutation among a cohort of Iranian patients with ameloblastoma. METHODS: In this clinicopathological and molecular biology study, a total of 19 formalin-fixed, paraffin-embedded tissues were studied. DNA extraction was performed, followed by PCR-sequencing of exons 10 and 15 of the BRAF gene to identify mutations. In silico analysis was performed for the identified variants. Results were analyzed by T test, Chi-square, and Fisher's exact test. RESULTS: Totally, 12 of 19 samples (63%) harbored the p. V600E hotspot mutation. In addition, we identified several variants, two of which were novel. The c.1769T>G (p. V590G) and c.1751C>T (p.L584F) as the novel variants showed a possible damaging effect by in silico analysis. No variant was found within exon 10. CONCLUSIONS: Our study confirms the role of BRAF mutations in ameloblastoma in the Iranian patients studied.
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Ameloblastoma/genética , Predisposição Genética para Doença , Neoplasias Bucais/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , DNA de Neoplasias/isolamento & purificação , Éxons , Feminino , Frequência do Gene , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
INTRODUCTION: Familial adenomatous polyposis (FAP) may be associated with some extracolonic manifestations which in this vein, it is known as Gardner's syndrome. To our knowledge, so far, there is no report of mucinous cystadenoma in association with FAP. CASE PRESENTATION: We report a 31-year-old woman with FAP who underwent total proctocolectomy with ileal pouch-anal anastomosis 5 years earlier. During endoscopic surveillance, she was found to have a submucosal lesion in rectal cuff. RESULTS: Endoscopic ultrasound (EUS) revealed a round submucosal anechoic lesion measuring about 3 cm originating from the second layer of the rectal cuff. Surgical resection was performed and a cystic tumor was removed. Histologic examination was consistent with mucinous cystadenoma. CONCLUSION: FAP can be associated with mucinous cystadenoma.
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Polipose Adenomatosa do Colo/patologia , Cistadenoma Mucinoso/patologia , Reto/patologia , Adulto , Endoscopia , Feminino , Humanos , Mucosa/patologiaRESUMO
BACKGROUND: hepatocellular carcinoma (HCC) is the third cause of mortality due to cancer throughout the world. OBJECTIVE: The main goal of the current research was to evaluate the selective toxicity of apigenin (APG) on hepatocytes and mitochondria obtained from the liver of HCC rats). METHOD: In this research, HCC induced by a single dose of diethylnitrosamine (DEN); 200 mg/kg, i.p, and 2-acetylaminofluorene (2-AAF) (0.02%, through dietary) for 14 days. For confirmation of HCC, histopathological evaluations and determination of serum concentrations of liver toxicity enzymes and specific liver cancer marker; alpha-fetoprotein (AFP) were performed. Then, cancerous and non- cancerous hepatocytes were isolated by using the collagen perfusion method. Eventually, mitochondria isolated from HCC and normal hepatocytes were tested for every eventual toxic effects of APG. RESULTS: After confirmation of HCC, the results of this research showed that APG (10, 20 and 40 µM) increased mitochondrial parameters such as, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) level, mitochondrial swelling and cytochrome c expulsion only in cancerous hepatocytes. Apoptotic effect of APG on HCC cells was confirmed by caspase-3 activation and Annexin V-FITC and PI double staining analysis. CONCLUSION: These results propose the eligibility of the flavonoid APG as a complementary therapeutic agent for patients with hepatocellular carcinoma.
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Antineoplásicos/farmacologia , Apigenina/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Animais , Antineoplásicos/química , Apigenina/química , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Neoplasias Hepáticas/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-AtividadeRESUMO
Osteoporosis (OP) and osteoporotic fracture are major public health issues for society; the burden for the affected individual is also high. Previous studies have shown that pulsed wave low-level laser therapy (PW LLLT) has osteogenic effects. This study intended to evaluate the impacts of PW LLLT on the cortical bone of osteoporotic rats' tibias in two experimental models, ovariectomized and dexamethasone-treated. We divided the rats into four ovariectomized induced OP (OVX-d) and four dexamethasone-treated (glucocorticoid-induced OP, GIOP) groups. A healthy (H) group of rats was considered for baseline evaluations. At 14 weeks following ovariectomy, we subdivided the OVX-d rats into the following groups: (i) control which had OP, (ii) OVX-d rats treated with alendronate (1 mg/kg), (iii) OVX-d rats treated with LLLT, and (iv) OVX-d rats treated with alendronate and PW LLLT. The remaining rats received dexamethasone over a 5-week period and were also subdivided into four groups: (i) control rats treated with intramuscular (i.m.) injections of distilled water (vehicle), (ii) rats treated with subcutaneous alendronate injections (1 mg/kg), (iii) laser-treated rats, and (iv) rats simultaneously treated with laser and alendronate. The rats received alendronate for 30 days and underwent PW LLLT (890 nm, 80 Hz, 0.972 J/cm(2)) three times per week during 8 weeks. Then, the right tibias were extracted and underwent a stereological analysis of histological parameters and real-time polymerase chain reaction (RT-PCR). A significant increase in cortical bone volume (mm(3)) existed in all study groups compared to the healthy rats. There were significant decreases in trabecular bone volume (mm(3)) in all study groups compared to the group of healthy rats. The control rats with OP and rats from the vehicle group showed significantly increased osteoclast numbers compared to most other groups. Alendronate significantly decreased osteoclast numbers in osteoporotic rats. Concurrent treatments (compounded by PW LLLT and alendronate) produce the same effect on osteoporotic bone.
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Terapia com Luz de Baixa Intensidade , Osteoporose/radioterapia , Tíbia/efeitos da radiação , Alendronato/farmacologia , Alendronato/uso terapêutico , Animais , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Regeneração Óssea/efeitos da radiação , Diáfises/efeitos da radiação , Feminino , Humanos , Masculino , Osteogênese , Osteoporose/patologia , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Tíbia/patologia , TranscriptomaRESUMO
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. In patients for whom HCC could not be detected early, current treatments show poor tolerance and low efficacy. So, alternative therapies with good efficacy are urgently needed. The aim of this research was to evaluate the selective apoptotic effects of myricetin (MYR), a flavonoid compound, on hepatocytes and mitochondria obtained from the liver of HCC rats. In this study, HCC induced by diethylnitrosamine (DEN), as an initiator, and 2-acetylaminofluorene (2-AAF), as a promoter. To confirm the HCC induction, serum levels of alpha-fetoprotein (AFP), AST, AST and ALP and histopathological changes in the liver tissue were evaluated. Rat liver hepatocytes and mitochondria for evaluation of the selective cytotoxic effects of MYR were isolated, and mitochondrial and cellular parameters related to apoptosis signalling were then determined. Our results showed that MYR was able to induce cytotoxicity only in hepatocytes from the HCC but not from the untreated control group. Besides, MYR (12.5, 25 and 50 µM) induced a considerable increase in reactive oxygen species (ROS) level, mitochondrial swelling, mitochondrial membrane permeabilization (MMP) and cytochrome c release only in cancerous but not in untreated normal hepatocyte mitochondria. MYR selectively increased caspase-3 activation and apoptotic phenotypes in HCC, but not untreated normal hepatocytes. Finally, our finding underlines MYR as a promising therapeutic candidate against HCC and recommends the compound for further studies.
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Apoptose/efeitos dos fármacos , Flavonoides/farmacologia , Hepatócitos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , 2-Acetilaminofluoreno/toxicidade , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Aspartato Aminotransferases/sangue , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/tratamento farmacológico , Caspase 3/metabolismo , Citocromos c/metabolismo , Dietilnitrosamina/toxicidade , Modelos Animais de Doenças , Fígado/citologia , Fígado/efeitos dos fármacos , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Dilatação Mitocondrial/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , alfa-Fetoproteínas/metabolismoRESUMO
CONTEXT: Liver damage is relatively common in patients affected by HL, but paraneoplastic cholestasis is an uncommon presenting symptom in HL. CASE REPORT: We report the case of a 38-year-old man who came to our hospital with jaundice, pruritis, nausea, vomiting, weight loss, and recurrent episodes of fever without any hepatosplenomegaly or lymphadenopathy. Laboratory findings showed abnormal liver functioning with mixed hepatocellular and cholestatic patterns. Sonographic evaluation of the biliary tract was normal. We ruled out viral infections, autoimmune process, and hemochromatosis. The patient was put on ursobile and NAC (N-acetyl-systeine) and prednisolone treatment. In magnetic resonance cholangiopancreatography examination, there were multiple strictures in the intrahepatic and extrahepatic bile ducts with mild dilatation. Histologic finding of liver biopsy was compatible with sclerosing cholangitis or drug-induced cholestasis. General condition and laboratory examination results of the patient became better, but we found lymph-adenopathy on monthly follow-up examination. Histological finding of the lymph node was compatible with HL. CONCLUSION: This report emphasizes that HL can be presented with different paraneoplastic symptoms and that one of them is secondary sclerosing cholangitis. It has better prognosis than vanishing bile duct syndrome, and perhaps steroid treatment can be suggested.
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BACKGROUND Ameloblastic fibrosarcoma (AFS) is a rare malignant odontogenic tumor with a mesenchymal component, showing sarcomatous features and epithelial nests resembling ameloblastic fibroma (AF). CASE REPORT We report a case of AFS showing epithelial dysplasia arising in a recurrent AF in the left mandible after 3 years in a 26-year-old man, which is regarded as an uncommon histopathologic finding in AFS. We also emphasize the comprehensive clinical, radiographic, and histopathologic evaluation, and immunohistochemical staining of this patient. CONCLUSIONS We conclude that it is important to consider malignancy alternations in the epithelial component of AFS, along with that of the mesenchymal component, to provide a proper diagnosis and treatment of recurrent AF.
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Fibroma/patologia , Fibrossarcoma/diagnóstico , Neoplasias Mandibulares/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Tumores Odontogênicos/diagnóstico , Adulto , Fibroma/cirurgia , Fibrossarcoma/cirurgia , Humanos , Irã (Geográfico) , Masculino , Neoplasias Mandibulares/cirurgia , Recidiva Local de Neoplasia/cirurgia , Tumores Odontogênicos/cirurgiaRESUMO
BACKGROUND: Tendon healing is impaired in patient with diabetes mellitus. The effects of streptozotocin-induced type 1 diabetes (STZ-D) on the healing of the transected Achilles tendon in rats was studied. METHODS: In the experimental group, type one diabetes was induced via administration of STZ. The right Achilles tendon of all the rats was transected 30 days after the STZ administration. The Achilles tendons were examined for biomechanical and histological examinations. RESULTS: The statistical analysis showed that Young's modulus of elasticity and stress tensile load of the control group were significantly higher than those of the experimental group, and inflammation in the experimental group was significantly higher than that in the control group. At the same time, fibrosis in the experimental group was significantly lower than that of the control group. CONCLUSION: Induction of type 1 diabetes by STZ significantly delayed the healing of the transected Achilles tendon in rats.
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Tendão do Calcâneo/lesões , Diabetes Mellitus Experimental/fisiopatologia , Traumatismos dos Tendões/patologia , Traumatismos dos Tendões/fisiopatologia , Cicatrização/fisiologia , Animais , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Experimental/patologia , Modelos Animais de Doenças , Módulo de Elasticidade , Masculino , Ratos , Ratos Wistar , Recuperação de Função Fisiológica , Estreptozocina , Traumatismos dos Tendões/cirurgia , Resistência à Tração , Fatores de Tempo , Suporte de CargaRESUMO
Dracocephalum kotschyi Boiss. (Labiatae) is a native Iranian medicinal plant which has been used in combination with Peganum harmala L. as a remedy for many forms of human cancer especially leukemia and gastrointestinal malignancies. Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. In this investigation HCC was induced by a single intraperitoneal injection of diethylnitrosamine (DEN) in corn oil at 200 mg/kg body weight to rats. Two weeks after DEN administration, cancer development was promoted with dietary 2-acetylaminofluorene (2-AAF) (0.02%, w/w) for 2 weeks. Serum alpha-fetoprotein (AFP) concentration, serum alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) activities were also determined for confirmation of hepatocellular carcinoma induction. Then rat hepatocytes were isolated with collagen perfusion technique and tumoral hepatocytes were sorted by flow cytometry. Finally isolated mitochondria obtained from both tumoral and nontumoral hepatocytes were used for any probable toxic effect of Dracocephalum kotschyi ethanolic extract. Our results showed that D. kotschyi extract (250 µg/mL) induced reactive oxygen species (ROS) formation, mitochondrial membrane permeabilization (MMP), and mitochondrial swelling and cytochrome c release only in tumoral but not nontumoral hepatocyte. These findings propose Dracocephalum kotschyi as a promising candidate for future anticancer research.
Assuntos
Antioxidantes/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Animais , Antioxidantes/química , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/patologia , Permeabilidade da Membrana Celular/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Humanos , Lamiaceae/química , Peroxidação de Lipídeos/efeitos dos fármacos , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/patologia , Masculino , Mitocôndrias/patologia , Membranas Mitocondriais/efeitos dos fármacos , Extratos Vegetais/química , Ratos , Espécies Reativas de Oxigênio/metabolismoRESUMO
Calcifying cystic odontogenic tumor (CCOT) demonstrates considerable diversity in histopathology and clinical behavior. Ghost cell odontogenic carcinoma (GCOC) is the rare malignant counterpart of CCOT and it frequently arises from malignant transformation of a recurrent CCOT. In this paper, we present a case of CCOT and discuss its distinct histopathologic features in recurrence. Then, we will have a review on clinical, histopathological, and immunohistochemical aspects of GCOC in the literature. Predictive factors of malignant transformation in a benign CCOT will also be discussed.
RESUMO
Laryngeal adenosquamous carcinoma (ASC) is a rare malignancy, and the problems in true diagnosis of this entity are well known. In this paper, we describe a case of ASC and discuss its distinct histopathology in metastatic lymph nodes. A heavy smoker man presented with a progressive neck mass. Based on incisional biopsy, diagnosis of squamous cell carcinoma (SCC) was made and total laryngectomy with bilateral radical neck dissection was performed. Sections of primary tumor showed a well-differentiated SCC. However, lymph node metastases had a distinct feature of glandular structures. Further investigation with Mayer's mucicarmine stain confirmed the presence of rare scattered glands in primary tumor and the final diagnosis was changed to ASC. Adenosquamous carcinoma is a distinct entity and must be distinguished from the common SCC of larynx. As a result, when a lesion with diagnosis of squamous cell carcinoma shows evidence of glandular differentiation in a subsequent biopsy or in nodal metastases, more investigation is necessary. Moreover, the glandular structures in primary tumor, as in this case, may be rare and inconspicuous. Therefore, we suggest the precise evaluation of metastatic lymph nodes for any laryngeal tumor with diagnosis of SCC. This helps to make appropriate therapeutic decisions with respect to the aggressive behavior of ASC and its high propensity for lymph node metastasis.