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BACKGROUND: Human papillomavirus (HPV) is associated with different malignancies but its role in the pathogenesis of ovarian cancer is controversial. This study investigated the prevalence, genotyping and physical state of HPV in ovarian cancer Saudi patients. METHODS: Hundred formalin fixed paraffin embedded (FFPE) ovarian carcinoma tissues and their normal adjacent tissues (NAT) were included in the study. HPV was detected by nested polymerase chain reaction (PCR) using degenerated HPVL1 consensus primer pairs MY09/MY11 and GP5+/GP6 + to amplify a broad spectrum of HPV genotypes in a single reaction. The HPV positive samples were further genotyped using DNA sequencing. The physical state of the virus was identified using Amplification of Papillomavirus Oncogene Transcripts (APOT) assay in the samples positive for HPV16 and/or HPV18. RESULTS: High percentage of HPV (42%) was observed in ovarian carcinoma compared to 8% in the NAT. The high-risk HPV types 16, 18 and 45 were highly associated with the advanced stages of tumor, while low-risk types 6 and 11 were present in NAT. In malignant tissues, HPV-16 was the most predominant genotype followed by HPV-18 and -45. The percentage of viral integration into the host genome was significantly high (61.1%) compared to 38.9% episomal in HPV positive tumors tissues. In HPV18 genotype the percentage of viral integration was 54.5% compared to 45.5% episomal. CONCLUSION: The high risk HPV genotypes in ovarian cancer may indicate its role in ovarian carcinogenesis. The HPV vaccination is highly recommended to reduce this type of cancer.
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Neoplasias Ovarianas/virologia , Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Integração Viral , Adulto , Idoso , Primers do DNA/genética , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/etiologia , Papillomaviridae/fisiologia , Infecções por Papillomavirus/complicações , Reação em Cadeia da Polimerase , Prevalência , Arábia Saudita/epidemiologia , Análise de Sequência de DNARESUMO
Subepithelial lesions (SELs) originating from muscularis mucosae of the colon are very rare findings on endoscopy. Appropriate management of SELs involves making a correct diagnosis and estimating their malignant potential. In this case study, a 58-year-old Saudi man presented with a small, 8-mm sigmoid polyp during screening colonoscopy. The polyp was removed by hot snare polypectomy and sent to pathology laboratory. Report showed an unremarkable colonic mucosa and underlying well-circumscribed submucosal lesion composed of monotonous spindle cells. Immunohistochemical (IHC) analysis ruled out CD117-/DOG1-positive GIST and confirmed the lesion as leiomyomatous polyp. Colonic leiomyomas are usually benign and often asymptomatic and discovered during CRC screening procedures. Diagnosis is made on histology/IHC analysis since endoscopically they might be indistinguishable from other SELs. Conventional polypectomy is an appropriate treatment for small colonic leiomyoma and these benign lesions typically do not recur.
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Hyaline fibromatosis syndrome (HFS) is a rare, autosomally-recesfvsive disease characterized by papulonodular skin lesions, soft tissue masses, joint contractures, gingival overgrowth, and osteolytic bone lesions. Mutations in capillary morphogenesis gene 2 are responsible for both these conditions. Generally, an autosomal recessive pattern is assumed to be the most common mode of inheritance. Here, we report an unusual case of a twenty-three-year-old female patient with HFS who reported with a chief complaint of growing nasal mass for three months. There was no history of pain or bleeding associated with the nasal mass. Due to the growing mass, she experienced right nasal obstruction, which compromised her quality of life. There was an unremarkable family history. Her physical examination revealed multiple asymptomatic pinkish-white papulonodular lesions located at multiple sites. Intra orally, she had generalized gingival enlargement. Her nasal examination revealed a right sided nasal mass, bright red in color. The lesion was soft on palpation. All the results of hematological and biochemical tests were normal. However, skeletal radiographic examination showed the joint contractures on her knees and elbows without the presence of osteolytic bone lesions. The nasal lesion was surgically excised and histopathological examination revealed features suggestive of HFS.
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BACKGROUND: Hepatic steatosis in hepatitis C virus (HCV)-infected patients has been shown to enhance the progression of liver fibrosis and decrease the response to antiviral therapy. AIMS: We aimed to determine the role of HCV genotype 4 (HCV-G4) in the prevalence of hepatic steatosis, its impact on antiviral therapy, and its associations and predictive factors in comparison to HCV-G1-infected patients. METHODS: Treatment-naïve HCV patients who were started on pegylated interferon a-2b plus ribavirin therapy in two centers in Saudi Arabia were included. The severity of steatosis was assessed using the METAVIR and NAS (non-alcoholic fatty liver disease [NAFLD] activity score) scoring systems. Sustained virological response (SVR) was studied in relation to the degree of steatosis. Associations between steatosis and multiple demographic, laboratory, and virological factors were examined. HCV-G1 and HCV-G4 patients were compared. RESULTS: A total of 116 patients (HCV-G4 85 [73.3%]; HCV-G1 31 [26.7%]) were included. The mean age was 50.4±10.7 years and 56.9% were males. In terms of steatosis grading using the NAS scoring system, 50% had steatosis grade 0, 26.7% grade 1, 14.7% grade 2, and 8.6% grade 3, while the overall staging of steatosis revealed that 43.1% had mild steatosis, 42.2% moderate, and 14.7% severe. Gamma-glutamyl transpeptidase (GGT), platelet count, body mass index (BMI), cholesterol level, presence of hyperlipidemia, liver histology stage, and grade were significantly correlated with hepatic steatosis in one or more of the statistical analyses. Twenty-two out of 55 patients (40.0%) had an SVR in the mild steatosis group, compared to 52.7% in the moderate group and 7.3% in the severe group (P=0.03). The HCV genotype did not correlate with steatosis or SVR. CONCLUSION: Our study confirms the high prevalence of steatosis in HCV-G4 and HCV-G1 patients, but with no difference in the grade or score of steatosis between the two genotypes. The grade of steatosis correlates with GGT, platelet count, and BMI, while the NAS score of steatosis correlates with response to antiviral therapy.
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Antivirais/uso terapêutico , Fígado Gorduroso/epidemiologia , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Biópsia , Índice de Massa Corporal , Diabetes Mellitus/epidemiologia , Feminino , Genótipo , Hepacivirus/genética , Humanos , Hiperlipidemias/epidemiologia , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Prevalência , Proteínas Recombinantes , Estudos Retrospectivos , Arábia Saudita/epidemiologia , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Surveys indicate that up to 90% of general surgeons and gynecologists use monopolar radiofrequency during laparoscopy and 18% have experienced visceral burns. Monopolar electrosurgery compared with other energy sources is associated with unique characteristics and inherent risks and complications caused by inadvertent direct or capacitive coupling or insulation failure of instruments. These dangers become particularly important with the reemergence of single-port laparoscopy, which requires close proximity and crossing of multiple intraabdominal instruments outside the surgeon's field of view. STUDY OBJECTIVES: To determine the effects of monopolar electrosurgery on various tissues/organs during simulated single-port laparoscopic surgery in vitro and in vivo. DESIGN: Simulation in a dry laboratory with fresh sheep liver, pig bowel and bowel in an anesthetized dog (Canadian Classification II-3). SETTING: University-affiliated teaching hospital and animal facilities. MEASUREMENTS AND MAIN RESULTS: We used Valleylab Force 2 and FX electrosurgical generators at clinically used power outputs of 40 to 60 watts, and both high- and low-voltage (coagulation and cut) waveforms and commercially-available single-port devices. The effect on tissue was recorded by pictures and video camera and graded visually and histologically with hematoxylin and eosin stains. During activation of any standard monopolar laparoscopic instrument (scissors, coagulating electrode, etc), capacitive coupled currents resulting in visible tissue burn (blanching) caused by other adjacent cold instrument (graspers, etc) including metallic suction-irrigation cannulas and the laparoscope itself were noted. Histopathologic study confirmed transmural thermal damage extending to the mucosa of small bowel, even in the presence of mild serosa blanching. With prolonged activation of the electrosurgical generator, the capacitive coupled corona discharge burned the insulation and caused rapid insulation breakdown of the electrode instrument resulting in direct coupling (sparking, arcing) to adjacent cold instruments and more severe burning to the contacted tissue/organ. CONCLUSIONS: During single-port laparoscopy and use of monopolar radiofrequency, the proximity and crossing of multiple instruments generate capacitive or direct coupled currents, which may cause visceral burns.
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Queimaduras por Corrente Elétrica/etiologia , Eletrocirurgia/efeitos adversos , Intestinos/lesões , Intestinos/cirurgia , Laparoscopia/efeitos adversos , Animais , Cães , Ovinos , SuínosRESUMO
The aim of this work was to study the ability of beta-cyclodextrin (beta-CD) or hydroxypropyl beta-cyclodextrin (HP-beta-CD) to ameliorate the induction of gastric ulcers by a nonsteroidal anti-inflammatory drug, indomethacin or piroxicam, in rats exposed to restraint and hypothermic stress at 4 degrees C. Using oral gavage, rats fasted for 72 h were administered the equivalent of a 100 mg/kg dose of the assigned drug, alone or with the designated cyclodextrin (CD). The rats were placed in suitable rodent restrainers and then placed inside a ventilated refrigerator maintained at a temperature of 4 degrees C. Six hours later, each animal was removed, anaesthetized with ether, and the abdomen opened. Each stomach was removed, opened along the greater curvature and gently rinsed with isotonic saline solution. The induced gastric ulcers were examined and assessed with the help of a 10x binocular magnifier. Pronounced and marked gastric ulceration with complete loss of the mucosa, extensive deposition of fibrin and dense neutrophilic infiltrate were observed in rats treated with each of the drugs alone. Treatment with indomethacin or piroxicam alone induced ulcer indices of 26 +/- 2.3 or 14 +/- 1.8, respectively. However, beta-CD and HP-beta-CD each significantly suppressed ulceration due to restraint and cold stress. Rats treated with indomethacin or piroxicam in the presence of either beta-CD or HP-beta-CD exhibited normal tissues. Therefore, beta-CD and HP-beta-CD act as protective agents against gastrointestinal disorders produced by restraint and cold stress, even with the added stress from administration of either indomethacin or piroxicam.
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Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/química , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , beta-Ciclodextrinas/química , 2-Hidroxipropil-beta-Ciclodextrina , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Indometacina/efeitos adversos , Indometacina/química , Indometacina/uso terapêutico , Masculino , Piroxicam/efeitos adversos , Piroxicam/química , Piroxicam/uso terapêutico , Ratos , Ratos WistarRESUMO
In the present investigation, an ethanol extract of celery [Apium graveolens L. (Apiaceae/Umbelliferae)], at doses of 250 and 500 mg/kg body weight, was evaluated for antigastric ulcer activity using various experimental gastric ulcer models in rats. Ulcers were induced by indomethacin, cytodestructive agents (80% ethanol, 0.2 M NaOH and 25% NaCl) and cold restraint stress. Gastric secretory studies were undertaken by using pylorus ligation (Shay rat model). In addition to gastric wall mucus (GWM), non-protein sulfhydryl (NP-SH) and malondialdehyde (MDA) were also estimated in gastric tissues after 80% ethanol treatment. Pretreatment of celery extract produced dose-dependent reduction in all experimentally induced gastric lesions. Ethanol (80%) decreased the levels of GWM, NP-SH and increase in MDA concentration in gastric tissue. Celery extract showed the ability to significantly replenish the ethanol-induced depleted levels of GWM and gastric mucosal NP-SH. The gastric mucosal MDA level was also significantly lowered in extract pretreated rats. The celery extract showed stomach protection against the models used for ulcerogenesis. Results were further confirmed by using histopathological assessment. The phytochemical screening showed the presence of various chemical constituents such as flavonoids, tannins, volatile oils, alkaloids, sterols and/or triterpenes. Acute toxicity test revealed no deleterious or toxic symptoms or mortality over a period of 14 days. However, the LD(50) was found to be 7.55 g/kg, and showed a large margin of safety. The results suggest that Apium graveolens extract significantly protects the gastric mucosa and suppresses the basal gastric secretion in rats, possibly through its antioxidant potential.
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Antiulcerosos/uso terapêutico , Apium , Citoproteção/efeitos dos fármacos , Suco Gástrico/metabolismo , Fitoterapia , Extratos Vegetais/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Animais , Antiulcerosos/farmacologia , Antiulcerosos/toxicidade , Apium/toxicidade , Avaliação Pré-Clínica de Medicamentos , Feminino , Ácido Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Masculino , Malondialdeído/análise , Muco/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Distribuição Aleatória , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismoRESUMO
The causes of dysphonia or hoarseness are numerous and can be classified as functional or organic. The report will highlight the clinical presentation, histopathological features and management plan of laryngeal epidermal inclusion cysts (EICs). Laryngeal EICs are rare. The epidermal and dermoid cysts represent only 0.01% of oral cavity cysts. Their clinical presentation varies from a completely asymptomatic presentation to dysphonia for years. This current report represents a case of a 34-year-old female who presented with 2-year history of dysphonia, which was caused by a unilateral laryngeal EIC.
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Becker's melanosis (BM) is an uncommon cutaneous hamartoma. The classical descriptionof the lesion is of a macular, pigmented patch found on the upper trunk, with onset at or around adolescence. The aim of this study is to describe the clinicopathologic features of cases of BM which do not fit this typical description. Biopsy registry and laser clinic records from 2000-2006 at the authors' institution were searched for cases with a diagnosis or differential diagnosis of BM. A chart review was then undertaken to record clinical data and histological features of each case. Eleven cases which fit criteria for inclusion in the study were identified. The authors found that these eleven cases could all be described as BM with atypical features but were still clearly within the spectrum of this condition. Contrary to widely held belief, cases of Becker's melanosis with atypical features are not uncommon and might be under-reported.
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Hamartoma/patologia , Melanose/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Hamartoma/diagnóstico , Humanos , Lactente , Recém-Nascido , Masculino , Melanose/diagnóstico , Estudos Retrospectivos , Adulto JovemRESUMO
'Marjoram,' Origanum majorana L., a culinary aromatic medicinal herb is known to possess various therapeutic properties. We evaluated the antiulcerogenic activity of the ethanol extract in hypothermic restraint stress-, indomethacin-, necrotizing agents- (80% ethanol, 25% NaCl and 0.2 M NaOH) induced ulcers and basal gastric acid secretion using pylorus ligated Shay rat-model. Marjoram at doses of 250 and 500 mg/kg of body weight, significantly decreased the incidence of ulcers, basal gastric secretion and acid output. Furthermore, the extract replenished the ethanol-induced depleted gastric wall mucus and nonprotein sulfhydryls (NP-SH) contents and significantly lowered the increase in the concentration of malondialdehyde (MDA). Ulcer preventing potential was further confirmed by histopathological assessment. An acute toxicity test showed a large margin of safety of the extract in mice. The phytochemical screening of aerial parts of marjoram revealed the presence of volatile oil, flavonoids, tannins, sterols and/or triterpenes.
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Medicamentos de Ervas Chinesas/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Origanum/química , Úlcera Gástrica/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/toxicidade , Antioxidantes/farmacologia , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/toxicidade , Feminino , Ácido Gástrico/metabolismo , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Indometacina/toxicidade , Masculino , Malondialdeído/metabolismo , Camundongos , Óleos Voláteis/análise , Óleos Voláteis/farmacologia , Fitosteróis/análise , Fitosteróis/farmacologia , Ratos , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Compostos de Sulfidrila/metabolismo , Taninos/análise , Taninos/farmacologia , Triterpenos/análise , Triterpenos/farmacologiaRESUMO
Schistosoma is a parasitic infection that affects many people worldwide. However, pulmonary Schistosomiasis is very rare entity which defined as pulmonary involvement develops in persons living or travelling in endemic areas. We report a rare case of 23-year-old Yamani patient admitted as an emergency with a 1-week history of productive cough, hemoptysis, and chest pain. Chest X-ray and computed tomography scan showed right upper lobe peripheral abscess cavity. All routine blood investigations and interventions such as bronchoscopy and bronchoalveolar lavage failed to confirm the diagnosis. However, he underwent right thoracoscopy and excision of this abscess, which unexpectedly showed in the histopathology of the resected specimen Schistosoma parasite infection.
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Individuals with Lynch syndrome (LS) have germline variants in DNA mismatch repair (MMR) genes that confer a greatly increased risk of colorectal cancer (CRC), often at a young age. Identification of these individuals has been shown to increase their survival through improved surveillance. We previously identified 33 high risk cases for LS in the Saudi population by screening for microsatellite instability (MSI) in the tumor DNA of 284 young CRC patients. The aim of the present study was to identify MMR gene variants in this cohort of patients. Peripheral blood DNA was obtained from 13 individuals who were at high risk of LS due to positive MSI status and young age (<60 years at diagnosis). Next generation sequencing, Sanger sequencing and Multiplex Ligation-dependent Probe Amplification were used to screen for germline variants in the MLH1, MSH2, MSH6 and PMS2 MMR genes. These were cross-referenced against several variant databases, including the International Society for Gastrointestinal Hereditary Tumors Incorporated database. Variants with pathogenic or likely pathogenic significance were identified in 8 of the 13 high risk cases (62%), comprising 4 in MLH1 and 4 in MSH2. All carriers had a positive family history for CRC or endometrial cancer. Next generation sequencing is an effective strategy for identifying young CRC patients who are at high risk of LS because of positive MSI status. We estimate that 7% of CRC patients aged <60 years in Saudi Arabia are due to LS, potentially involving around 50 new cases per year.
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Biomarcadores Tumorais/genética , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Detecção Precoce de Câncer/métodos , Predisposição Genética para Doença , Instabilidade de Microssatélites , Adulto , Estudos de Coortes , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Reparo de Erro de Pareamento de DNA/genética , Feminino , Testes Genéticos/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL/genética , Proteína 2 Homóloga a MutS/genética , Arábia Saudita/epidemiologiaRESUMO
OBJECTIVE: To identify the most common liver pathologies seen in our center, to find the prevalence of advanced fibrosis and cirrhosis in patients with chronic hepatitis B and C, and to correlate the histological and laboratory features of the most common diseases and compare between them. METHODS: Liver biopsy procedures performed in our Gastroenterology Unit at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia were traced from records between the years 1997-2003. Clinical, histopathological, and laboratory features were recorded. RESULTS: We identified 574 liver biopsies during the study period. Of the 502 included patients, males were 58.6%. The mean age of the patients was 43.5 years. Approximately half of the biopsies (49%) were performed for patients with hepatitis C, followed by hepatitis B, for which 17% of the biopsies were performed. Patients with hepatitis B were approximately 10 years younger than patients with hepatitis C (p = 0.01). They were 10% more likely to be males. In terms of fibrosis, only approximately 17% of patients with hepatitis B and 27% of patients with hepatitis C had advanced fibrosis. CONCLUSION: Most liver biopsies performed in our center are performed for patients with hepatitis C. Rates of advanced fibrosis in our series are significantly lower than what was previously reported in other studies.
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Biópsia , Hepatite B Crônica/epidemiologia , Hepatite C Crônica/epidemiologia , Hospitais Universitários , Cirrose Hepática/epidemiologia , Cirrose Hepática/patologia , Fígado/patologia , Adulto , Feminino , Hepatite B Crônica/patologia , Hepatite C Crônica/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Arábia Saudita/epidemiologiaRESUMO
Esophagitis in children is not uncommon, mostly due to gastro-esophageal reflux. Other conditions like eosinophilic and infective esophagitis need to be elucidated in differential diagnoses. Fungal orCandida esophagitisusually occurs in high risk children who are immune-compromised, malnourished, on steroid therapy or have uncontrolled diabetes mellitus. An eleven-year girl presented with uncontrolled type I diabetes mellitus and recurrent epigastric pain with vomiting. Her oral intake was satisfactory. There was no dysphagia and odynophagia. Physical examination was normal with good oral hygiene. Failure in responding to conventional medications led to endoscopic evaluation, which revealed white patches and esophageal inflammation and diagnosed as fungal esophagitis on histopathology. Although infective esophagitis is encountered sporadically in pediatric age group, but it should always be considered in high risk individuals and when conventional medication fails to resolve the symptoms.
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Candidíase/diagnóstico , Diabetes Mellitus Tipo 1/complicações , Esofagite/diagnóstico , Dor Abdominal/etiologia , Antifúngicos/uso terapêutico , Biópsia , Candida/classificação , Candida/isolamento & purificação , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Candidíase/patologia , Criança , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/patologia , Esofagite/complicações , Esofagite/microbiologia , Feminino , Fluconazol/uso terapêutico , Humanos , Insulina/administração & dosagem , Resultado do Tratamento , Vômito/etiologiaRESUMO
BACKGROUND: Lynch Syndrome (LS) is a familial cancer condition caused by germline mutations in DNA mismatch repair genes. Individuals with LS have a greatly increased risk of developing colorectal cancer (CRC) and it is therefore important to identify mutation carriers so they can undergo regular surveillance. Tumor DNA from LS patients characteristically shows microsatellite instability (MSI). Our aim here was to screen young CRC patients for MSI as a first step in the identification of unrecognized cases of LS in the Saudi population. MATERIALS AND METHODS: Archival tumor tissue was obtained from 284 CRC patients treated at 4 institutes in Dammam and Riyadh between 2006 and 2015 and aged less than 60 years at diagnosis. MSI screening was performed using the BAT-26 microsatellite marker and positive cases confirmed using the pentaplex MSI analysis system. Positive cases were screened for BRAF mutations to exclude sporadic CRC and were evaluated for loss of expression of 4 DNA mismatch repair proteins using immunohistochemistry. RESULTS: MSI was found in 33/284 (11.6%) cases, of which only one showed a BRAF mutation. Saudi MSI cases showed similar instability in the BAT-26 and BAT-25 markers to Australian MSI cases, but significantly lower frequencies of instability in 3 other microsatellite markers. CONCLUSIONS: MSI screening of young Saudi CRC patients reveals that approximately 1 in 9 are candidates for LS. Patients with MSI are strongly recommended to undergo genetic counselling and germline mutation testing for LS. Other affected family members can then be identified and offered regular surveillance for early detection of LS-associated cancers.
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Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias Colorretais/epidemiologia , Instabilidade de Microssatélites , Mutação/genética , Adulto , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo de Erro de Pareamento de DNA/genética , Enzimas Reparadoras do DNA/metabolismo , DNA de Neoplasias/genética , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prevalência , Prognóstico , Estudos Retrospectivos , Arábia Saudita/epidemiologiaRESUMO
The TP53-induced glycolysis and apoptosis regulator (TIGAR) is a p53 target gene known to regulate glycolysis by acting as fructose bis-phosphatase (FBPase) and modulate reactive oxygen species. TIGAR expression has been implicated in oncogenesis and progression of several human cancers. However, TIGAR expression is not known in various stages of colorectal cancer (CRC). There is an increase in the colorectal cancer incidence in Saudi Arabia. We sought to analyze TIGAR expression in this ethnic group. The aim of this study was to investigate the TIGAR expression in colorectal cancer (CRC) patients from Saudi Arabia. Tissue microarray (TMA) was constructed from 22 matched colorectal tumor tissues and adjacent normal tissues. TIGAR expression was examined in TMA slide using immunohistochemistry. TIGAR mRNA was determined in 14 matched tumor tissue and adjacent normal tissue. TIGAR protein expression was also examined in CRC tumor tissues and cell lines. Statistical analyses (t-test) were applied to evaluate the significance of TIGAR expression. TIGAR mRNA level was upregulated significantly in stage II (p<0.01) and stage III (p<0.05) when compared to adjacent normal tissue. Immunohistochemical studies revealed that TIGAR expression was increased in colorectal cancer. Strong TIGAR positive staining was found in 68% (15/22) of the tumor samples with nuclear localization. TIGAR staining was found to be significantly increased in early stage (stage I and II) CRC (p<0.05) and late stage (stage III and IV) CRC (p<0.01). TIGAR protein was also found to be highly expressed in stage II and III colorectal cancer tissues and CRC cell lines. These findings indicate that TIGAR is highly expressed at the mRNA and protein levels in colorectal cancer with prominent nuclear localization. TIGAR expression may be used as a bio-marker for detection of colorectal cancer and can be used as a target for developing therapeutics for the treatment of colorectal cancer.
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Apoptose/genética , Transformação Celular Neoplásica/genética , Neoplasias Colorretais/genética , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Reguladoras de Apoptose , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Células HT29 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Monoéster Fosfórico Hidrolases , RNA Mensageiro/biossíntese , Espécies Reativas de Oxigênio/metabolismo , Análise Serial de Tecidos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
Mucin overexpression has been implicated in the tumorigenesis and progression of colorectal carcinoma (CRC). However, data obtained on the prognostic importance of mucin expression in CRC is inconsistent. Due to lack of data on mucin expression and the increase in CRC incidence in Saudi Arabia, the aim of the present study was to analyze the mucin expression profile in patients with CRC in this ethnic group. The present study consisted of 22 patients that underwent surgery for CRC. Histopathological and immunohistochemical staining was performed on CRC tumor and adjacent normal tissues. A tissue microarray was prepared from the tumor and normal adjacent samples to investigate the mucin expression profile using immunohistochemistry. Formalin-fixed paraffin-embedded human colorectal cancer tissues were immunostained with mucin 1 (MUC1), mucin 2 (MUC2) and mucin 5AC (MUC5AC) antibodies. Associations between mucin expression and histopathological variables were evaluated. The present study indicated that MUC1 was highly expressed in early (stage I and II; P=0.0016) and late (stage III and IV; P<0.0001) stage CRC tissues compared to normal adjacent tissues. However, MUC2 expression was observed to be downregulated in early and late stage CRC tissues compared to normal and adjacent tissues. Furthermore, serum MUC1 levels were observed to be increased in early and late stage CRC. The present findings indicate that MUC1 expression was significantly higher in early and late stage CRC tissues and MUC2 was downregulated in CRC tissues compared with normal adjacent tissues, and serum MUC1 protein was significantly higher in CRC patients compared to control serum. In conclusion, during colorectal tumorigenesis the pattern of MUC1 and MUC2 expression is altered in Saudi Arabian patients with CRC compared with normal. A higher expression of MUC1 may be used as an independent biomarker in various stages of CRC tumors, which would aid in the early detection of CRC.
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Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with higher metastatic rate and both local and systemic recurrence compared to non-TNBC. The generation of reactive oxygen species (ROS) secondary to oxidative stress is associated with DNA damage, chromosomal degradation and alterations of both hypermethylation and hypomethylation of DNA. This study concerns differential methylation of promoter regions in specific groups of genes in TNBC and non-TNBC Saudi females in an effort to understand whether epigenetic events might be involved in breast carcinogenesis, and whether they might be used as markers for Saudi BCs. Methylation of glutathione S-transferase P1 (GSTP1), T-cadherin (CDH13), Paired box protein 5 (PAX5), death associated protein kinase (DAPK), twist-related protein (TWIST), DNA-binding protein inhibitor (ID4), High In Normal-1 (HIN-1), cyclin-dependent kinase inhibitor 2A (p16), cyclin D2 and retinoic acid receptor-ß (RARß1) genes was analyzed by methylation specific polymerase chain reaction (MSP) in 200 archival formalin- fixed paraffin embedded BC tissues divided into 3 groups; benign breast tissues (20), TNBC (80) and non-TNBC (100). The relationships between methylation status, and clinical and pathological characteristics of patients and tumors were assessed. Higher frequencies of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 hypermethylation were found in TNBC than in non-TNBC. Hypermethylation of GSTP1, CDH13, ID4, DAPK, HIN-1 and PAX5 increased with tumor grade increasing. Other statistically significant correlations were identified with studied genes. Data from this study suggest that increased hypermethylation of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 genes in TNBC than in non-TNBC can act as useful biomarker for BCs in the Saudi population. The higher frequency of specific hypermethylated genes paralleling tumor grade, size and lymph node involvement suggests contributions to breast cancer initiation and progression.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma Ductal de Mama/genética , Metilação de DNA , Proteínas Quinases Associadas com Morte Celular/genética , Glutationa S-Transferase pi/genética , Proteínas Inibidoras de Diferenciação/genética , Fator de Transcrição PAX5/genética , Neoplasias de Mama Triplo Negativas/genética , Adulto , Carcinoma Ductal de Mama/patologia , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , Arábia Saudita , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
BACKGROUND: Secreted frizzled-related protein (SFRP) genes, new tumor suppressor genes, are negative regulators of the Wnt pathway whose alteration is associated with various tumors. In ovarian cancer, SFRPs genes promoter methylation can lead to gene inactivation. This study investigated mechanisms of SFRP and adenomatous polyposis coli (APC) genes silencing in ovarian cancer infected with high risk human papillomavirus. MATERIALS AND METHODS: DNA was extracted from 200 formalin-fixed paraffin-embedded ovarian cancer and their normal adjacent tissues (NAT) and DNA methylation was detected by methylation specific PCR (MSP). High risk human papillomavirus (HPV) was detected by nested PCR with consensus primers to amplify a broad spectrum of HPV genotypes. RESULTS: The percentages of SFRP and APC genes with methylation were significantly higher in ovarian cancer tissues infected with high risk HPV compared to NAT. The methylated studied genes were associated with suppression in their gene expression. CONCLUSION: This finding highlights the possible role of the high risk HPV virus in ovarian carcinogenesis or in facilitating cancer progression by suppression of SFRP and APC genes via DNA methylation.
Assuntos
Proteína da Polipose Adenomatosa do Colo/genética , Metilação de DNA , Glicoproteínas/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Proteínas de Membrana/genética , Neoplasias Ovarianas/genética , Infecções por Papillomavirus/genética , Proteínas Proto-Oncogênicas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/virologia , Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Prognóstico , Regiões Promotoras Genéticas , Fatores de Risco , Adulto JovemRESUMO
Several reports have described different lung lesions mimicking primary or metastatic neoplasms. In this paper, we describe the different features of two uncommon and benign lung lesions mimicking metastasis from a primary large bowel adenocarcinoma. Our patient is a 75-year old female with a history of invasive rectal adenocarcinoma. One month after her surgery, she started complaining of coughing and shortness of breath. Clear cell sugar tumor and minute meningothelial-like nodules had been found incidentally and simultaneously during her chest x-ray. The diagnosis had been made based on morphology and was supported by a positive staining to a panel of immunohistochemical stains including CD34, vimentin, HMB45, melan A and S100. An ultra-structural examination was also performed and confirmed the presence of melanosomes in sugar tumor. The coexistence of lung sugar tumor and minute pulmonary meningothelial-like nodules has never been reported in the literature and an awareness of these lesions is essential to correctly diagnose and stage patients.