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BACKGROUND: Evidence indicates that most cases of colorectal carcinoma (CRC) develop from adenoma. A previous study demonstrated that mitochondrial Tu translation elongation factor (TUFM) might serve as an independent prognostic factor for colorectal cancer. However, the expression and function of TUFM in the normal-adenoma-cancer sequence have not been reported. In this study, we investigated the clinicopathologic significance of TUFM and p53 expression for the normal-adenoma-carcinoma sequence in colorectal epithelia and evaluated the roles of TUFM during the progression of colorectal tumors. METHODS: Paraffin-embedded specimens from 261 colorectal normal mucosa samples, 157 adenomas, and 104 early carcinomas were analyzed for TUFM and p53 expression by immunohistochemistry. RESULTS: Expression of TUFM and p53 was significantly increased during the colorectal normal-adenoma-carcinoma sequence (all P < 0.05). The expression of TUFM and p53 was associated with histologic type of adenomas (P = 0.028; P = 0.001) and grade of dysplasia (all P = 0.001). Expression of TUFM was positively correlated with that of p53 (r = 0.319, P = 0.001). CONCLUSIONS: Upregulated TUFM expression may play an important role in the transformation from colorectal normal mucosa to carcinoma through adenoma. Combined immunohistochemical detection of TUFM and p53 may be useful for evaluating the biological behavior of colorectal adenoma.
Assuntos
Adenoma/patologia , Colo/patologia , Neoplasias Colorretais/patologia , Proteínas Mitocondriais/metabolismo , Fator Tu de Elongação de Peptídeos/metabolismo , Reto/patologia , Proteína Supressora de Tumor p53/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Colo/metabolismo , Neoplasias Colorretais/metabolismo , Progressão da Doença , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Reto/metabolismoRESUMO
BACKGROUND: Gastric carcinoma (GC) has one of the highest mortality rates of cancer diseases and has a high incidence rate in China. Palliative chemotherapy is the main treatment for advanced gastric cancer. It is necessary to compare the effectiveness and toxicities of different regimens. This study explores the possibility of methylation of DNA damage repair genes serving as a prognostic and chemo-sensitive marker in human gastric cancer. METHODS: The methylation status of five DNA damage repair genes (CHFR, FANCF, MGMT, MLH1, and RASSF1A) was detected by nested methylation-specific PCR in 102 paraffin-embedded gastric cancer samples. Chi-square or Fisher's exact tests were used to evaluate the association of methylation status and clinic-pathological factors. The Kaplan-Meier method and Cox proportional hazards models were employed to analyze the association of methylation status and chemo-sensitivity. RESULTS: The results indicate that CHFR, MLH1, RASSF1A, MGMT, and FANCF were methylated in 34.3% (35/102), 21.6% (22/102), 12.7% (13/102), 9.8% (10/102), and 0% (0/102) of samples, respectively. No association was found between methylation of CHFR, MLH1, RASSF1A, MGMT, or FANCF with gender, age, tumor size, tumor differentiation, lymph node metastasis, and TNM stage. In docetaxel-treated gastric cancer patients, resistance to docetaxel was found in CHFR unmethylated patients by Cox proportional hazards model (HR 0.243, 95% CI, 0.069-0.859, p = 0.028), and overall survival is longer in the CHFR methylated group compared with the CHFR unmethylated group (log-rank, p = 0.036). In oxaliplatin-treated gastric cancer patients, resistance to oxaliplatin was found in MLH1 methylated patients (HR 2.988, 95% CI, 1.064-8.394, p = 0.038), and overall survival was longer in the MLH1 unmethylated group compared with the MLH1 methylated group (log-rank, p = 0.046). CONCLUSIONS: CHFR is frequently methylated in human gastric cancer, and CHFR methylation may serve as a docetaxel-sensitive marker. MLH1 methylation was related to oxaliplatin resistance in gastric cancer patients.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas de Ciclo Celular/genética , Metilação de DNA , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Intestinais/genética , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Neoplasias Peritoneais/genética , Neoplasias Gástricas/genética , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Seguimentos , Humanos , Neoplasias Intestinais/tratamento farmacológico , Neoplasias Intestinais/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Proteínas de Ligação a Poli-ADP-Ribose , Reação em Cadeia da Polimerase , Prognóstico , Regiões Promotoras Genéticas/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Ubiquitina-Proteína LigasesRESUMO
Background/Objective: Cribriform-morular thyroid carcinoma (CMTC) was considered a variant of papillary thyroid carcinoma (PTC) but is a separate entity in the 2022 World Health Organization classification. CMTC has an association with familial adenomatous polyposis (FAP). Our objective is to report a case of CMTC who was subsequently diagnosed with FAP, to highlight these associated entities and implications for management. Case Report: A 15-year-old female with a history of iron-deficiency anemia and alpha-gal syndrome presented with several years of goiter and dysphagia. She also noted unintentional weight loss, abdominal pain, melena and hematochezia, and symptomatic anemia. Physical examination was significant for multiple thyroid nodules. Laboratory results revealed normal thyroid function and iron deficiency. Multiple nodules were visualized on thyroid ultrasound, and fine needle aspiration biopsy was consistent with PTC. Total thyroidectomy was performed with a revised diagnosis of multifocal CMTC, with administration of adjuvant radioactive iodine due to persistent disease. Genetic testing confirmed FAP and she was referred for upper endoscopy, colonoscopy, and an evaluation for colectomy. Discussion: There are no best practice guidelines for management of CMTC. Management of CMTC is guided by FAP status; sporadic cases can be managed with hemithyroidectomy, while FAP-associated cases are better managed with total thyroidectomy. Recurrence is usually managed with surgical resection. The decision to treat with adjuvant radioactive iodine is often extrapolated from management of classic PTC. Conclusion: Thyroid carcinoma in the setting of extensive family history of colorectal carcinoma should arouse suspicion for CMTC. Patients with CMTC should receive a referral for colonoscopy and genetic testing for FAP.
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OBJECTIVE: To explore the relationship between different tissue levels of polyunsaturated fatty acid (PUFA) and the clinicopathologic parameters in colorectal carcinoma (CRC) and evaluate their prognostic significance. METHODS: Fresh frozen malignant tissue was obtained from 82 colorectal cancer patients at PLA general Hospital from December 2010 to March 2011. The immunohistochemical results were obtained for vascular endothelial growth factor (VEGF), P53 and Ki-67. The relationship between the PUFA level and such clinicopathological profiles as age, gender, location, differentiation degree, TNM (tumor, node and metastasis) stage, VEGF, Ki-67 and P53 was analyzed. RESULTS: Tissue level of arachidonic acid (AA) in patients aged over 60 years (n = 44) was significantly lower than those under 60 years (n = 38) (0.12% ± 0.06% vs 0.17% ± 0.09%, P = 0.045). In patients with tumor size < 5 cm (n = 42), tissue level of EPA was significantly higher (0.29% ± 0.13% vs 0.20% ± 0.14%, P = 0.030) while ω-6/ω-3 PUFA lower (10.8 ± 2.6 vs 13.2 ± 6.4, P = 0.031). Significant statistical difference existed in tissue level of LA, AA/ω-3 PUFA in different differentiation degrees(P = 0.013, 0.027). Tissue level of linoleic acid(LA) in poorly differentiated tumor was the highest (19.9% ± 6.3%) while AA/ω-3 PUFA the lowest (4.1 ± 2.0, P < 0.05). Tissue level of LA was higher in VEGF-positive tumors than those in VEGF-negative counterparts(16.2% ± 3.7% vs 13.9% ± 2.7%, P = 0.009) while the ratios AA/ω-3 PUFA, AA/ω-6 PUFA, AA/LA in VEGF-positive tumors were lower than those in VEGF-negative counterparts (5.0 ± 1.8 vs 6.7 ± 3.3, 0.30 ± 0.09 vs 0.34 ± 0.09, 0.50 ± 0.21 vs 0.61 ± 0.21, P = 0.004, 0.038, 0.030) . In Ki-67 negative LA was highest (22.5% ± 10.1%, P = 0.048). No significant differences existed in the level of PUFA among the gender, the clinicopathological stage, lymph node metastasis and groups with differential expressions of P53 (all P > 0.05). CONCLUSIONS: The tissue levels of PUFA are somewhat correlated with the clinicopathologic parameters of CRC. And the prognosis of CRC may be evaluated through the test of PUFA.
Assuntos
Ácido Araquidônico/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Proteína Supressora de Tumor p53/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: The relationship between the expression of CD133 and fragile histidine triad (FHIT) or prognosis in Chinese colorectal adenocarcinoma is unknown and needs to be explored. MATERIAL AND METHODS: The samples of colorectal adenocarcinoma from 200 Chinese patients with follow-up were analyzed for the expression of CD133 and FHIT proteins by immunohistochemical method. RESULTS: CD133 was highly expressed in up to 42.0%(84/200) of this group of colorectal adenocarcinomas. The expression of CD133 was significantly higher in carcinoma than in normal (P=0.0001) and in adenomatous mucosas (P=0.004). CD133 positively corresponds to histological grade, clinical stage, regional lymphatic metastasis, and distant metastasis (all P<0.05). The mean overall survival time was shorter in patients with CD133 high expression than in those with CD133 low expression (P00.0001). The expression of CD133 was inversely correlative with that of FHIT (r=-0.464, P=0.0001) in colorectal adenocarcinoma. CD133 was an independent prognostic factor (P=0.0001). CONCLUSIONS: The expression of CD133 may be inversely correlated with the expression of FHIT. It is suggested that CD133 may play an important role in the evolution of colorectal adenocarcinoma and be considered as a potential marker for the prognosis.
Assuntos
Hidrolases Anidrido Ácido/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Antígenos CD/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Glicoproteínas/metabolismo , Proteínas de Neoplasias/metabolismo , Peptídeos/metabolismo , Antígeno AC133 , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Adulto JovemRESUMO
Transplant-transmitted malignances are rare but devastating events. Primary brain tumors are the least common among reported donor-derived malignancies. We report a case of donor-transmitted pineoblastoma, a PNET, in a two-yr-old male recipient, who presented with a rapidly growing mass in the right mandible, four months after multiple visceral organ transplantation. The recipient had liver, pancreas, and small bowel transplants because of end-stage liver failure and short gut syndrome, which was secondary to large bowel resection for management of gastroschisis complicated by intestinal volvulus. The donor autopsy results became available seven wk after transplantation, which found a pineoblastoma with meningeal spread. Evaluation of eyes, adrenal glands, bone marrow, and other organs did not identify metastasis outside the CNS. A biopsy of the recipient's right mandibular mass revealed a malignant small round blue cell tumor with the immunohistochemistry profile of a PNET. Staging evaluation revealed the tumor in the right mandible with bone marrow involvement. Further investigation showed that recipient's tumor and donor's pineoblastoma shared the same immunophenotype and HLA type, suggesting the recipient's tumor is a donor-transmitted pineoblastoma. This is the first case report of donor-transmitted pineoblastoma post-organ transplant.
Assuntos
Neoplasias Encefálicas/patologia , Intestino Delgado/transplante , Transplante de Fígado/efeitos adversos , Neoplasias Mandibulares/etiologia , Transplante de Pâncreas/efeitos adversos , Glândula Pineal , Pinealoma/etiologia , Pré-Escolar , Evolução Fatal , Humanos , Masculino , Neoplasias Mandibulares/diagnóstico , Neoplasias Mandibulares/secundário , Pinealoma/diagnóstico , Pinealoma/secundário , Doadores de TecidosRESUMO
Hb H disease is rarely seen in individuals of African descent although α-thalassemia (α-thal) is common in this population. Usually α-thal is due either to heterozygosity or homozygosity for the -α(3.7) deletion in this population. We report Hb H disease that is caused by a frameshift mutation on one -α(3.7) allele in two unrelated individuals homozygous for the -α(3.7) deletion. These two cases highlight the importance of further investigation by direct sequencing of the -α(3.7) allele when the thalassemic phenotype does not correlate with the genotype obtained by initial molecular testing.
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Mutação da Fase de Leitura , Hemoglobina H/genética , Deleção de Sequência , Talassemia alfa/genética , Adolescente , Adulto , Negro ou Afro-Americano , Sequência de Bases , Análise Mutacional de DNA , Feminino , Homozigoto , Humanos , Masculino , alfa-Globinas/genéticaRESUMO
In the title mol-ecule, C(13)H(19)NO(4), except for two C atoms of the tert-butyl group, the non-H atoms are almost coplanar (r.m.s. deviation = 0.2542â Å). In the crystal, mol-ecules are linked into centrosymmetric dimers by two inter-molecular N-Hâ¯O hydrogen bonds, forming an R(2) (2)(10) ring motif.
RESUMO
In the title mol-ecule, C(16)H(25)NO(4), the non-H atoms, except for the two tert-butyl groups, are roughly planar (r.m.s. deviation of the non-H atoms = 0.086â Å). In the crystal, mol-ecules are linked into inversion dimers by pairs of N-Hâ¯O hydrogen bonds, forming R(2) (2)(10) ring motifs.
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MyoD regulates skeletal myogenesis. Since proteins associated with MyoD exert regulatory functions, their identification is expected to contribute important insights into the mechanisms governing gene expression in skeletal muscle. We have found that the RNA helicases p68/p72 are MyoD-associated proteins and that the noncoding RNA SRA also immunoprecipitates with MyoD. In vitro and in vivo experiments indicated that both p68/p72 and SRA are coactivators of MyoD. RNA interference toward either p68/p72 or SRA prevented proper activation of muscle gene expression and cell differentiation. Unexpectedly, reducing the levels of p68/p72 proteins impaired recruitment of the TATA binding protein TBP; RNA polymerase II; and the catalytic subunit of the ATPase SWI/SNF complex, Brg-1, and hindered chromatin remodeling. These findings reveal that p68/p72 play a critical role in promoting the assembly of proteins required for the formation of the transcription initiation complex and chromatin remodeling.
Assuntos
Diferenciação Celular/fisiologia , Músculo Esquelético/fisiologia , Proteína MyoD/metabolismo , RNA Helicases/metabolismo , RNA não Traduzido/metabolismo , Sequência de Aminoácidos , Células HeLa , Humanos , Dados de Sequência Molecular , Músculo Esquelético/citologia , Proteína MyoD/genética , RNA Helicases/química , Homologia de Sequência de AminoácidosRESUMO
Currently, CD133 is one of the best markers to characterize cancer stem cells and Her-1 is reported as an important marker for the prognosis of triple-negative breast cancer. To investigate the relationship between the expression of CD133 and Her-1 and clinicopathology as well as prognosis in triple-negative breast cancer, 67 cases of triple-negative invasive ductal breast carcinoma taken from 422 patients with breast cancer were analyzed by immunohistochemistry and clinicopathology with follow-up. The CD133 and Her-1 were expressed as positive in 43.3% (29/67) and 53.7% (36/67) of patients, respectively. The expression of CD133 corresponded to tumor size (P = 0.022), clinical stage (P = 0.001) and lymphatic metastasis (P = 0.001), but not to age and histological grade. By Kaplan-Meier analysis the expression of CD133 was correlative with overall survival (OS) (log rank = 9.346, P = 0.002) and disease free survival (DFS) (log rank = 38.840, P = 0.0001) time of breast cancer patients. The expression of Her-1 was corresponding to tumor size (P = 0.031), clinical stage (P = 0.005) and lymphatic metastasis (P = 0.002), but not to age and histological grade. By Kaplan-Meier analysis the expression of Her-1 was correlative with overall survival (OS) (log rank = 7.998, P = 0.005) and DFS (log rank = 4.227, P = 0.040) time of patients with cancer. It is concluded that the expression of CD133 and Her-1 may be correlative with prognosis in triple-negative breast cancer.
Assuntos
Antígenos CD/metabolismo , Biomarcadores Tumorais/análise , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Receptores ErbB/metabolismo , Glicoproteínas/metabolismo , Peptídeos/metabolismo , Antígeno AC133 , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismoRESUMO
OBJECTIVE: Primary peritoneal high-grade serous carcinoma is thought to arise from the peritoneum, but recent data suggest that the fallopian tube may be an occult source of many of these tumors. This study was performed to evaluate this hypothesis in an unselected series of cases. METHODS: Fallopian tubes from 51 consecutive cases meeting the GOG criteria for primary peritoneal high-grade serous carcinoma, FIGO stages II-IV, were analyzed. RESULTS: Serous tubal intraepithelial carcinoma (STIC) was identified in 19 patients (37%). When the fimbriae were examined, STIC was identified in 46%, and when all tubal tissue was examined, 56%. STIC was confined to the fimbriae in 53%, involved fimbriae and nonfimbrial mucosa in 20%, and was confined to nonfimbrial mucosa in 20%. Patients with STIC were significantly older than those without STIC (75 years vs. 67 years, respectively; p=0.007). Patients with STIC were significantly more likely to have FIGO stage IV disease as compared to those without STIC (42% vs. 12.5%, respectively; p=0.037). CONCLUSIONS: At least half the cases of primary peritoneal high-grade serous carcinoma are associated with intraepithelial carcinoma of the fallopian tube, usually involving the fimbriae. These findings support the view that, like "primary ovarian carcinoma," what has been traditionally classified as "primary peritoneal carcinoma" is probably derived from occult high-grade serous carcinoma in the fallopian tube. These findings have important implications for ultrasound screening trials for ovarian cancer which are based on the assumption that an enlarged ovary is a very early manifestation of disease.
Assuntos
Carcinoma in Situ/patologia , Cistadenocarcinoma Seroso/patologia , Neoplasias das Tubas Uterinas/patologia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Idoso , Feminino , Humanos , Metástase Neoplásica , Estadiamento de NeoplasiasRESUMO
In the title mol-ecule, C(8)H(11)NO(2), the r.m.s. deviation of non-H atoms from their best plane is 0.031â Å. Mol-ecules are connected via a pair of N-Hâ¯O hydrogen bonds into a centrosymmetric dimer.
RESUMO
In the title compound, C(16)H(18)N(4)O(3)·2H(2)O, the dihedral angle between the pyrrole and pyridine rings in the hydrazone mol-ecule is 7.12â (3)°. In the crystal structure, inter-molecular N-Hâ¯O, O-Hâ¯N and O-Hâ¯O hydrogen bonds link the hydrazone and water mol-ecules into double layers parallel to (101). The crystal packing exhibits weak π-π inter-actions between the pyrrole and pyridine rings of neighbouring hydrazone mol-ecules [centroid-centroid distance = 3.777â (3)â Å]. The crystal studied was a non-merohedral twin, the refined ratio of twin domains being 0.73â (3):0.27â (3).
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To explore the expression of leukemia-related protein 16 (LRP16) in invasive ductal breast carcinoma and analyze its correlation with clinicopathological feature and prognosis, immunohistochemistry was performed on 100 cases of invasive ductal breast carcinoma. Medical records were reviewed and clinicopathological analysis was performed. Leukemia-related protein 16 expression was detected in 33 of 100 cases (33%) of the invasive ductal breast carcinoma. Expression of LRP16 in carcinoma was obviously higher than that in normal breast tissue. LRP16 protein expression was found in 27.6% (21/76) of carcinoma at stage I and II, and 50.0% (12/24) of carcinoma at stage III and IV. LRP16 expression was found correlative with metastasis in the axillary lymph node (P = 0.001), stage (P = 0.042), estrogen receptor (ER) expression (P = 0.001), fragile histidine triad (FHIT) expression (P = 0.015) and CD133 expression (P = 0.038), but not with grade (P = 0.543), tumor size (P = 0.263), age (P = 0.840), menopause (P = 0.701) and HER-2 gene amplification (P = 0.463). The difference of the mean disease free survival (DFS) time between cancer patients with LRP16 expression (43.7 months) and those without (77.7 months) was statistically significant (Log rank = 9.989, P = 0.002). The difference of the mean overall survival (OS) time between cancer patients with LRP16 expression (50.0 months) and those without (120.0 months) was statistically significant (Log rank = 9.977, P = 0.002). Our finding suggests that expression of LRP16 protein is correlated with the stage, metastasis, prognosis and expression of ER, progesterone receptor, Ki-67, CD133 and FHIT in invasive ductal breast carcinoma.
Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Proteínas de Neoplasias/análise , Hidrolases Anidrido Ácido/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/química , Neoplasias da Mama/mortalidade , Hidrolases de Éster Carboxílico , Carcinoma Ductal de Mama/química , Carcinoma Ductal de Mama/mortalidade , Feminino , Genes erbB-2 , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Prognóstico , Receptores de Estrogênio/análiseRESUMO
A small 12-kb haplotype upstream of the AKT1 gene has been found to be associated with insulin resistance phenotypes. We sought to define the functional consequences of the three component polymorphic loci (rs1130214, rs10141867, rs33925946) on AKT1 and the upstream ZBTB42 gene. 5' RACE analysis of AKT1 transcripts in human skeletal muscle biopsies showed the predominant promoter to be 2.5 kb upstream of exon 2, and distinct from those promoters previously reported in rat. We then studied the effect of each of the three haplotype polymorphisms in transcriptional reporter assays in muscle, bone, and fat cell culture models, and found that each modulated enhancer and repressor activity are in a cell-specific and differentiation-specific manner. Our results in promoter assays are consistent with the human phenotype data; we found an anabolic effect on muscle and bone with increased mRNA expression of AKT1, and catabolic effect on fat with decreased expression. To test the hypothesis that rs10141867 affects transcription levels of the novel zinc finger protein ZBTB42 in vivo, we developed the allele-specific expression assay using Taqman technology to test for allelic differences within heterozygotes. The allele containing the derived polymorphism (haplotype H2) showed a 1.75-fold increase in expression in human skeletal muscle. Our data show a particularly complex effect of the component polymorphisms of a single haplotype on cells and tissues, suggesting that the coordination of different tissue-specific effects may have driven selection for the H2 haplotype. In light of the recent abundance of SNP association studies, our approach can serve as a method for exploring the biological function of polymorphisms that show significant genotype/phenotype associations.
Assuntos
Glucose/metabolismo , Síndrome Metabólica/genética , Proteínas Proto-Oncogênicas c-akt/genética , Sequência de Bases , Sequência Conservada , Técnicas Genéticas , Haplótipos , Homeostase , Humanos , Dados de Sequência Molecular , Músculo EsqueléticoRESUMO
BACKGROUND: The relationships between the expression of CD133, Ki-67 and prognosis in gastric adenocarcinoma are unknown and needs exploring. METHODS: The samples of gastric adenocarcinoma from 336 Chinese patients with follow-up were analyzed for CD133 and Ki-67 protein expressions by immunohistochemical method. RESULTS: CD133 was expressed in up to 57.4% (193/336) of this group of gastric carcinoma. The expression of CD133 was significantly higher in carcinoma than in normal (P = 0.0001) and dysplastic mucosas (P = 0.004). CD133 was positive corresponded with the tumour size, grade, infiltrative depth and clinical stage (all P < 0.05). The overall mean survival time of the patients with CD133 positive expression was shorter than that of patients with negative expression (P = 0.0001). The expression of CD133 has a positive correlation with that of Ki-67 (r = 0.188, P = 0.001) in gastric adenocarcinoma. CD133 was an independent prognostic indicator. (P = 0.0001). CONCLUSIONS: It is suggested that CD133 may play an important role in the evolution of gastric adenocarcinoma and should be considered as a potential marker for the prognosis.
Assuntos
Adenocarcinoma/imunologia , Antígenos CD/análise , Biomarcadores Tumorais/análise , Glicoproteínas/análise , Antígeno Ki-67/análise , Peptídeos/análise , Neoplasias Gástricas/imunologia , Antígeno AC133 , Adenocarcinoma/etnologia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , China , Feminino , Mucosa Gástrica/imunologia , Mucosa Gástrica/patologia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Medição de Risco , Neoplasias Gástricas/etnologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Fatores de Tempo , Regulação para Cima , Adulto JovemRESUMO
The asymmetric unit of the title compound, C(38)H(37)N(7)O(2), contains one half-mol-ecule, situated on a twofold rotational axis, in which one amino group is involved in intra-molecular N-Hâ¯O hydrogen bond and the two phenyl rings are twisted from the plane of pyrazolone ring by 26.69â (10) and 79.64â (8)°. The crystal packing exhibits no classical inter-molecular contacts.
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PURPOSE: To investigate the features of 18F-Fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in differentiating synchronous multiple primary lung cancers (sMPLC) from intropulmonary metastasis (IM). MATERIAL AND METHODS: Fifty-nine patients with two synchronous primary lung cancers were selected and 23 lung cancer patients with an additional solitary IM cancer were chosen as the control group between January 2009 and January 2019. Maximum standardized uptake values (SUVmax) on PET/CT was determined for each tumor. The SUVmax ratio between the two tumors was determined and receiver operating characteristic curve analysis was used to evaluate the diagnostic performance. RESULTS: The difference of SUVmax ratio between sMPLC (2.3 ± 1.6) and IM (1.5 ± 0.4) was significant, p < 0.01; the area under the curve of the SUVmax ratio was 0.78 with the optimal cutoff value 1.7 (sensitivity 62.7% and specificity 82.6%, p < 0.001). CONCLUSION: The SUVmax ratio between two tumors may be helpful in differentiating sMPLC from IM, independent studies with bigger size were needed to further confirm the findings.
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Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Metástase Linfática/diagnóstico por imagem , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias Primárias Múltiplas/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Idoso , Feminino , Fluordesoxiglucose F18 , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/normas , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Estudos RetrospectivosRESUMO
It has been controversial whether patients with hepatocellular carcinoma (HCC) should receive glucocorticoid therapy during chemotherapy. Recent studies have demonstrated that glucocorticoids increase the therapeutic sensitivity of tumors to some chemotherapeutic drugs, but the specific mechanism remains unclear. In the present study, dexamethasone (Dex) was used to treat HCC stem cells. The results demonstrated that Dex reduced stemness maintenance and selfrenewal of HCC stem cells, promoted epithelialtomesenchymal transition, inhibited migration and angiogenesis and, more importantly, increased cell sensitivity to the herpes simplex virus thymidine kinase/ganciclovir drug system in vitro and in vivo. Further mechanistic analyses demonstrated that Dex inhibited small ubiquitinlike modifier (SUMO) modification of several proteins in HCC stem cells, including hypoxiainducible factor (HIF)1α, an important hypoxia tolerance protein, and octamerbinding transcription factor 4 (Oct4), a crucial stemness maintenance protein. Inducing deSUMOylation of HIF1α and Oct4 reduced their accumulation in the nucleus, thereby inhibiting tumor angiogenesis and stemness maintenance. These findings provide a new perspective to the study of the mechanism underlying the antihepatocarcinogenesis effects of Dex. Due to the few side effects of glucocorticoids at low doses and their antiinflammatory effects, the appropriate combination of glucocorticoids and chemotherapeutic drugs is expected to improve the survival of HCC patients and their prognosis.