1,068 research outputs found
The Transcriptomic and Genomic Analysis of Lamin A/C Expression in the Colon and in Colorectal Cancer
No full textLamins A and C, also known as A-type lamins, are type V nuclear intermediate filament proteins which form an interlacing meshwork of filaments subjacent to the inner nuclear membrane termed the nuclear lamina. A-type lamins have been implicated in DNA replication, gene transcription regulation, apoptosis, regulation of growth promoters and nuclear migration. Traditionally, expression of A-type lamins has been associated with differentiated cells. As such, mutations in A-type lamins have been associated with a diverse range of genetic diseases, including premature ageing syndromes and with increased proliferation, especially in tumours.
In colorectal cancer, expression of A-type lamins, have been shown to impart an adverse prognosis. In order to understand the underlying biological processes responsible for this adverse outcome in patients with colorectal cancer, I sought to clarify the expression profile of A-type lamins and their binding partners in normal colonic/rectal mucosa, prior to investigating the expression of A-type lamins in colorectal cancers. I used fresh tissue specimens obtained from patients with colorectal cancer for my experiments. A unique finding was the expression of lamin A in the putative stem cell niche of colonic / rectal mucosal crypts.
Further studies in the form of a microarray analysis, revealed a very complex picture of up regulation involving various signalling cascades in the cancer samples expressing A-type lamins. There was no evidence to suggest a direct involvement of A-type lamins influencing the Wnt signalling cascade, however, direct involvement of other signalling cascades, such as the IGF signalling cascade, Shh signalling cascade and TGF-β signalling cascades were noted. These signalling cascades were known to influence the Wnt signalling cascades and hence could play a crucial role in the pathogenesis of colorectal cancers expressing A-type lamins.
In addition to these important signalling cascades, other key genes involved in apoptosis, growth promoters, cell adhesion, stem cell regulation, oncogenes and tumour suppression, were noted to have a unique expression profile in the cancer sample expressing A-type lamins, not observed in the cancer sample lacking A-type lamin expression. These observations were suggestive of A-type lamins having a diverse range of actions via, as yet, undefined pathways. It would appear that A-type lamins were imparting a more motile, less adherent phenotype with stem cell like features in colorectal cancers expressing A-type lamins. This could explain the observed poor prognosis of patients with colorectal cancers expressing A-type lamins.
Creatine kinase brain (CKB), was also identified as an additional, potential, prognostic indicator in the Duke’s B group of patients with colorectal cancer expressing A-type lamins. This potential marker, in conjunction with A-type lamin expression could be used to identify a sub group of Duke’s B patients at high risk. Whether adjuvant therapy in this group would help improve their long term survival is unknown since no study has been done to assess this
Transcriptional regulation of PES1 expression by c-Jun in colon cancer.
No full textPescadillo is a nucleolar protein that has been suggested to be involved in embryonic development and ribosome biogenesis. Deregulated expression of human pescadillo (PES1) was described in some tumors, but its precise roles in tumorigenesis remains unclear. In this study, we generated three monoclonal antibodies recognizing PES1 with high specificity and sensitivity, with which PES1 expression in human colon cancer was analyzed immunohistochemically. Out of 265 colon cancer tissues, 89 (33.6%) showed positive PES1 expression, which was significantly higher than in non-cancerous tissues (P<0.001). Silencing of PES1 in colon cancer cells resulted in decreased proliferation, reduced growth of xenografts, and cell cycle arrest in G1 phase, indicating PES1 functions as an oncogene. We then explored the mechanism by which PES1 expression is controlled in human colon cancers and demonstrated that c-Jun, but not JunB, JunD, c-Fos, or mutant c-Jun, positively regulated PES1 promoter transcription activity. In addition, we mapped -274/-264 region of PES1 promoter as the c-Jun binding sequence, which was validated by chromatin immunoprecipitation and electrophoretic mobility shift assays. Moreover, we demonstrated a positive correlation between c-Jun and PES1 expression in colon cancer cells and colon cancer tissues. Upstream of c-Jun, it was revealed that c-Jun NH2-terminal kinases (JNK) is essential for controlling PES1 expression. Our study, in the first place, uncovers the oncogenic role of PES1 in colon cancer and elucidates the molecular mechanism directing PES1 expression
Energy balance and cancers
No full textEnergy balance results from the exact equilibrium between caloric intake and caloric expenditure. A caloric intake larger than caloric expenditure results in overweight, even obesity, but other determinants, like hormonal dysfunction and/or genetic traits may play a part in obesity syndrome. Obesity, and even overweight, have been recognized as risk factors for the development of cancers. Human epidemiological studies, which have tended to establish the nature of the relationship between energy balance and cancer, are summarized first, with the influence of the various factors which act both on obesity and on cancer risk. Among these factors are the macronutrients responsible for the caloric intake, and some lifestyle factors (physical activity, drinking habits and tobacco use). Second, the animal studies help to distinguish between different relevant factors, and to understand some of the underlying mechanisms. However, the insulin-resistance syndrome, which appears to underlie the relationship between obesity and hormone-dependent cancers, and possibly colon cancer, is only relevant to human physiology because hormonal alterations are part of it. Prevention of hyperinsulinemia, insulin resistance and the accompanying visceral obesity appears to be a major public health task for the prevention of cancers
The relation of fetal colon and rectum diameters with labor in healthy late-third trimester pregnancies
No full textInan, Cihan (Trakya Author)
Sayin, N. Cenk (Trakya Author)
Dolgun, Z. Nihal (Trakya Author)
Erzincan, Selen Gursoy (Trakya Author)
Uzun, Isil (Trakya Author)
Sutcu, Havva (Trakya Author)
Varol, Fusun (Trakya Author)Objective: To investigate the associations of fetal colon-rectum diameters with labor and fetal distress or meconium passage in healthy pregnancies in the late 3rd trimester. Study design: A total of 162 healthy, singleton pregnant women at >= 36(0/7) weeks who were in the latent phase of labor (n = 69) or those not in labor (n = 93, controls) at the time of ultrasound examination were enrolled. Fetal colon (ascending, transverse, descending, sigmoid) and rectum diameters, Doppler indices of materno-fetal vessels were measured. Data were analyzed according to the mode of delivery. Results: Fetal colon-rectum diameters were smaller in women in labor compared to controls (p = 0.001). Positive correlations were observed between fetal colon-rectum diameters and interval between ultrasound and labor onset in the control group except for those who had scheduled cesarean sections (C/S) (p = 0.001). Similar colon-rectum measurements were obtained in fetuses delivered via cesarean section due to fetal distress or to other indications (p>0.05). In women who had uterine contractions during ultrasound examination; later delivered by vaginal route, no association was observed between Apgar scores and colon-rectum diameters during latent-phase (p > 0.05), and also there were significant positive correlations between different segments of colon-rectum diameters and duration of neonatal meconium passage (p < 0.05). Conclusion: Fetal colon and rectum diameters are smaller during labor and the measurements tend to diminish as the labor approaches, but do not indicate fetal distress. (C) 2018 Elsevier By. All rights reserved
Cáncer de colon en el Hospital Nacional Luis N. Saenz - PNP del 2011 al 2012.
No full textEZQUERRA Bernardo, Juan Carlos. Cáncer de colon en el Hospital Nacional Luis N. Saenz - PNP del 2011 al 2012. Trabajo de Investigación (Especialista en Oncología Médica). Lima, Perú: Universidad Nacional Mayor de San Marcos, Facultad de Medicina Humana, Escuela de Post-Grado, 2013. 68 h.OBJETIVOS: Describir la experiencia obtenida en el manejo de pacientes con Cáncer de Colon en el HNLNS PNP.
METODOLOGÍA: Se revisó las historias de 81 pacientes diagnosticados de Cáncer de Colon (CC) cuyas edades fluctuaban ente los 38 y los 90 años, tratados en el departamento de Oncología y Hematología del HN LNS PNP entre 2011 y 2012.
RESULTADOS: La incidencia de CC en esta población cautiva es de 9 casos/100000 hab. Predomina en sexo masculino y entre los 45 y 75 años. El EC II fue relativamente el mas frecuente y se le relacionó clínicamente con rectorragia y alteración del habito defecatorio, mientras que en EC III y IV se relacionó con perdida ponderal. El adenocarcinoma es el tipo histológico mas frecuente y el grado histológico fue predominantemente 2 y 3. La incidencia de poliposis asociada fue del 10%, a predominio de Colon izquierdo y del tipo adenoma velloso. Fueron operados en EC II el 90,3%, en EC III el 73,3% y en EC IV el 36,8% y recibieron quimioterapia en EC II el 71%, en C III y IV el 100%. La supervivencia lograda después de 18 meses de seguimiento fue en EC II de 95%, EC III de 60% y en EC IV de 30%. La recurrencia fue mas frecuente en EC III y la progresión en EC IV. Tanto la recurrencia como la progresión afecto principalmente a hígado y peritoneo. Analizando el EC II según los criterios de riesgo se observó que los tres casos que recurrieron, pertenecen al grupo de alto riesgo, siendo los criterios mas frecuentes invasión linfovascular o peineural y la presencia de menos de 12 ganglios en la pieza operatoria.
CONCLUSIONES: El cáncer de Colon en la población de estudio tiene una incidencia similar a la del resto del país. La localización del tumor se correlaciona con la sintomatología y con el Estadío Clínico. Tanto el grado histológico alto, los estadíos Clínicos tardíos y la presencia de criterios de alto riesgo, en pacientes en EC II, están relacionados con mayor posibilidad de recurrencia y/o progresión, A pesar de que los tratamientos multidisciplinarios se basaron en la recomendación de guías internacionales, se sigue observando marcada diferencia en la Sobrevida de estos pacientes según los estadíos
Potassium channels in prostate and colonic cancer
No full textLarge conductance Ca2+-activated K+ channels in human prostate cancer
The KCNMA1 gene encoding the alpha-subunit of BK channels is amplified and BK channel expression is enhanced in late-stage, metastatic and hormone-refractory human prostate cancer tissues, whereas benign prostate tissues show only a weak expression of BK channels. PC-3 hormone-insensitive prostate cancer cells, but not hormone-sensitive prostate cancer cells (LNCaP) and benign prostate hyperplasia cells (BPH-1), show an amplification of the KCNMA1 gene and enhanced expression for BK channels. BK channel blockers and siRNA inhibit currents and growth of PC-3 cells. The BK channel activator 17beta-estradiol do not further stimulate currents or cell proliferation in PC-3 cells, indicating maximal channel activity and hormone insensitivity of the cells. On the contrary, 17beta-estradiol significantly enhances both currents and proliferation in LNCaP and BPH-1 cells. These results establish a role of BK channels for proliferation of prostate cancer cells. BK channel expression in late stage prostate cancer may be used as a prognostic marker and appears as a promising target for diagnosis and therapy of prostate cancer.
Potassium channels in colonic cancer
The role of K+ channels for proliferation of colonic cancer is shown in T84 human colonic carcinoma cells, mouse colorectal cancer models.
Abnormal colonic histology in cancer mouse models
At early stages of dimethylhydrazine (DMH) and N-methy-N-nitrosourea (MNU) treatment, histology demonstrated inflammation of the mouse colon. At later stage of carcinogen administration, changes of mucosal architecture and dysplasia were clearly observable. Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene are found in almost all human colonic cancers, and in familiar adenomatous polyposis. Heterozygous APCMin/+ mice developed multiple intestinal neoplasias.
Changes in Na+ and Cl- transport in colonic cancer mouse models.
Initial DMH or MNU treatment decreased Na+ and Cl- transport in the colon, which was also detected in the inflamed DSS-colon. Reduced Na+ absorption and Cl- secretion in the inflamed colon are probably a result of reduced Na+/K+ ATPase activity. In contrast to carcinogen treated mice, ENaC currents and expression are increased in the colon of APCMin/+ mice. Taken together, inflammation reduces Na+ absorption and promotes diarrhea, which is often observed during colitis. Conversely, colonic polyposis is often accompanied by stool irregularities. The increase in colonic Na+ absorption in APCMin/+ mice may contribute to dehydration of the feces and constipation.
Pathological expression of K+ channels in the colonic epithelium
We demonstrated a role of Kv and BK channels for development of colonic cancer both in vitro and in vivo. In T84 cells, we detected molecular and functional expression of several types of K+ channels, but only Kv support proliferation. These channels assist in regulation of intracellular pH and cellular Ca2+ signaling. We also found that Kv1.3, Kv1.5, Kv3.1 and members of the EAG-family are enhanced in the premalignant colon induced by carcinogens. In the APCMin/+ model, EAG and BK channels are increased in the proximal and distal colon, respectively.
Eag-1 and BK expression in human colorectal and prostate carcinomas
Expression of Eag-1 channels is detected in colonic crypts from patients with colorectal carcinomas, but in the healthy colons. The Eag-1 gene is amplified in human colonic cancers and is associated with reduced overall survival of the patients. This may serves as an early diagnostic and prognostic marker for cancer patients. Taken together, evidence is presented for a role of K+ channels during development and growth of prostate and colonic cancer. Kv channels, particularly Eag-1, and BK channels support proliferation and are likely to support progression of premalignant tissues towards cancer. Both BK and Eag-1 are markers of adverse prognosis in patients. The present data may therefore be useful in improving diagnosis, and treatment, and may have a prognostic value in patients with prostate and colonic cancer
MYU, a Target lncRNA for Wnt/c-Myc Signaling, Mediates Induction of CDK6 to Promote Cell Cycle Progression
No full textSummaryAberrant activation of Wnt/β-catenin signaling is a major driving force in colon cancer. Wnt/β-catenin signaling induces the expression of the transcription factor c-Myc, leading to cell proliferation and tumorigenesis. c-Myc regulates multiple biological processes through its ability to directly modulate gene expression. Here, we identify a direct target of c-Myc, termed MYU, and show that MYU is upregulated in most colon cancers and required for the tumorigenicity of colon cancer cells. Furthermore, we demonstrate that MYU associates with the RNA binding protein hnRNP-K to stabilize CDK6 expression and thereby promotes the G1-S transition of the cell cycle. These results suggest that the MYU/hnRNP-K/CDK6 pathway functions downstream of Wnt/c-Myc signaling and plays a critical role in the proliferation and tumorigenicity of colon cancer cells
Hemorroidectomia: análise de 36 casos.
No full textTrabalho de Conclusão de Curso - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Departamento de Clínica Cirúrgica, Curso de Medicina, Florianópolis, 198
Silica Surface Modification: in Search of More Hydrolytically Stable HPLC Stationary Phases
No full textPh.D.Abstract: A number of studies were done to develop hydrolytically stable HPLC stationary phases on superficially porous silica. The primary study used diazonium chemistry to generate a polymeric layer on the silica surface. Manipulations of synthetic conditions were performed to limit the polymer to a thin layer. Controlling the thickness of the polymer layer proved critical to chromatographic performance. Primary amine groups built into the polymer layer provide sites where further synthetic modification of the surface can be performed. Additionally, these amines were shown to influence the chromatographic properties of the phase via retention mapping. The polymer stationary phase exhibits reverse phase behavior, though highly organic mobile phases elicit some HILIC-like behavior. Under reverse phase conditions, the polymer was compared to a commercial phenyl column. The two columns showed similar retentivity for a diverse group of analytes. Lastly, the hydrolytic stability of the polymeric phases were tested via degradation in 0.5% TFA at 80°C. After 20 hours of exposure (2400 column volumes) optimized materials lost less than 10% of their initial retention. Additional studies sought to generate hydrolyticlly stable bonded phases through encapsulation of the silica support. Triethoxysilane was used to generate a self-assembled monolayer of type c silica. Despite numerous attempts to control the reaction, vertical polymerization of the silane could not be prevented. Catalytic hydrosilation of the type c silica using 4-vinylaniline yielded surface loadings of up to 6.4 µmol/m2. Encapsulation of the silica support with a carbonaceous layer was attempted by heating the polymer generated previously to 900°C under argon. Attempts to generate a carbonaceous layer on silica supports resulted in the formation of carbon black like materials as heating beyond the graphitic transition of the carbon was impossibe. Use of these materials as stationary phases results in high retentivity and poor peak shapes. At this time the materials generated are unfit for use in HPLC as a stationary phase.**To request an accessible version of the file(s) associated with this item, contact [email protected]. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.*
Le prime notizie dal/del Nuovo Mondo: Cristoforo Colombo e Americo Vespucci
No full textEn este texto se analizan la carta a Luis de Santangel de Cristobal Colon y la carta "Mundus novus" de Amérigo Vespucio, donde aparece cierta vision "eurocentrica" del Muevo Mundo
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