Molecular insight of the cAMP Responsive Element Binding Protein (CREB) in human breast cancer

CREB, cAMP responsive element binding protein is a positive regulatory protein transcriptional factor, for genes including aromatase, an enzyme that converts androgens to oestrogens, c-fos, tyrosine hydroxylase and neuropeptides like somatostatin and enkephalin. The expression of aromatase is highly aberrant in human breast cancer and has been implicated in the disease progression. Aromatase expression in breast cancer tissue is directed mainly by promoters 1.3 and II. CRE1 and CRE2 are essential for cAMP induced promoter II activity. CRE binding protein (CREB) bound to this element (CRE) and that this interaction was enhanced in the presence of cAMP. Despite the extensive work on aromatase, little information is available on the expression and role of CREB in human breast cancer. The aim of this study was to investigate the molecular impact of CREB family of proteins on the aggressive nature of breast cancer cells and to investigate the expression pattern in breast cancer tissues in relation to tumour histopathological grade, stage, nodal status and the clinical outcome of the patients. In this study we examined the expression of CREB1 and ATFs (Activating transcription factors) in breast cancer cell lines using RT-PCR, which allowed us to design the strategy of in vitro experiments. Ribozyme knockdown technology was used to target the expression of CREB1 in a breast cancer cell line MDA-MB-231. Knockdown of CREB1 using ribozyme transgenes resulted in decrease in in vitro cell growth and invasiveness in breast cancer cells. The results presented here demonstrate that the level of CREB-1 and ATFs in breast cancer patients was elevated. The study results presented here revealed a significant link between CREB and mortality, in that high levels are associated with shorter disease free survival and interestingly we found significantly low levels of ATFs in patients with poor prognosis, metastatic disease and nodal involvement. We conclude that the level of CREB-1 and ATFs are aberrantly expressed in human breast cancer which may be associated with disease progression in breast cancer patients and has significant bearing to the clinical outcome of the patients. Over-expression of aromatase in adipose tissue surrounding breast tumour could arise through increase in both CREB expression and CREB transcriptional activity. Inhibition of CREB activity could inhibit aromatase expression and hence decrease oestrogen production in breast tissue. An understanding of the molecular mechanisms of expression of CREB, together with aromatase between non-cancerous and cancerous breast tissue at both transcriptional and translational levels may help in the design of a therapy based on suppressing aromatase expression in breast cancer tissues

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Vertebral body hyperostosis as a presentation of Pott's disease: A report of two cases and literature review

Vertebral body tuberculosis has numerous forms of presentations. We present two patients of Pott′s disease, in whom vertebral body hyperostosis was the radiological presentation. Both the patients had massive hyperostosis of vertebral bodies leading to the obliteration of the spinal canal and neurological deficits. The first case had associated lupus vulgaris, while the second patient had milliary mottling of lungs and calcified bilateral psoas muscles. Surgical decompression, followed by full-dose chemotherapy, remains the hallmark of management of this disease

Choroid plexus papilloma of the fourth ventricle in a septuagenarian

Choroid plexus papillomas (CPP) are most commonly found in children and rarely in adult. A very few cases are reported in geriatric population. We present a case of 72-year-old man with posterior fossa lesion operated with provisional diagnosis of metastasis, but turn out to be CPP

Morbidity in breast cancer patients with sentinel node metastases undergoing delayed Axillary Lymph Node Dissection (ALND) compared with immediate ALND

Background Patients with sentinel lymph node (SLN) metastases need delayed completion axillary lymph node dissection (ALND) if intraoperative assessment of SLN is not employed. This study was designed to compare morbidity in patients undergoing complete ALND in the first (and only) operation versus those undergoing the two-step procedure (SLN biopsy followed by delayed completion ALND). Methods Secondary analysis of the Axillary Lymphatic Mapping Against Nodal Axillary Clearance (ALMANAC) randomized trial compared 83 patients with SLN metastases who proceeded to delayed completion ALND (two-step ALND) with 96 node-positive patients who underwent ALND as the only axillary procedure (one-step ALND). Outcome variables were assessed at baseline and at 3, 6, and 12 months after surgery. Results The 83 SLN-positive patients undergoing completion ALND were younger (p = 0.038) compared with the one-step ALND group. There was no difference in lymphedema, sensory loss, intercostobrachial (ICB) nerve division rates, impairment of shoulder movement, infection rate, or time to resumption of normal day-to-day activities after surgery between the two groups. Median axillary operative time for completion ALND in the two-step group was significantly higher than one-step ALND (33 min vs. 25 min, p = 0.004). The median hospital stay for the second surgery in the two-step group was similar to one-step ALND (6 days). The total median hospital stay (first and second surgery) was significantly higher for the two-stage procedure (10 vs. 6 days, p < 0.001). Conclusion A two-stage axillary node dissection procedure in patients with SLN metastases has similar arm morbidity to one-stage ALND. The second surgery is associated with increased axillary operative time and total hospital stay

Expression of transcription factor CREB1 in human breast cancer and its correlation with prognosis

It has been suggested that the cAMP responsive element-binding protein (CREB) may act as a transcription regulator of aromatase in breast cancer cells. However, there is little knowledge on the expression of CREB1 in human breast cancer and its clinical significance. The current study investigated the expression pattern of CREB1 in human breast cancer at the mRNA and protein level and correlated it with the clinical outcome. CREB1 staining was primarily seen in the nucleus of both normal and tumour cells. At the mRNA level, we found a significantly higher level of CREB1 in breast tumour tissues (n=120) as compared to non-neoplastic mammary tissues (n=33, p=0.0092). When compared between different histological types CREB1 expression was significantly higher in ductal carcinoma as compared to lobular and other breast carcinoma. Patients with a poor prognosis and with metastasis had a markedly raised level of CREB1 compared to patients who were disease free. In addition, node-positive tumours had higher levels of CREB1 than node-negative tumours (p=0.0018). Finally, patients with high levels of CREB1 had a significantly shorter disease-free survival [95.3 (68.4-122.3, 95% CI) months] compared with those with lower levels [133.9 (123.5-144.2) months, p=0.0193]. This study demonstrates that the level of CREB1 in breast cancer patients is elevated and is significantly raised in patients with a poor prognosis, metastatic disease and nodal involvement. We conclude that the level of CREB1 expression is aberrant in human breast cancer and is associated with disease progression in breast cancer patients

Factors affecting failed localisation and false-negative rates of sentinel node biopsy in breast cancer--results of the ALMANAC validation phase

BACKGROUND: Despite the widespread application of sentinel lymph node biopsy (SLNB) for early stage breast cancer, there is a wide variation in reported test performance characteristics. A major aim of this prospective multicentre validation study was to quantify detection and false-negative rates of SLNB and evaluate factors influencing them. METHODS: Eight-hundred and fourty-two patients with clinically node-negative breast cancer underwent SLNB according to a standardised protocol that used a combination of radiopharmaceutical 99mTc-albumin colloid and Patent Blue V dye. SLNB was followed by standard axillary treatment at the same operation in all patients. RESULTS: Sentinel lymph nodes (SLNs) were identified in 803 (96.1%) of 836 evaluable cases. The median number of SLNs removed per patient was 2 (range 1-9). There were 19 false negatives, resulting in a sensitivity of 263/282 (93.3%) and accuracy 782/803 (97.6%). SLNs were successfully identified by blue dye in 698 (85.6%), by isotope in 698 (85.6%), and by the combination of blue dye and isotope in 782 (96.0%) of 815 patients. Among 276 node positive patients, one or more positive SLNs were identified by blue dye in 251 (90.9%), by isotope in 246 (89.1%) and by the combination of blue dye and gamma probe in 258 (93.5%). Obesity, tumor location other than upper outer quadrant and non-visualisation of SLNs on the pre-operative lymphoscintiscan were significantly associated with failed localisation (p<0.001, p=0.008, p<0.001, respectively). The false-negative rate in patients with grade 3 tumors was 9.6%, compared with 4.7% in those with grade 2 tumors (p=0.022). The false-negative rate in patients who had one SLN harvested was 10.1%, compared with 1.1% in those who had multiple SLNs (three or more) removed (p=0.010). CONCLUSION: SLNB can accurately determine whether axillary metastases are present in patients with early stage breast cancer with clinically negative axillary nodes. Both success and accuracy of SLNB are optimised by the combined use of blue dye and isotope. SLNB success decreases with increasing body mass, tumor location other than the upper outer quadrant and non-visualisation of hot nodes on the pre-operative lymphoscintiscan. This study demonstrates reduction in the predictive value of a negative SLNB in grade 3 tumors

Preoperative diagnosis of allergic fungal sinusitis

Objectives/Hypothesis: Although the diagnosis of allergic fungal sinusitis is mainly based on characteristic histopathological findings, certain preoperative diagnostic criteria have been proposed. However, their usefulness in differentiating allergic fungal sinusitis from other sinus diseases is unknown. The objective of the study was to identify accurate preoperative diagnostic parameters for allergic fungal sinusitis. Study Design: Prospective, comparative study. Methods: Twenty consecutive cases of allergic fungal sinusitis were evaluated prospectively and compared with 16 cases of ethmoidal polyposis and 5 cases of invasive sinus aspergillosis, with regard to various clinical, radiological, and immunological parameters. All patients were categorized based on histopathological findings. Results: Nasal polyps were seen in all 20 cases of allergic fungal sinusitis, all 16 cases of ethmoidal polyposis, and 2 of 5 cases of invasive sinus aspergillosis. Computed tomography (CT) scan hyper-attenuation was seen in all 20 cases of allergic fungal sinusitis but also in 2 (13%) cases of ethmoidal polyposis and 2 (40%) cases of invasive sinus aspergillosis. Serum levels of specific anti-Aspergillus immunoglobulin E were elevated in 14 (70%) cases of allergic fungal sinusitis, 2 (13%) cases of ethmoidal polyposis, and 3 (60%) cases of invasive sinus aspergillosis. The combination of all three (ie, nasal polyps, CT scan hyper-attenuation, and elevated titers of anti-Aspergillus immunoglobulin) was not found in any case of ethmoidal polyposis or invasive sinus aspergillosis. This triad demonstrated a sensitivity of 70% and a specificity of 100% for the preoperative diagnosis of allergic fungal sinusitis. Conclusions: Nasal polyps, CT scan, and specific immunoglobulin E titers, when considered in combination, have a high preoperative diagnostic value in allergic fungal sinusitis. However, they should not be considered in isolation because considerable overlap occurs with invasive sinus aspergillosis and ethmoidal polyposis

Preparedness among dental professionals towards COVID-19 in India

Introduction:&nbsp;novel corona virus infection has become a public health crisis leading the world to a standstill including dentistry. However, since the dental services cannot be stopped for a long period it is important that dentist be fully prepared before resuming their services. Therefore, the current study was carried out for evaluating knowledge, attitude and practices (KAP) along with perceived barriers to practice dentistry during pandemic. Methods:&nbsp;this cross-sectional study was conducted through an online survey questionnaire on dentists of India. Dentists were enquired for demographics, KAP and perceived barriers regarding practicing dentistry during pandemic. The knowledge was assessed based on 16 items in true or false or multiple choice questions format getting score of 1 or 0. The attitude and practices by 8 items each, on 5-point Likert scale and 4 items perceived barriers were enquired. The differences between the median scores among demographic variables were determined by applying student's t-test and keeping level of significance at below 0.05. Results:&nbsp;out of 500 dentists who were approached through email, a total of 296 dentists returned the questionnaire (response rate, 59.2%) among which 22 questionnaires were incomplete and thus excluded making 274 as final study participants. Overall poor median scores of knowledge and practices were obtained whereas for attitude total median score was good. Median practice scores were significantly higher among female respondents (20(6)). Median knowledge and practice scores were significantly better in study participants with age &lt;40 years (6(4) and 19(5), respectively). Conclusion:&nbsp;with the recent claims of authorities that virus is going to stay in world for quite some time it is essential that dentists must be fully prepared before resuming their services and must attain proper awareness to limit the disease spread