Amyloid protein produced by B. cereus CR4 possesses bioflocculant activity and has potential application in microalgae harvest.

Bacillus cereus CR4 from the flocs of activated sludge was found to produce an extracellular bioflocculant, which was characterized as amyloid protein and demonstrated to have potential application in microalgae recovery. Cell surface amyloid production was demonstrated by fluorescence, confocal and scanning electron microscopy. Birefringence, spectral shift assay, TEM, FTIR and CD spectra confirmed the amyloid nature of the purified protein that demonstrated flocculation. The gene for amyloid protein of B. cereus CR4 was found to be related to tasA gene of amyloid protein produced by Bacillus subtilis. The results demonstrated that the amyloid protein produced by B. cereus CR4 possessed a novel bioflocculant activity which at pH below 4.5 reached to a maximum of 86.87%. The amyloid bioflocculant producing B. cereus CR4 has a potential in biotechnological application like Scenedesmus biomass recovery.

Complete excision with narrow margins provides equivalent local control to wider excision in breast conservation for invasive cancer.

Background: Society of Surgical Oncology and American Society for Radiation Oncology guidelines define clear margins in breast-conserving therapy (BCT) as 'no ink on tumour', in contrast to the attainment of margins of at least 1 mm widely practised in the UK. The primary aim of this study was to explore clinical, surgical and tumour-related factors associated with local recurrence after BCT, with a secondary aim of assessing the impact of margin re-excision on the risk of local recurrence. Methods: Patient demographics, surgical details, tumour characteristics and local recurrence were recorded for consecutive women with BCT undergoing surgery between January 1997 and January 2007. Margins were defined as clear (greater than 1 mm), close (less than 1 mm but no ink on tumour), reaches (ink on tumour) and clear after re-excision. Results: A total of 1045 women of median age 54 (range 18-86) years were studied. Median follow-up was 89 (range 4-196) months. Local recurrence occurred in 52 patients (5·0 per cent). Ink on tumour was associated with local recurrence (hazard ratio (HR) 4·86, 95 per cent c.i. 1·49 to 15·79; P = 0·009). Risk of local recurrence was the same for close and clear margins (HR 1·03, 0·40 to 2·62; P = 0·954). In women with involved margins, re-excision was still associated with an increased local recurrence risk (HR 2·50, 1·32 to 4·72; P = 0·005). Oestrogen receptor negativity increased risk (HR 2·28, 1·28 to 4·06; P = 0·005). Conclusion: Adequately excised margins, even when under 1 mm, provide equivalent outcomes to wider margins in BCT. Achieving complete excision at primary surgery achieves the lowest rates of local recurrence.

INTEND II randomized clinical trial of intraoperative duct endoscopy in pathological nipple discharge.

BACKGROUND: The majority of lesions resulting in pathological nipple discharge are benign. Conventional surgery is undirected and targeting the causative lesion by duct endoscopy may enable more accurate surgery with fewer complications. METHODS: Patients requiring microdochectomy and/or major duct excision were randomized to duct endoscopy or no duct endoscopy before surgery. Primary endpoints were successful visualization of the pathological lesion in patients randomized to duct endoscopy, and a comparison of the causative pathology between the two groups. The secondary endpoint was to compare the specimen size between groups. RESULTS: A total of 68 breasts were studied in 66 patients; there were 31 breasts in the duct endoscopy group and 37 in the no-endoscopy group. Median age was 49 (range 19-81) years. Follow-up was 5·4 (i.q.r. 3·3-8·9) years in the duct endoscopy group and 5·7 (3·1-9·0) years in no-endoscopy group. Duct endoscopy had a sensitivity of 80 (95 per cent c.i. 52 to 96) per cent, specificity of 71 (44 to 90) per cent, positive predictive value of 71 (44 to 90) per cent and negative predictive value of 80 (52 to 96) per cent in identifying any lesion. There was no difference in causative pathology between the groups. Median volume of the surgical resection specimen did not differ between groups. CONCLUSION: Diagnostic duct endoscopy is useful for identifying causative lesions of nipple discharge. Duct endoscopy did not influence the pathological yield of benign or malignant diagnoses nor surgical resection volumes. Registered as INTEND II in CancerHelp UK clinical trials database (https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-at-changes-inside-the-breast-ducts-of-women-who-have-nipple-discharge).

Physicochemical characterization of pectinase activity from Bacillus spp. and their accessory role in synergism with crude xylanase and commercial cellulase in enzyme cocktail mediated saccharification of agrowaste biomass.

AIM: The aim of this study was to evaluate the physicochemical properties of the crude pectinase activity from three Bacillus isolates of ruminant dung origin and study their synergism with crude xylanases from the same Bacillus spp. and a commercial cellulase to evaluate their accessory role in improved biomass saccharification. METHODS AND RESULTS: Pectinolytic crude culture filtrate obtained from three ruminant dung isolates, Bacillus safensis M35, Bacillus altitudinis R31 and Bacillus altitudinis J208, on crude pectin containing medium possessed polygalacturonate hydrolase, pectate lyase and pectin lyase activities. Studies regarding their stability under various temperature and pH conditions revealed their mild acidic to alkaline and mesophilic nature with enzyme activity falling within the pH range 6·0-9·0 and temperature range 30-60°C. The pectinase activity was categorized as endolytic as it brought about ~50% reduction in relative viscosity of pectic polymer within initial 10 min of incubation. Synergism of pectinase activity with crude xylanase activities and/or commercial cellulase was clearly demonstrated as ~1·6 to ~1·9-fold increase in agrowaste biomass saccharification was obtained confirming the role of pectinases as accessory enzymes. CONCLUSION: Synergism of the broad-spectrum endopectinase activity obtained from three Bacillus isolates with accessory crude xylanases from the same isolates and commercial cellulase enhanced the agrowaste saccharification and confirmed the accessory role of crude pectinase as they formed an efficient enzyme cocktail functioning in a contributive manner for improvement of agrowaste biomass saccharification. SIGNIFICANCE AND IMPACT OF THE STUDY: Mesophilic crude endopectinases obtained from Bacillus spp. isolated from ruminant dung possessed activity in broad pH and temperature ranges as well as broad substrate specificity. Moreover, their synergism with crude xylanase and Primfast® 200 cellulase demonstrated the potential to form efficient enzyme cocktail for application in plant biomass saccharification process.

Bioemulsifier (BE-AM1) produced by Solibacillus silvestris AM1 is a functional amyloid that modulates bacterial cell-surface properties.

A novel estuarine bacterial strain, Solibacillus silvestris AM1, produces an extracellular, thermostable and fibrous, glycoprotein bioemulsifier (BE-AM1). The amyloid nature of the bioemulsifier (BE-AM1) was confirmed by biophysical techniques (Congo red based polarization microscopy, ThioflavinS based fluorescent microscopy, fibrous arrangement in transmission electron microscopy and secondary structure measurement by FTIR and CD spectrum analysis). Cell-bound BE-AM1 production by S. silvestris AM1 during the mid-logarithmic phase of growth coincided with a decrease in cell surface hydrophobicity, and an increase in cell autoaggregation and biofilm formation. It was observed that the total interfacial interaction energy ([Formula: see text]) for the surface of the bioemulsifier producing S. silvestris AM1 and different derivatized surfaces of polystyrene (silanized and sulfonated) was found to support biofilm formation. This study has revealed that the BE-AM1, a bacterial bioemulsifier, is a functional amyloid and has a role in biofilm formation and cell surface modulation in S. silvestris AM1.

Microcosm-based interaction studies between members of two ecophysiological groups of bioemulsifier producer and a hydrocarbon degrader from the Indian intertidal zone.

Isolates were obtained from intertidal zone site samples from all five western and one eastern coastal states of India and were screened. These ecophysiological groups of aerobic, mesophilic, heterotrophic, sporulating, and bioemulsifier-producing bacteria were from Planococcaceae and Bacillaceae. This is the first report of bioemulsifier production by Sporosarcina spp., Lysinibacillus spp., B. thuringiensis, and B. flexus. In this group, Solibacillus silvestris AM1 was found to produce the highest emulsification activity (62.5 %EI) and the sample that yielded it was used to isolate the ecophysiological group of non-bioemulsifier-producing, hydrocarbon-degrading bacteria (belonging to Chromatiales and Bacillales). These yielded hitherto unreported degrader, Rheinheimera sp. CO6 which was selected for the interaction studies (in a microcosm) with bioemulsifier-producing S. silvestris AM1. The gas chromatographic study of these microcosm experiments revealed increased degradation of benzene, toluene, and xylene (BTX) and the growth of Rheinheimera sp. CO6 in the presence of bioemulsifier produced by S. silvestris AM1. Enhancement of the growth of S. silvestris AM1 in the presence of Rheinheimera sp. CO6 was observed possibly due to reduced toxicity of BTX suggesting mutualistic association between the two. This study elucidates the presence and interaction between enhancers and degraders in a hydrocarbon-contaminated intertidal zone and contributes to the knowledge during application of the two in remediation processes.

Xylanases of Bacillus spp. isolated from ruminant dung as potential accessory enzymes for agro-waste saccharification.

UNLABELLED: Polysaccharide hydrolase producing bacteria were isolated for biomass saccharification step in two-step bioethanol production. Xylanolytic bacteria were found to be common in ruminant dung. Seven Bacillus dung isolates exhibited high xylanolytic activity; three of which were identified as Bacillus safensis and four as Bacillus altitudinis, based on 16S rDNA and gyrB gene sequencing. Interestingly, comparison of activity profiles for B. safensis M35 and B. altitudinis R31 and J208 crude xylanases showed activity in similar temperature and pH ranges of 40-60 °C and 6·0-9·0, respectively, even though they were isolated from three different dung sources. Furthermore, 22-28% viscosity reduction of beechwood xylan substrate by all the three xylanases points towards their endo-acting nature. Endo-acting xylanases are envisaged as accessory enzymes which help expose the cellulose fibres for the subsequent action of the core enzyme cellulases. In this study, when supplemented to the commercial cellulase as a cocktail, the accessory role of the crude xylanases from the selected Bacillus strains was established as 1·3, 2·33 and 1·9 fold increase in saccharification of barley husk, sugarcane bagasse and wheat husk was achieved, respectively. SIGNIFICANCE AND IMPACT OF THE STUDY: The uncontrolled use of fossil fuels and concerns about its future availability, have invoked interest over unconventional alternative energy sources like solar, hydropower, geothermal, nuclear and biomass. Plants, being largest renewable biomass on earth, have received consideration as a source of biofuels. Ruminant dung isolates M35, R31 and J208 belonging to Bacillus sp. produces majorly endo-xylanase when induced with wheat bran. Such plant cell wall degrading endo-xylanases with broad pH optima and mesophilic nature can act as accessory enzymes with cellulases to enhance the saccharification of plant biomass in biofuel industries.

Residual proliferative cancer burden to predict long-term outcome following neoadjuvant chemotherapy.

BACKGROUND: The purpose of this study was (i) to test the hypothesis that combining Ki67 with residual cancer burden (RCB) following neoadjuvant chemotherapy, as the residual proliferative cancer burden (RPCB), provides significantly more prognostic information than either alone; (ii) to determine whether also integrating information on ER and grade improves prognostic power. PATIENTS AND METHODS: A total of 220 patients treated with neoadjuvant chemotherapy for primary breast cancer were included in the study. Analyses employed a Cox proportional hazard model. Prognostic indices (PIs) were created adding in Ki67, grade and ER to RCB. Leave-one-out cross-validation was used to reduce bias. The overall change in χ(2) of the best model for each index was used to compare the prognostic ability of the different indices. RESULTS: All PIs provided significant prognostic information for patients with residual disease following neoadjuvant chemotherapy. RPCB (χ(2) = 61.4) was significantly more prognostic than either RCB (χ(2) = 38.1) or Ki67 (χ(2) = 53.8) alone P < 0.001. A PI incorporating RCB, Ki67 grade and ER provided the most prognostic information overall and gave χ(2) = 73.8. CONCLUSIONS: This study provides proof of principle that the addition of post-treatment Ki67 to RCB improves the prediction of long-term outcome. Prediction may be further improved by addition of post-treatment grade and ER and warrants further investigation for estimating post-neoadjuvant risk of recurrence. These indices may have utility in stratifying patients for novel therapeutic interventions after neoadjuvant chemotherapy.

The radiological excision of high risk and malignant lesions using the INTACT breast lesion excision system. A case series with an imaging follow up of at least 5 years.

PURPOSE: To evaluate the efficacy of a BLES procedure as a primary excisional biopsy rather than a surgical wide local excision for treatment of a high risk or a malignant lesion. METHODS: 41 patients underwent a BLES procedure in order to attempt to remove a small breast lesion using a 15 mm or 20 mm wand from August 2007 to January 2009. The lesions were either proven on prior core biopsy to show high risk or malignant pathology or were considered to be indeterminate or suspicious on ultrasound or mammography. The pathology was reviewed to include the final status of lesion excision. If margin involvement was demonstrated then a formal surgical excision was subsequently recommended. Follow up mammography or ultrasound was performed annually in patients following the final pathological diagnosis. RESULTS: 9 patients had a primary diagnosis of atypia (columnar cell change with atypia or atypical ductal hyperplasia (ADH)), 23 patients had ductal carcinoma in situ (DCIS) and 9 had an invasive carcinoma (IC) at the original BLES pathology. Clear BLES margins of >1 mm were obtained in 3/9 atypia lesions, 15/23 DCIS and 0/9 IC. 12/13 low grade DCIS were completely excised. Subsequent surgical margin excisions were undertaken in 20 patients. After at least 5 years of follow up (mean 66 months), 1 lesion had recurred on imaging. CONCLUSION: A BLES excision has potential as an alternative technique to traditional surgical wide local excision in the management of certain small breast lesions with high risk and low grade malignant potential.

Myoepithelial expression of Fas and strong nuclear expression of FasL in epithelial cells: a marker for risk stratification of breast cancer.

AIM: The clinical significance of Fas and FasL in hormone-sensitive carcinomas has been reported. Our objective was to evaluate the expression of apoptosis-regulating genes Fas and FasL in Indian breast cancer and fibroadenoma patients in relation to hormone receptor status. STUDY DESIGN: Retrospective. MATERIALS AND METHODS: Paraffin-embedded tissue samples from 63 untreated female patients with invasive ductal carcinoma (IDC) and 32 female patients with fibroadenoma were studied. Expression of Fas and FasL was evaluated using immunohistochemical staining method. STATISTICAL ANALYSIS: Fisher's exact test and nonparametric correlation test (Spearman rank correlation test) were performed. RESULT: Fas was detected in 97% of the fibroadenomas and there was a slight decrease in levels of expression with histological grades of IDC. The expression of FasL was detected in 75% fibroadenomas and its expression increased in IDC. There was no correlation between Fas, FasL expression and hormone receptor status. Strong expression of Fas in myoepithelial cells was noted in 12 out of 32 fibroadenoma cases. CONCLUSION: Expression of Fas and FasL alone is unlikely to be important as a predictive factor as they express in both normal and malignant breast epithelium. But strong expression of Fas in myoepithelial cells along with strong nuclear expression of FasL in epithelial cells of fibroadenoma could be useful as an early predictive factor for onset of malignancy.

Nutrients determine the spatial architecture of Paracoccus sp. biofilm.

Bacterial biofilms adapt and shape their structure in response to varied environmental conditions. A statistical methodology was adopted in this study to empirically investigate the influence of nutrients on biofilm structural parameters deduced from confocal scanning laser microscope images of Paracoccus sp.W1b, a denitrifying bacterium. High concentrations of succinate, Mg(++), Ca(++), and Mn(++) were shown to enhance biofilm formation whereas higher concentration of iron decreased biofilm formation. Biofilm formed at high succinate was uneven with high surface to biovolume ratio. Higher Mg(++) or Ca(++) concentrations induced cohesion of biofilm cells, but contrasting biofilm architectures were detected. Biofilm with subpopulation of pillar-like protruding cells was distributed on a mosaic form of monolayer cells in medium with 10 mM Mg(++). 10 mM Ca(++) induced a dense confluent biofilm. Denitrification activity was significantly increased in the Mg(++)- and Ca(++)-induced biofilms. Chelator treatment of various biofilm ages indicated that divalent cations are important in the initial stages of biofilm formation.

Discordance between core needle biopsy (CNB) and excisional biopsy (EB) for estrogen receptor (ER), progesterone receptor (PgR) and HER2 status in early breast cancer (EBC).

BACKGROUND: Analysis of estrogen receptor (ER), progesterone receptor (PgR) and HER2 status in early breast cancer (EBC) is increasingly being conducted in core needle biopsies (CNBs) taken at diagnosis but the concordance with the excisional biopsy (EB) is poorly documented. PATIENTS AND METHODS: Patients with EBC presenting to The Royal Marsden Hospital from June 2005 to September 2007 who had CNB and subsequent EB were included. ER and PgR were determined by immunohistochemistry (IHC) and graded from 0 to 8 (Allred score). HER2 was determined by IHC and scored from 0 to 3+. FISH analysis was carried out in HER2 2+ cases and in discordant cases. RESULTS: In all, 336 pairs of samples were compared. ER was positive in 253 CNBs (75%) for 255 EBs (76%) and was discordant in six patients (1.8%). PgR was positive in 221 CNBs (66%) and 227 (67.6%) EBs being discordant in 52 cases (15%). HER2 was positive in 41 (12.4%) of the 331 CNBs in which it was determined compared with 44 (13.3%) EBs and discordant in four cases (1.2%). CONCLUSIONS: CNB can be used with confidence for ER and HER2 determination. For PgR, due to a substantial discordance between CNB and EB, results from CNB should be used with caution.

Malignant myoepithelioma arising in adenomyoepithelioma of the breast and coincident multiple gastrointestinal stromal tumours in a patient with neurofibromatosis type 1.

A 41-year-old female patient with neurofibromatosis type 1 (NF-1) presented with a breast lump and anaemia related to gastrointestinal bleeding. She was found to have malignant myoepithelioma of the breast and simultaneously multiple gastrointestinal stromal tumours (GISTs) of the small bowel. Molecular studies showed a silent germline mutation in exon 9 of the KIT gene of both tumours. The common gene mutations characteristic of sporadic GISTs were not identified in these tumours, consistent with the literature, suggesting that gene mutations in GISTs are either absent or late events in patients with NF-1.

Expression of survivin and p53 proteins and their correlation with hormone receptor status in Indian breast cancer patients.

BACKGROUND: In invasive ductal carcinoma (IDC), many antiapoptotic and proapoptotic genes regulate disease outcome. Hormone receptor-mediated mechanisms have also been shown to prevent apoptosis. Therefore, relations between hormone receptor status and other molecular markers need further examination. AIMS: In the present study, we analyzed the expression of apoptosis-regulating genes, viz., Survivin and mutant p53, in benign breast disease (fibroadenoma) and IDC patients. Results were then correlated with hormone receptor status of the patients. MATERIAL AND METHODS: Paraffin-embedded tissue samples from 63 untreated female patients with IDC and 32 female patients with fibroadenoma were used. Expression of Survivin and mutant p53 was evaluated using immunohistochemical staining method. STATISTICAL ANALYSIS: Fisher exact test and nonparametric correlation test (Spearman rank correlation test) were performed. Results : In fibroadenoma, 53% of patients expressed Survivin and 13% of patients expressed p53 protein. Statistically significant increase in Survivin and p53 protein expression was observed in carcinoma cases. Survivin expression correlated negatively with progesterone receptor (PR) status, but its expression was independent of estrogen receptor (ER) status. p53 expression showed negative correlation with both ER and PR status. CONCLUSIONS: Increased expression of Survivin and p53 in IDC patients and correlation with hormone receptors suggest that Survivin and p53 along with hormone receptors status are likely to contribute significantly to apoptosis resistance and may serve as therapeutic target that could increase the effectiveness of conventional breast cancer therapy.

Platinum-based chemotherapy in triple-negative breast cancer.

BACKGROUND: Experimental data suggest that triple-negative (TN) breast cancer may have increased sensitivity to platinum-based chemotherapy but clinical data are limited. We present our long-term results with platinum-based chemotherapy for TN breast cancer. PATIENTS AND METHODS: In all, 94 (17 TN), 79 (11 TN) and 155 (34 TN) patients receiving platinum-based chemotherapy in neo-adjuvant/adjuvant and advanced setting were included. Response rates and outcome were compared for TN tumours versus others. RESULTS: Neo-adjuvant complete response rates were significantly higher for TN tumours (88%) than others (51%; P = 0.005). The 5-year overall survival (OS) for TN tumours following adjuvant/neo-adjuvant chemotherapy was 64% [95% confidence interval (CI) 44% to 79%] compared with 85% (95% CI 79% to 90%) for others. Five-year disease-free survival for TN tumours was 57% (95% CI 37% to 73%) compared with 72% (95% CI 64% to 78%) for others. For patients with advanced breast cancer, overall response rates were 41% for TN tumours and 31% for others (P = 0.3). Patients with TN tumours had a significantly prolonged progression-free survival of 6 months compared with 4 months for others (P = 0.05), though the OS was not significantly different between the two groups (11 versus 7 months). CONCLUSION: Platinum-based chemotherapy achieves increased response rates for TN tumours, with a trend towards worse survival in early breast cancer through an improved survival in advanced disease. Prospective randomised trials are warranted.

Hypoxia can be detected in irradiated normal human tissue: a study using the hypoxic marker pimonidazole hydrochloride.

Chronic tissue hypoxia may play a role in the pathogenesis of late radiation fibrosis. In order to investigate this hypothesis, the immunohistochemical distribution of pimonidazole hydrochloride (n = 14 patients) and carbonic anhydrase IX (CAIX) (n = 38 patients) was studied in samples of previously irradiated normal human tissue. One sample of irradiated breast tissue, which also showed marked histological features of radiation injury, stained positive for pimonidazole hydrochloride. No CAIX staining was seen in irradiated tissue other than some evidence of physiological hypoxia in the epidermis of two samples of irradiated skin; both were positive for pimonidazole and one was focally positive for CAIX. Pimonidazole hydrochloride staining of tissue with morphological changes of radiation injury could support a role for hypoxia in the pathogenesis of late normal tissue fibrosis in humans.

Circulating Immune complexes (CIC) as marker for disease progress in oral cancer.

Oral Cancer is one of the five leading sites of cancer in Indian population. The circulating immune complexes were investigated in 100 serum samples of 60 oral cancer patients having different grades of the disease and 40 patients with precancerous lesions obtained from Nair Hospital Dental collage, Mumbai. The results obtained were compared with those of group of 40 healthy blood donors. Elevated levels of Circulating Immune Complexes were observed in oral cancer patients and patients with oral precancerous lesions. 92% positive samples were observed in well differentiated squamous cell carcinoma whereas 100% positive samples were observed in both moderately and poorly differentiated squamous cell carcinoma. Oral leukoplakia and oral submucous fibrosis showed 15% and 90% positivity respectively. Increased level of Circulating Immune complexes in high grade tumor suggest that Circulating Immune complexes is likely to contribute in evaluating the degree of malignancy, but follow up study is needed to draw any conclusion regarding it's prognostic role.

Breast carcinoma and malignant melanoma metastasis within a single axillary lymph node.

A 58 year old lady presented with a right breast cancer and a prior history of malignant melanoma excised from the right chest wall eight years previously. An abnormal axillary lymph node resected contained features of both metastatic breast carcinoma and malignant melanoma. Following oncologic breast cancer management, the patient is well with no evidence of recurrence at three years.

Cost-effectiveness of screening with contrast enhanced magnetic resonance imaging vs X-ray mammography of women at a high familial risk of breast cancer.

Contrast enhanced magnetic resonance imaging (CE MRI) is the most sensitive tool for screening women who are at high familial risk of breast cancer. Our aim in this study was to assess the cost-effectiveness of X-ray mammography (XRM), CE MRI or both strategies combined. In total, 649 women were enrolled in the MARIBS study and screened with both CE MRI and mammography resulting in 1881 screens and 1-7 individual annual screening events. Women aged 35-49 years at high risk of breast cancer, either because they have a strong family history of breast cancer or are tested carriers of a BRCA1, BRCA2 or TP53 mutation or are at a 50% risk of having inherited such a mutation, were recruited from 22 centres and offered annual MRI and XRM for between 2 and 7 years. Information on the number and type of further investigations was collected and specifically calculated unit costs were used to calculate the incremental cost per cancer detected. The numbers of cancer detected was 13 for mammography, 27 for CE MRI and 33 for mammography and CE MRI combined. In the subgroup of BRCA1 (BRCA2) mutation carriers or of women having a first degree relative with a mutation in BRCA1 (BRCA2) corresponding numbers were 3 (6), 12 (7) and 12 (11), respectively. For all women, the incremental cost per cancer detected with CE MRI and mammography combined was pound28 284 compared to mammography. When only BRCA1 or the BRCA2 groups were considered, this cost would be reduced to pound11 731 (CE MRI vs mammography) and pound15 302 (CE MRI and mammography vs mammography). Results were most sensitive to the unit cost estimate for a CE MRI screening test. Contrast-enhanced MRI might be a cost-effective screening modality for women at high risk, particularly for the BRCA1 and BRCA2 subgroups. Further work is needed to assess the impact of screening on mortality and health-related quality of life.

Increased survivin expression in high-grade oral squamous cell carcinoma: a study in Indian tobacco chewers.

BACKGROUND: Oral cancer is one of the five leading sites of cancer in the Indian population. In the present study we analyzed the expression of apoptosis regulating genes, viz. survivin, Bcl-2, Bax and p53 in precancerous and cancerous lesions of the buccal mucosa of Indian tobacco chewers. METHOD: Paraffin-embedded tissue samples from 38 patients with primary oral squamous cell carcinoma (OSCC) and 17 patients with leukoplakia were used. The expression of survivin, Bcl-2, Bax, and p53 was evaluated using immunohistochemical staining method. RESULTS: Thirty-six percent OSCC were found to be positive for nuclear p53 staining while none of the precancerous lesions showed p53 positivity. Survivin, Bcl-2 and Bax expression was found to increase with increased grade of malignancy. Increase in survivin expression was statistically most significant (P < 0.001). CONCLUSION: Increased expression of anti-apoptotic survivin in high-grade tumors suggests that survivin is likely to contribute significantly to apoptosis resistance in response to therapy.