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Biomedical subjects

M Michael

Publications and source records attributed to M Michael.

At least 19 recordsLinked to original sources
PubMed2006

A phase I/II trial of celecoxib with chemotherapy and radiotherapy in the treatment of patients with locally advanced oesophageal cancer.

BACKGROUND: The study's aim was to determine the maximum tolerated dose (MTD) of celecoxib combined with chemoradiotherapy (CRT) for locally advanced oesophageal cancer (OC). METHODS: CRT comprised of 5FU (1000 mg/m(2)/day, days 1-4, weeks 1 & 5), cisplatin (75 mg/m(2), days 1 & 29) and radiotherapy (50 Gy in 25 fractions or 50.4 Gy in 28 fractions). Celecoxib was given daily during CRT at one of five doses (200 mg bd to 600 mg bd). Three to six patients were assigned per dose. RESULTS: Thirteen patients were recruited before trial closure due to external safety concerns regarding celecoxib. Median follow up was 17 months (95% CI 9 - >39). The highest administered dose was 400 mg bd (n=4) with one dose-limiting toxicity at this level: grade 3 rash. Five (38%) and 8(62%) patients had grade 3 non-haematological and haematological toxicities respectively. No grade 4 toxicities occurred. Radiological response rate was 54% (n=7: all CR). Six patients had resection with one pathological CR. Median progression-free and overall survival were 8.8 (95% CI 5.1 - >24.8) and 19.6 months (95% CI 7.3 - >39) respectively. CONCLUSIONS: A MTD was not reached. The regimen was tolerable, indicating that celecoxib can be safely administered with CRT for locally advanced OC.

Adenocarcinoma↗
PubMed2006

Molecular characterization of the bacteria adherent to human colorectal mucosa.

AIMS: To study large intestinal mucosal bacterial communities by Denaturing Gradient Gel Electrophoresis (DGGE) profiling and sequencing of 16S rRNA gene polymerase chain reaction (PCR) products amplified from DNA extracted from colorectal biopsies taken from healthy individuals. The specific aims were to determine how similar the mucosa-associated bacterial communities are within and between individuals and also to characterize the phylogenetic origin of isolated DGGE bands. METHODS AND RESULTS: Human colorectal biopsies were taken at routine colonoscopy from 33 patients with normal looking mucosa. The DNA was extracted directly from single biopsies and the bacterial 16S rDNA PCR amplified. The PCR products were profiled using DGGE to generate a fingerprint of the dominant members of the bacterial community associated with the biopsy. The reproducibility of this method was high (>98%). Washed and unwashed biopsies gave similar DGGE banding patterns (Median Similarity Coefficient - MSC 96%, InterQuartile Range - IQR 3.0%, n = 5). Adjacent biopsies sampled from the same patient using different forceps gave similar DGGE profiles (MSC 94%, n = 2). Two colorectal biopsies sampled at locations 2-5 cm apart, from each of 18 patients, resulted in very similar profiles (MSC 100%, IQR 2.8%). Biopsies sampled from different locations within the large intestine of the same patient also gave similar DGGE profiles (MSC 98% IQR 3.3%n = 6). Although all patients (n = 33) gave different DGGE profiles, some similarity (c. 34%) was observed between profiles obtained from 15 patients arbitrarily selected. 35 DGGE bands were excised and sequenced. Many were found to be most closely related to uncultured bacterial sequence entries in the Genbank database. Others belonged to typical gut bacterial genera including Bacteroides, Ruminococcus, Faecalibacterium and Clostridium. CONCLUSIONS: Bacterial communities adherent to colorectal mucosa within a normal patient show little variation; in contrast, mucosal bacterial communities sampled from different patients with normal colorectal mucosa show a high degree of variation. SIGNIFICANCE AND IMPACT OF THE STUDY: This research demonstrates that DGGE profiling of 16S rRNA gene PCR products amplified from DNA extracted directly from mucosal samples offers fresh insight into the bacterial communities that are adherent to colorectal mucosa. These findings are important with respect to further studies on the gastrointestinal tract in health and disease.

Adenomatous Polyposis Coli↗
PubMed2006

Hypoxia-inducible factors HIF-1alpha and HIF-2alpha expression in bladder cancer and their associations with other angiogenesis-related proteins.

Hypoxia-inducible factors (HIF-1alpha and HIF-2alpha) are closely related protein complexes that activate transcription of target genes in response to hypoxia. The immunohistochemical expression of these two proteins was investigated in 144 bladder cancer tissue samples and correlated with standard clinicopathological features, in order to elucidate their prognostic significance. We also evaluated their possible associations with other angiogenesis related markers such as microvessel density (MVD), vascular endothelial growth factor, thymidine phosphorylase, tenascin, fibronectin, p53 and bcl-2 to further clarify their implication in tumor stroma vascularization. Nuclear HIF-1alpha expression in tumor cells was detected in 57.1% of the cases. A trend of correlation of this expression with poorly differentiated tumors was observed. In addition, HIF-1alpha expression was positively correlated with stromal cells thymidine phosphorylase expression. Tumors that were progressed in muscle-infiltrating disease showed a higher HIF-1alpha expression. A higher HIF-1alpha expression was also observed in tumors with an in situ component. In tumor cells, low HIF-2alpha expression was observed in 6.3%, moderate in 31.9% and high in 61.8% of the cases. A trend of correlation of this expression with MVD was observed. In addition, HIF-2alpha expression was positively correlated with thymidine phosphorylase and fibronectin expression. A lower HIF-2alpha expression was detected in tumors that recurred earlier in univariate methods of analysis. HIF-2alpha was expressed in tumor stroma associated cells in 53.5% of specimens and was correlated with advance tumor stage, thymidine phosphorylase and tenascin expression. There was no statistically significant difference in the expression of both HIF-1alpha and HIF-2alpha between primary and recurrent tumors. In multivariate analysis including T stage, T grade, multifocality and T size, both HIF-1alpha and HIF-2alpha expression were not considered dependent in the prediction of recurrence or progression. In conclusion, the results of the present study indicate that HIF-1alpha and HIF-2alpha expression may help to predict recurrence or progression to muscle invasive disease but not as independent prognostic factors. In addition, the expression of HIF-1alpha and HIF-2alpha, appear to play a role in bladder cancer, vascularization possibly and in cooperation with other angiogenic factors.

Adult↗
PubMed2005

A phase I trial of high-dose palliative radiotherapy plus concurrent weekly Vinorelbine and Cisplatin in patients with locally advanced and metastatic NSCLC.

The role of concurrent chemoradiotherapy (CRT) in patients with non-small-cell lung cancer (NSCLC) unsuitable for radical therapy but who require locoregional treatment has not been defined. The aims of this phase I trial were thus to develop a novel regimen of weekly chemotherapy concurrent with high-dose palliative RT (40 Gy/20 fractions) and assess its tolerability, objective and symptomatic response rates. Eligible patients had stage I-IIIB NSCLC unsuitable for radical RT or limited stage IV disease, ECOG PS<or=1 and required locoregional therapy. Treatment was RT (40 Gy/20 fractions/5 per week) and weekly Vinorelbine plus Cisplatin escalated in six planned dose levels (DLs). At 4 weeks post-RT, patients received two cycles of Cisplatin 80 mg m-2 day 1+Vinorelbine 25 mg m-2 days 1, 8, 15. Dose-limiting toxicities (DLTs) were defined in the CRT phase. Disease-related symptoms were assessed by the Lung Cancer Symptom Scale. In all, 24 patients accrued, stage IIIB (n=12) and IV disease (n=10). The highest administered dose was at DL 4, Vinorelbine 30 mg m-2+Cisplatin 20 mg m-2 with DLTs of grade 4 neutropenia in two of three patients. No grade 3 or 4 nonhaematological toxicities were observed. The overall radiological response rate was 65% (n=23: complete response 4% and partial response 61%) and infield FDG-PET responses were seen in 89% (n=18). There was an improvement or stabilisation of symptoms and quality of life. Dose level 3, Vinorelbine 25 mg m-2+Cisplatin 20 mg m-2, is recommended for further assessment. This regimen was tolerable and produced meaningful responses for patients for whom locoregional control is required, but who are unsuitable for radical CRT.

Adult↗
PubMed2005

Australian experience of a modified schedule of FOLFOX with high activity and tolerability and improved convenience in untreated metastatic colorectal cancer patients.

This study determined the efficacy and safety of a modified FOLFOX regimen that improved patient convenience without compromising oxaliplatin dose intensity. A total of 62 patients with previously untreated metastatic colorectal cancer were enrolled to receive, entirely as outpatients, 2-weekly cycles of oxaliplatin 100 mg m(-2) i.v. over 2 h, together with leucovorin 400 mg m(-2) over 2 h, 5-fluorouracil (5-FU) 400 mg m(-2), bolus, followed by a 46-h infusion of 5-FU at 2.4 g m(-2). Treatment was given until progression or unmanageable toxicity. In all, 61 patients received > or =one oxaliplatin dose and a median of 11 treatment cycles (range 1-20 cycles); 22 (36%) reported grade 3/4 neutropenia and 13 patients (21%) experienced grade 3 neurotoxicity; 16 patients (26%) discontinued treatment due to disease progression or death, 15 (25%) due to neurotoxicity and six (10%) due to haematological toxicity. Of the 56 eligible patients, complete or partial responses were observed in 29 or 52% (95% confidence interval 38-65%). Median progression-free survival was 8.2 months (7.1-9.9) and median overall survival was 18.7 months (14.0-23.4). In our experience, a modified schedule of FOLFOX improves convenience without compromising efficacy or toxicity.

Adult↗
PubMed2005

Oxaliplatin combined with infusional 5-fluorouracil and concomitant radiotherapy in inoperable and metastatic rectal cancer: a phase I trial.

The aim of this study was to define the recommended dose of oxaliplatin when combined with infusional 5-fluorouracil (5-FU) and concurrent pelvic radiotherapy. Eligible patients had inoperable rectal cancer, or symptomatic primary rectal cancer with metastasis. Oxaliplatin was given on day 1 of weeks 1, 3 and 5 of radiotherapy. Dose level 1 was oxaliplatin 70 mg m(-2) with 5-FU 200 mg m(-2) day(-1) continuous infusion 96 h week(-1). On dose level 2, the oxaliplatin dose was increased to 85 mg m(-2). On dose level 3, the duration of the 5-FU was increased to 168 h per week. Pelvic radiotherapy was 45 Gray (Gy) in 25 fractions over 5 weeks with a boost of 5.4 Gy. Fluorine-18 fluoro deoxyglucose and Fluorine-18 fluoro misonidazole positron emission tomography (FDG-PET and FMISO-PET) were used to assess metabolic tumour response and hypoxia. In all, 16 patients were accrued. Dose-limiting toxicities occurred in one patient at level 2 (grade 3 chest infection), and two patients at level 3 (grade 3 diarrhoea). Dose level 2 was declared the recommended dose level. FDG-PET imaging showed metabolic responses in 11 of the 12 primary tumours assessed. Four of six tumours had detectable hypoxia on FMISO-PET scans. The addition of oxaliplatin to infusional 5-FU chemoradiotherapy was feasible and generally well tolerated. For future trials, oxaliplatin 85 mg m(-2) and 5-FU 200 mg m(-2) day(-1) continuous infusion 96 h week(-1) is the recommended dose when combined with 50.4 Gy of pelvic radiotherapy.

Adult↗
PubMed2005

Tumoral drug metabolism: overview and its implications for cancer therapy.

Drug-metabolizing enzymes (DME) in tumors are capable of biotransforming a variety of xenobiotics, including antineoplastics, resulting in either their activation or detoxification. Many studies have reported the presence of DME in tumors; however, heterogeneous detection methodology and patient cohorts have not generated consistent, firm data. Nevertheless, various gene therapy approaches and oral prodrugs have been devised, taking advantage of tumoral DME. With the need to target and individualize anticancer therapies, tumoral processes such as drug metabolism must be considered as both a potential mechanism of resistance to therapy and a potential means of achieving optimal therapy. This review discusses cytotoxic drug metabolism by tumors, through addressing the classes of the individual DME, their relevant substrates, and their distribution in specific malignancies. The limitations of preclinical models relative to the clinical setting and lack of data on the changes of DME with disease progression and host response will be discussed. The therapeutic implications of tumoral drug metabolism will be addressed-in particular, the role of DME in predicting therapeutic response, the activation of prodrugs, and the potential for modulation of their activity for gain are considered, with relevant clinical examples. The contribution of tumoral drug metabolism to cancer therapy can only be truly ascertained through large-scale prospective studies and supported by new technologies for tumor sampling and genetic analysis such as microarrays. Only then can efforts be concentrated in the design of better prodrugs or combination therapy to improve drug efficacy and individualize therapy.

Animals↗
PubMed2005

Prognostic significance of thymidine phosphorylase in superficial bladder carcinoma.

OBJECTIVE: We investigated the expression of thymidine phosphorylase (TP) in bladder carcinomas and assessed its prognostic significance in superficial bladder cancer samples. PATIENTS AND METHODS: We studied 142 primary bladder cancer samples immunohistochemically for nuclear thymidine phosphorylase (TPN), cytoplasmic (TPC) and stromal (TPSTR) expression. We correlated them with standard clinicopathological features (grade, stage, concurrent in situ, multiplicity, primary or recurrent status), as well with recurrence and progression. We examined also the relationship between TP and tumor microvessel density. RESULTS: The level of all types of TP correlated well with stage, while grade correlated well only with TPSTR and the presence of carcinoma in situ only with TPN. Patients with low levels of TPN had a longer tumor free interval, during a 38.6 months mean follow up time. Regarding the association between TP count and microvessel density we found the strongest association with TPSTR (p=0.003), a borderline statistical significance with TPC (p=0.049) and no relationship with TPN (p=0.072). CONCLUSIONS: We suggest that the assessment of TPN might be useful for predicting recurrence in superficial bladder cancer. We propose also that TP may stimulate angiogenesis.

Aged↗
PubMed2005

Inflammatory bowel disease-related dysplasia and cancer: A referral center study in northwestern Greece.

BACKGROUND: An increased risk of colorectal cancer in ulcerative colitis (UC) and Crohn's disease (CD) has been reported. No data on inflammatory bowel disease (IBD)-related dysplasia and cancer is available in Greece, where the disease profile seems to be milder than that of northern Europe. METHODS: A study was conducted of 215 IBD patients (182 with UC, 33 with CD) from a referral center. Patients were followed up for 3-18 years. The prevalence of cancer and dysplasia among the IBD patients who were diagnosed in northwestern Greece was analyzed and registered. Statistical analysis was performed assuming that this IBD cohort had the same risk of developing malignancies as the general population in Greece. RESULTS: Six of the 215 patients in this IBD cohort had cancer, and 20 of 126 patients for whom bowel biopsies were available had dysplasia. Three of these cases were high-grade dysplasia. There was no significant difference in the numbers of calculated and expected cases of IBD-related cancer at any sites except for the skin [2.7 vs. 2.0]. CONCLUSIONS: This IBD cohort did not appear to have an increased risk of cancer during the time period studied. It would be interesting to re-assess the risk after the second and third decades of follow-up.

Journal Article↗
PubMed2005

[Diagnostic assessment of painless microhematuria: prospective study comparing image quality, assessibility and diagnostic certainty of multidetector-row CT and intravenous pyelography within a single examination].

PURPOSE: The purpose of this study is to prospectively compare intravenous pyelography (IVP) and combined unenhanced and excretory phase multidetector-row CT (MDCT) with respect to image quality, diagnostic certainty and diagnostic concordance with the final clinical diagnosis in patients with painless microhematuria. MATERIALS AND METHODS: Unenhanced MDCT, IVP and excretory phase MDCT were performed in 59 consecutive patients (21 women, 38 men, mean age 56 +/- 19 years, range 23 - 83 years) with painless microhematuria of unknown origin during a single examination with a single contrast media application (100 ml, non-ionic iodinated contrast media). Images were assessed by two experienced urogenital radiologists in consensus for image quality, diagnostic certainty of stone detection, obstruction, parenchymal lesions and morphological distinctive features. Imaging diagnoses of MDCT and IVP were compared with the final clinical diagnoses. In case of failure to detect an relevant pathology, the final clinical diagnosis was established after a mean follow-up period of 18 +/- 6 months (10 months to 2 years). Costs and radiation exposure of IVP and MDCT were compared. RESULTS: MDCT scan performed better than IVP in terms of image quality for all regarded variables. Image quality of MDCT was rated in all parameters as very good or good; the image quality of IVP differed in a wide range. MDCT and IVP reached a sensitivity of 100 % and 50 % for stone detection (n = 14, p = 0.008), respectively. Two bladder stones were not detected by IVU but correctly seen with MDCT. MDCT and IVP were unsatisfactory for detecting transitional cell carcinomas (n = 4, 2 of 4 detected with MDCT, 0 of 4 detected with IVU). One false positive transitional cell carcinoma was detected with IVP, none with MDCT. Additional relevant pathological changes (one teratoma, one abdominal aortic aneurysma and one abscess) were detected using MDCT but missed with IVP. In 38 of 59 patients (64 %) imaging and clinical follow-up over up to 24 months did not reveal any pathology to explain the microhematuria. The costs of the IVP (283 Euro) were lower compared with non-enhanced MDCT (380 Euro) or combined non-enhanced and contrast-enhanced MDCT (560 Euro). The radiation exposure was 23 - 27 mSv for MDCT and 2.3 mSv for IVP. CONCLUSION: MDCT performed better regarding image quality, subjective diagnostic certainty and diagnostic results with respect to stone detection. Since urolithiasis is a frequent cause of painless microhematuria MDCT is recommended as the initial imaging modality rather than IVU.

Adult↗
PubMed2005

Gastrointestinal stromal tumour treated with neoadjuvant imatinib.

This report describes a case of unresectable primary gastrointestinal stromal tumour (GIST) treated with imatinib on a neoadjuvant basis, before subsequent successful surgical resection. After six months of imatinib, computed tomography and positron emission tomography imaging demonstrated a significant size reduction and complete metabolic response to treatment, rendering the tumour resectable. Mutational analysis showed an activating KIT mutation in exon 11. The pathological appearance of the resected tumour was heterogeneous with extensive necrosis, cystic and myxoid change, extensive hypocellularity, and patchy foci of residual viable tumour. The implications for this management option of radiological, pathological, and molecular assessment are discussed.

Aged↗
PubMed2004

A phase I trial of preoperative radiotherapy and capecitabine for locally advanced, potentially resectable rectal cancer.

The purpose of the study was to determine the maximum-tolerated dose (MTD) of oral capecitabine, combined with concurrent, standard preoperative pelvic radiotherapy, when given twice daily, from Monday to Friday throughout the course of radiotherapy, for locally advanced potentially resectable rectal cancer. Maximum-tolerated dose was defined as the total (given in two equally divided doses) oral dose of capecitabine that caused treatment-related grade 3 or 4 toxicity in one-third or more of the patients treated. Radiotherapy involved 50.4 Gy given in 28 fractions in 5 weeks and 3 days. Eligible patients had a newly diagnosed clinical stage T3-4 N0-2 M0 rectal adenocarcinoma located within 12 cm of the anal verge suitable for curative resection. Surgery was performed 4-6 weeks from completion of preoperative chemoradiotherapy. In all, 28 patients were enrolled in the study at predefined dose levels: 850 mg m(-2) day(-1) (n=3), 1000 mg m(-2) day(-1) (n=6), 1250 mg m(-2) day(-1) (n=3), 1650 mg m(-2) day(-1) (n=3), 1800 mg m(-2) day(-1) (n=8) and 2000 mg m(-2) day(-1) (n=5). The mean age was 62.3 years (range: 33-80 years). Five patients were female and 23 male. The median distance of tumour from the anal verge was 6 cm (range: 1-11 cm). Endorectal ultrasound was performed in 93% of patients. A total of 26 patients (93%) had T3 disease and two patients had resectable T4 disease. Dose-limiting toxicity (DLT) developed in one patient at dose level 1000 mg m(-2) day(-1) (RTOG grade 3 cystitis). Two of the five patients at dose level 2000 mg m(-2) day(-1) had a total of three DLT (grade 3 perineal skin reaction, grade 3 diarrhoea and grade 3 dehydration). Dose escalation of capecitabine was ceased at 2000 mg m(-2) day(-1) after reaching MTD. None of the eight patients at dose level 1800 mg m(-2) day(-1) developed DLT. All except one patient underwent surgery. A total of 15 patients had the clinical T stage reduced by at least one stage in pathologic specimens. Five patients (19%) achieved a pathologic complete response. We conclude that the MTD of capecitabine was reached at a dose level of 2000 mg m(-2) day(-1), given as 1000 mg m(-2) twice daily, from Monday to Friday throughout the course of preoperative pelvic irradiation of 50.4 Gy. For patients with resectable rectal cancer receiving concurrent, full dose radiotherapy, the recommended dose of capecitabine for further study is 1800 mg m(-2) day(-1) when given in this schedule.

Adenocarcinoma↗
PubMed2004

Prognostic significance of angiogenesis in superficial bladder cancer.

OBJECTIVE: To assess the prognostic significance of angiogenesis parameters such as microvessel density (MVD) and vascular endothelial growth factor (VEGF) in superficial bladder cancer. PATIENTS AND METHODS: We studied 127 superficial bladder cancer samples immunohistochemically for the above factors. We compared them with standard clinicopathological features (grade, stage, concurrent in situ, multifocality, primary or recurrent status) as well as with p53 expression, recurrence and progression to muscle infiltrating disease. RESULTS: During a 36 months median follow up of 109 patients with superficial primary tumors (min. 3, max. 69 months), 80 of them recurred (73.4%), while 8 patients (7.3%) progressed to muscle invading disease. A significant correlation was noted between MVD and VEGF in all 127 samples (p = 0.019). No association was noted between MVD or VEGF with the other clinicopathological features, recurrence or progression. Although progression free survival rates of categorized microvessel density (up to and higher than median value) differed significantly only in grade 3 patients, no independent prognostic significance could be attributed to MVD. No correlation was observed between MVD or VEGF with p53 protein. CONCLUSIONS: Based on our data we suggest that VEGF is not useful for predicting recurrence or progression in superficial bladder cancer. Microvessel density determination may help to predict progression of grade 3 patients to muscle invasive disease but not as an independent prognostic factor.

Adult↗
PubMed2004

Expression patterns of cyclins D1, E and cyclin-dependent kinase inhibitors p21(Waf1/Cip1) and p27(Kip1) in urothelial carcinoma: correlation with other cell-cycle-related proteins (Rb, p53, Ki-67 and PCNA) and clinicopathological features.

INTRODUCTION: The expression pattern of cyclins D1 and E, as well as cyclin-dependent kinase inhibitors p21(Wa1/Cip1) and p27(Kip1) and their relationship to tumour behaviour and patients' prognosis was examined in 142 urothelial cell carcinomas. The expression of these proteins was also analyzed along with other cell-cycle-related proteins such as: p53, pRb and the proliferation-associated indices Ki-67 and proliferating cell nuclear antigen (PCNA). PATIENTS AND METHODS: These molecule markers were localized immunochemically using the monoclonal antibodies anti-cyclin D1 (DCS-6), anti-cyclin E (13A3), anti-p21 (4D10), and anti-p27 (1B4) in 142 patients with urothelial cell carcinoma. RESULTS: Focal positivity (<10% of tumour cells) or the absence of cyclin D1 immunostaining was observed in 105/142 (73.9%) of the tumours. Cyclin D1 expression was correlated with tumour grade and stage as well as with the existence of in situ component. In addition, cyclin D1 expression was positively correlated with p21(Waf1/Cip1) and p27(Kip1) and inversely with the Ki-67 score. Focal positivity (<20% of tumour cells) or the absence of cyclin E immunoreactivity was observed in 105/142 (73.9%) in all cases. Cyclin E expression was correlated with tumour stage. A positive relationship between cyclin E expression and the two associated proliferating indices Ki-67 and PCNA, as well as with p53 and p27(Kip1) proteins expression was noted. Absence or focal positivity (<5% of tumour cells) of p21(Waf1/Cip1) was detected in 88/142 (62%) of the carcinomas. p21(Waf1/Cip1) expression was correlated with tumour grade and stage. A positive relationship of its expression cyclin D1, cyclin E, p27 and pRb expression was observed. Absence or focal immunostaining (<20% of tumour cells) of p27 protein was detected in 55/141 (39%) in all cases. p27(Kip1) expression was correlated with tumour grade as well as with cyclins D1 and E. The prognostic significance of cyclins D1, E and cyclin-dependent kinase inhibitors p21(Waf1/Cip1), p27(Kip1) in determining the risk of recurrence and progression with both univariate (log rank test) and multivariate (Cox regression) methods of analysis showed no statistically significance differences. CONCLUSION: These findings suggest that the level of the cell cycle regulators studied does not seem to have a clinical value in terms of predicting the risk of early recurrence and progression. In addition the interrelationship probably means their contribution to the regulation of cell growth through different pathways in bladder carcinogenesis.

Adult↗
PubMed2004

Expression patterns of cyclins D1, E in laryngeal epithelial lesions: correlation with other cell cycle regulators (p53, pRb, Ki-67 and PCNA) and clinicopathological features.

The expression of cell-cycle progression molecules cyclin D1 and cyclin E were immunohistochemically examined in a series of 64 squamous cell invasive carcinomas of the larynx, 10 in situ carcinomas, 34 cases of dysplasia, 11 papillomas and 23 cases of keratosis. The results of their expression were compared with two cell-cycle implicated tumor suppressor proteins p53 and pRb as well as with two proliferation associated indices PCNA and Ki-67 in an attempt to elucidate their potential role in the pathogenesis and progression of these lesions. Nuclear staining for cyclin D1 and E (>5% positive cells) was observed in 19% and 39.7% of the laryngeal carcinomas, respectively. Significantly elevated levels of cyclin D1 and E in invasive laryngeal carcinomas compared with in situ carcinomas were revealed (p=0.045 and p=0.0003, respectively). High levels of cyclin D1 and E expression were correlated with increased Ki-67 score (p=0.037 and 0.017 respectively). A significant positive correlation between cyclin D1 and E was also detected in carcinomas (p=0.018). Decreased levels of cyclins D1 and E in the group of in situ carcinomas compared with those of dysplastic cases and papillomas were also observed. In the dysplastic lesions cyclin D1 expression was correlated with pRb expression (p=0.02). In the cases of keratosis cyclins D1 and E expression were correlated with pRb (p=0.002 and p=0.036, respectively), while cyclin D1 was associated with PCNA (p=0.008) and Ki-67 score (p=0.009). The prognostic significance of cyclins D1, E in determining the risk of recurrence and overall survival with both univariate (long-rang test) and multivariate (Cox regression) methods of analysis showed no statistically significant differences. We conclude that the expression of cyclins D1 and E in squamous cell carcinomas of the larynx does not seem to have a prognostic significance. In addition, their expression may be involved in the development of laryngeal lesions, implicated in cell proliferation, with other cell cycle related proteins, probably by different molecular pathways.

Adult↗
PubMed2003

Adjuvant and neoadjuvant therapy for gastric cancer using epirubicin/cisplatin/5-fluorouracil (ECF) and alternative regimens before and after chemoradiation.

Chemoradiation is now used more commonly for gastric cancer following publication of the US Intergroup trial results that demonstrate an advantage to adjuvant postoperative chemoradiotherapy. However, there remain concerns regarding the toxicity of this treatment, the optimal chemotherapy regimen and the optimal method of radiotherapy delivery. In this prospective study, we evaluated the toxicity and feasibility of an alternative chemoradiation regimen to that used in the Intergroup trial. A total of 26 patients with adenocarcinoma of the stomach were treated with 3D-conformal radiation therapy to a dose of 45 Gy in 25 fractions with concurrent continuous infusional 5-fluorouracil (5-FU). The majority of patients received epirubicin, cisplatin and 5-FU (ECF) as the systemic component given before and after concurrent chemoradiation. The overall rates of observed grade 3 and 4 toxicities were 38 and 15%, respectively. GIT grade 3 toxicity was observed in 19% of patients, while haematologic grade 3 and 4 toxicities were observed in 23%. Our results suggest that this adjuvant regimen can be delivered safely and with acceptable toxicity. This regimen forms the basis of several new studies being developed for postoperative adjuvant therapy of gastric cancer.

Adenocarcinoma↗
PubMed2003

Identification of the minor component of a mixed stain by using mismatch primer-induced restriction sites in amplified mtDNA.

We report a case in which STR typing failed to identify the minor component of a mixed saliva stain, but a mitochondrial restriction analysis succeeded in discriminating between the two components. To identify the nt16093 and nt16265 transitions, the template was amplified with the mismatch primers L16092-mm16085 and H16266-mm16269. In the presence of the transitions the mismatch primers created a BsaB I and a Cac8 I restriction site, respectively. Subsequently, aliquots were restricted separately using the enzymes Cac8 I and BsaB I which clearly identified the minor stain component.

Beverages↗
PubMed2003

Short versus standard duration oral antibiotic therapy for acute urinary tract infection in children.

BACKGROUND: The optimal duration of oral antibiotic therapy for urinary tract infection (UTI) in children has not been determined. A number of studies have compared single dose therapy to standard therapy for UTI, with mixed results. A course of antibiotics longer than a single dose but shorter than the usual 7-10 days might decrease the relapse rate and still provide some of the benefits of a shortened course of antibiotics. OBJECTIVES: The objective of this review was to assess the benefits and harms of short-course (2-4 days) compared to standard duration (7-14 days) oral antibiotic treatment for acute UTI in children. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Cochrane Library Issue 3, 2002) MEDLINE (1966 - September 2002) and EMBASE (1988 -September 2002) without language restriction. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing short-term (2-4 days) with standard (7-14 days) oral antibiotic therapy were selected if they studied children aged three months to 18 years with culture proven UTI. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) with 95% confidence intervals (95% CI). MAIN RESULTS: Ten trials were identified in which 652 children with lower tract UTI were evaluated. There was no significant difference in the frequency of positive urine cultures between the short (2-4 days) and standard duration oral antibiotic therapy (7-14 days) for UTI in children at 0-10 days after treatment (eight studies: RR 1.06; 95% CI 0.64 to 1.76) and at one to 15 months after treatment (10 studies: RR 0.95; 95% CI 0.70 to 1.29). There was no significant difference between short and standard duration therapy in the development of resistant organisms in UTI at the end of treatment (one study: RR 0.57, 95% CI 0.32 to 1.01) or in recurrent UTI (three studies: RR 0.39, 95% CI 0.12 to 1.29). REVIEWER'S CONCLUSIONS: A 2-4 day course of oral antibiotics appears to be as effective as 7-14 days in eradicating lower tract UTI in children.

Acute Disease↗