Mycosis fungoides (MF) is the most common type of primary cutaneous T-cell lymphoma (CTCL). To identify a molecular signature characteristic of MF tumor stage, we used a bioinformatic approach ...involving meta-analysis of publicly available gene expression data sets combined with previously generated gene expression data. Results for a selection of genes were further refined and validated by quantitative PCR and inclusion of additional controls. With this approach, we identified a profile specific for MF tumor stage, consisting of 989 aberrantly expressed genes, the majority of which (718 genes) are statistically significantly more expressed in MF compared with normal skin, inflamed skin, and normal T cells. As expected, the signature contains genes reflecting the highly proliferative characteristic of this T-cell malignancy, including altered expression of cell cycle and kinetochore regulators. We uncovered details of the immunophenotype, suggesting that MF originates from IL-32-producing cells and identified previously unreported therapeutic targets and/or diagnostic markers, for example, GTSF1 and TRIP13. Loss of expression of the NF-κB inhibitor, NFKBIZ, may partly explain the enhanced activity of NF-κB, which is a hallmark of MF and other CTCLs.
To investigate the correlation between family history of prostate cancer (PCa) and survival (overall and cancer specific) in patients undergoing treatment for PCa.
ine thousand four hundred ...fifty-nine patients with PCa were extracted from the South Australian Prostate Cancer Clinical Outcomes Collaborative (SA-PCCOC) database. Diagnosis occurred after 1998 and treatment before 2014. Cox proportional-hazards modeling was used to assess the effect of family history on overall survival after adjustment for confounders (age at diagnosis, NCCN risk category and year of treatment), and with stratification by primary treatment group. Competing risks regression modelling was used to assess PCa specific mortality.
Men with a positive family history of PCa appear to have a lower Gleason score at the time of diagnosis (50% with Gleason < 7, compared to 39% in those without family history) and be diagnosed at a lower age (64 vs 69). Men with a positive family history of PCa appear to have better overall survival outcomes (p < 0.001, log rank test). In analysis adjusting for age at diagnosis, NCCN risk category and year of treatment, family history remained a significant factor when modelling overall survival (HR 0.72 95% CI 0.55-0.95, p = 0.021). There were no significant differences in treatment subgroups of radical prostatectomy (p = 0.7) and radiotherapy (0.054).
Men with a positive family history of PCa appear to have better overall survival outcomes. This better survival may represent lead time bias and early initiation of PSA screening. Family history of PCa was not associated with different survival outcomes in men who were treated with either radical prostatectomy or radiotherapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Several studies have investigated cardiac dose reduction when utilizing the deep inspiration breath hold (DIBH) technique in patients undergoing radiotherapy for left-sided breast cancer. This paper ...aims to recommend potential selection criteria based on a retrospective single institute study of free breathing (FB) and DIBH computed tomography (CT) simulation planning scans.
Dosimetric comparisons were performed retrospectively for 20 patients correlating the dose reduction and patient anatomical factors (anatomical variation of chest shape, chest wall separation, total lung volume (TLV) and others).
Paired t-tests demonstrated significant cardiac dose reduction for most patients but not all. Minimal cardiac dose reduction was observed for three patients using their DIBH plan, with one patient receiving a higher dose. Linear regression analysis identified a positive correlation between the patient's TLV (on the FB CT simulation scan) and the magnitude of dosimetric benefit received (0.4045 R²).
The TLV measured on a FB plan could potentially be utilised to predict cardiac exposure and assist with patient selection for DIBH. This is important in resource allocation, as DIBH may be unnecessarily recommended for some patients with little dosimetric benefit.
The human cytomegalovirus (HCMV), potentially associated with the development of malignancies, encodes the constitutively active chemokine receptor US28. Previously, we have shown that US28 ...expression induces an oncogenic phenotype both in vitro and in vivo. Microarray analysis revealed differential expression of genes involved in oncogenic signaling in US28-expressing NIH-3T3 cells. In particular, the expression of cyclooxygenase-2 (COX-2), a key mediator of inflammatory diseases and major determinant in several forms of cancer, was highly up-regulated. US28 induced increases in COX-2 expression via activation of nuclear factor-kappaB, driving the production of vascular endothelial growth factor. Also, in HCMV-infected cells, US28 contributed to the viral induction of COX-2. Finally, the involvement of COX-2 in US28-mediated tumor formation was evaluated using the COX-2 selective inhibitor Celecoxib. Targeting COX-2 in vivo with Celecoxib led to a marked delay in the onset of tumor formation in nude mice injected with US28-transfected NIH-3T3 cells and a reduction of subsequent growth by repressing the US28-induced angiogenic activity. Hence, the development of HCMV-related proliferative diseases may partially be ascribed to the ability of US28 to activate COX-2.
Introduction
The role of the radioprotector amifostine in ameliorating radiotherapy side effects in head and neck squamous cell carcinoma (HNSCC) is controversial. This trial aimed to determine ...whether pretreatment with amifostine reduced the incidence of Radiation Therapy Oncology Group grade ≥2 acute and late xerostomia in patients receiving definitive or adjuvant radiotherapy for HNSCC, without reducing tumour control or survival.
Methods
Between 14 September 2001 and 8 November 2004, 44 Royal Adelaide Hospital patients were randomized double‐blind to receive amifostine (200 mg/m2 IV) or placebo (normal saline IV) 5 days/week, prior to standard radiotherapy (60–70 Gy), each having ≥75% of the parotids treated to ≥40 Gy. Side effects were assessed weekly during treatment, at 3 and 5 months after radiotherapy, then every 6 months until disease progression or death.
Results
The accrual target was 200 patients over 4–5 years, but the trial closed prematurely when only 44 patients had been randomized after 3 years. Of 41 evaluable patients, 80% (16/20) in the amifostine arm had grade ≥2 acute radiation salivary toxicity versus 76% (16/21) in the placebo arm (P = 1.00). The rate of grade ≥2 late radiation salivary toxicity at 12 months was 66% in the amifostine arm and 82% in the placebo arm (estimated hazard ratio 1.61, 95% confidence interval 0.74–3.49, P = 0.22). Other toxicities tended to be worse in the amifostine arm: acute grade 3–4 skin 35% vs 5% and mucous membrane 40% vs 5%; grade ≥2 vomiting 35% vs 5%, hypocalcaemia 25% vs 5% and fatigue 85% vs 33%, with only the latter retaining statistical significance after adjusting for multiple comparisons. There were no significant differences in failure‐free (P = 0.70) or overall survival (P = 0.86), with estimated 4‐year rates of 48% vs 54% and 49% vs 59% for the amifostine vs placebo arms respectively.
Conclusion
There was no clear evidence that pretreatment with amifostine made any difference to the incidence of grade ≥2 acute or late xerostomia. Other toxicity tended to be more severe with amifostine. There was no effect on failure‐free or overall survival. Acknowledging the low statistical power, these results do not support the use of IV amifostine pre‐radiotherapy in HNSCC.
Bank transactions are highly confidential. As a result, there are no real public data sets that can be used to investigate and compare anti-money laundering (AML) methods in banks. This severely ...limits research on important AML problems such as efficiency, effectiveness, class imbalance, concept drift, and interpretability. To address the issue, we present SynthAML: a synthetic data set to benchmark statistical and machine learning methods for AML. The data set builds on real data from Spar Nord, a systemically important Danish bank, and contains 20,000 AML alerts and over 16 million transactions. Experimental results indicate that performance on SynthAML can be transferred to the real world. As use cases, we present and discuss open problems in the AML literature.
A previous, unblinded study demonstrated that an alcohol-free barrier film containing an acrylate terpolymer (ATP) was effective in reducing skin reactions compared with a 10% glycerine cream ...(sorbolene). The different appearances of these products precluded a blinded comparison. To test the acrylate terpolymer principle in a double-blinded manner required the use of an alternative cream formulation, a moisturizing durable barrier cream (MDBC); the study was conducted by the Trans Tasman Radiation Oncology Group (TROG) as protocol 04.01.
A total of 333 patients were randomized; 1 patient was ineligible and 14 patients withdrew or had less than 7 weeks' observations, leaving 318 for analysis. The chest wall was divided into medial and lateral compartments, and patients were randomized to have MDBC applied daily to the medial or lateral compartment and sorbolene to the other compartment. Weekly observations, photographs, and symptom scores (pain and pruritus) were collected to week 12 or resolution of skin reactions if earlier. Skin dose was confirmed by centrally calibrated thermoluminescent dosimeters.
Rates of medial and lateral compartment Common Toxicity Criteria (CTC), version 3, greater than or equal to grade 3 skin reactions were 23% and 41%, but rates by skin care product were identical at 32%. There was no significant difference between MDBC and sorbolene in the primary endpoint of peak skin reactions or secondary endpoints of area-under-the-curve skin reaction scores.
The MDBC did not reduce the peak skin reaction compared to sorbolene. It is possible that this is related to the difference in the formulation of the cream compared with the film formulation. Skin dosimetry verification and double blinding are essential for radiation skin care comparative studies.
To determine the extent and impact of upgrading and downgrading among men who underwent radical prostatectomy (RP) according to new grade groupings and to identify predictors of upgrading from biopsy ...grade Group I and II, and downgrading to grade Group I, in a community setting.
Study participants included 2279 men with non-metastatic prostate cancer diagnosed 2006–2015 who underwent prostatectomy, from the multi-institutional South Australia Prostate Cancer Clinical Outcomes Collaborative registry. Extent of up- or down-grading was assessed by comparing biopsy and prostatectomy grade groupings. Risk of biochemical recurrence (BCR) with upgrading was assessed using multivariable competing risk regression. Binomial logistic regression was used to identify pre-treatment predictors of upgrading from grade Groups I and II, and risk group reclassification among men with low risk disease.
Upgrading occurred in 35% of cases, while downgrading occurred in 13% of cases. Sixty percent with grade Group I disease were upgraded following prostatectomy. Upgrading from grade Group I was associated with greater risk of BCR compared with concordant grading (Hazard ratio: 3.1, 95% confidence interval: 1.7–6.0). Older age, higher prostate-specific antigen levels (PSA), fewer biopsy cores, higher number of positive cores and more recent diagnosis predicted upgrading from grade Group I, while higher PSA and clinical stage predicted upgrading from grade Group II. No clinical risk factors for reclassification were identified.
Biopsy sampling errors may play an important role in upgrading from grade Group I. Improved clinical assessment of grade is needed to encourage greater uptake of active surveillance.
To report quality of life (QOL) results for patients receiving chemoradiation therapy for pancreatic cancer.
Eligible patients (n=41 locally advanced, n=22 postsurgery) entered the B9E-AY-S168 study ...and received 1 cycle of induction gemcitabine (1000 mg/m2 weekly ×3 with 1-week break) followed by 3-dimensional conformal radiation therapy (RT) (54 Gy locally advanced and 45 Gy postsurgery) and concomitant continuous-infusion 5-fluorouracil (5FU) (200 mg/m2/d throughout RT). After 4 weeks, patients received an additional 3 cycles of consolidation gemcitabine chemotherapy. Patients completed the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-PAN26 questionnaires at baseline, before RT/5FU, at end of RT/5FU, before consolidation gemcitabine, and at treatment completion.
The patterns of change in global QOL scores differed between groups. In the locally advanced group global QOL scores were +13, +8, +3, and +1 compared with baseline before RT/5FU (P=.008), at end of RT/5FU, before consolidation gemcitabine, and at treatment completion, respectively. In the postsurgery group, global QOL scores were -3, +4, +15, and +17 compared with baseline at the same time points, with a significant improvement in global QOL before consolidation gemcitabine (P=.03). No significant declines in global QOL were reported by either cohort.
This study demonstrates that global QOL and associated function and symptom profiles for pancreatic chemoradiation therapy differ between locally advanced and postsurgery patients, likely owing to differences in underlying disease status. For both groups, the treatment protocol was well tolerated and did not have a negative impact on patients' global QOL.
Introducing e-books into Swedish libraries has been influenced by the idea of equal access to all media for all Swedish citizens as well as by librarians’ wish to provide the best possible service to ...their users. Libraries perceived this new resource and service as a way of fulfilling their specific function in a democratic society, which is usually described as mediation (or transfer) of knowledge and culture to all. This is a common basis for the incorporation of new media and information resources (including e-books) into Swedish academic and public libraries. Apart from this common platform, we see other similarities in working with e-books in both types of libraries, but also a number of differences. Most of them relate to the position of libraries within their respective context and in relation to their specific role. Academic libraries are quite influential players in the global scholarly communication and supporters of both research and study processes. As such they are embedded in a mainly international market of scientific information and scholarly materials. They have significant resources provided by their parent universities for the acquisition of scholarly material and a wide choice of commercially available material from different providers. They are also incorporated into a national library consortium with great negotiation power. Thus, they have more freedom to experiment with a variety of business and pricing models offered on the international market. They also have a high competence in publishing and are often publishers themselves. Their involvement in research processes and in open access initiatives puts them in a position to provide expertise to researchers in the areas of publishing and intellectual property protection. Public libraries are part of the local cultural and educational landscape. As such, they depend on the production of media and content in national languages which helps cater to the needs and demands of the local population. They are also customers on the limited market of publishing, entertainment and education-related materials which help fulfil their function as educators. As public libraries offer open and free access to their resources to the entire population of a certain area, eventually covering the whole country, they are regarded as a disruptive element in the market economy. This perceived threat from public libraries was reborn with the emergence of e-books. Despite their differences, both academic and public libraries face similar challenges and problems relating to the management of their collections, creating metadata, and providing access to their content. So far, there haven’t been any mutually satisfactory solutions.
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