An overview on preclinical and clinical experiences with photodynamic therapy for bladder cancer

Photodynamic therapy (PDT) is one of the most interesting methods of photo treatment. In general, PDT is a modality for the treatment of non-muscle invasive tumors. PDT is very well suited in managing bladder cancer, as the bladder is accessible by endoscopy and the tumors are most often limited to the mucosa or sub-mucosa. PDT is likely more useful for patients with recurrent tumors after conventional therapies, as well as for patients with diffuse non-muscle invasive bladder carcinomas that are refractory to standard treatments before the commitment to radical extirpative surgery, particularly in patients at surgical high risk. The treatment of tumors with PDT includes three major parameters: presence of oxygen in tumor tissue, administration of a photosensitizer, and subsequent exposure to light. The PDT mechanism relies on the in situ generation of cytotoxic agents by the activation of a light-sensitive drug, resulting in cell death. In this review, we present past and current advances in the use of PDT with urinary bladder cancer and discuss the future roles for this type of therapy in the treatment of bladder cancer

Validation of a breast cancer assay for radiotherapy omission: an individual participant data meta-analysis

Background: There are currently no molecular tests to identify individual breast cancers where radiotherapy (RT) offers no benefit. Profile for the Omission of Local Adjuvant Radiotherapy (POLAR) is a 16-gene molecular signature developed to identify low risk cancers where RT will not further reduce recurrence rates. Methods: An individual participant data meta-analysis was performed in 623 cases of node-negative ER+/HER2-negative early breast cancer enrolled in three RT randomized trials for whom primary tumor material was available for analysis. A Cox proportional hazards model on time to locoregional recurrence (LRR) was used to test the interaction between POLAR score and RT.Results: 429 (69%) patients’ tumors had a high POLAR score and 194 (31%) had a low score. Patients with high POLAR score had, in the absence of RT, a 10-year cumulative incidence of LRR: 20% (15%-26%) vs 5% (2%-11%) for those with a low score. Patients with a high POLAR score had a large benefit from RT (hazard ratio [HR] for RT vs no RT: 0.37 [0.23-0.60], p&lt;0.001). In contrast, there was no evidence of benefit from RT for patients with a low POLAR score (HR: 0.92 [0.42-2.02], p = 0.832). The test for interaction between RT and POLAR was statistically significant (p = 0.022).Conclusions: POLAR is not only prognostic for locoregional recurrence but also predictive of benefit from radiotherapy in selected patients. Patients ≥ 50 years with ER+/HER2-negative disease and a low POLAR score could consider omitting adjuvant RT. Further validation in contemporary clinical cohorts is required.<br/

Are there differences in all-cause and coronary heart disease mortality between immigrants in Sweden and in their country of birth? A follow-up study of total populations

BACKGROUND: Mortality from cardiovascular diseases is higher among immigrants than native Swedes. It is not clear whether the high mortality persists from the country of birth or is a result of migration. The purpose of the present study was to analyse whether all-cause and coronary heart disease mortality differ between immigrants in Sweden and in the country of birth. METHODS: Two cohorts including the total population from Swedish national registers and WHO were defined. All-cause and CHD mortality are presented as age-adjusted incidence rates and incidence density ratios (IDR) in eight immigrant groups in Sweden and in their country of birth. The data were analysed using Poisson regression. RESULTS: The all-cause mortality risk was lower among seven of eight male immigrant groups (IDR 0.39–0.97) and among six of eight female immigrant groups (IDR 0.42–0.81) than in their country of birth. The CHD mortality risk was significantly lower in male immigrants from Norway (IDR = 0.84), Finland (IDR = 0.91), Germany (IDR = 0.84) and Hungary (IDR = 0.59) and among female immigrants from Germany (IDR = 0.66) and Hungary (IDR = 0.54) than in their country of birth. In contrast, there was a significantly higher CHD mortality risk in male immigrants from Southern Europe (IDR = 1.23) than in their country of birth. CONCLUSION: The all-cause mortality risk was lower in the majority of immigrant groups in Sweden than in their country of birth. The differences in CHD mortality risks were more complex. For countries with high CHD mortality, such as Finland and Hungary, the risk was lower among immigrants in Sweden than in their country of birth. For low-risk countries in South Europe, the risk was higher in immigrants in Sweden than in South Europe

Khoe-San genomes reveal unique variation and confirm the deepest population divergence in Homo sapiens

Abstract: The southern African indigenous Khoe-San populations harbor the most divergent lineages of all living peoples. Exploring their genomes is key to understanding deep human history. We sequenced 25 full genomes from five Khoe-San populations, revealing many novel variants, that 25% of variants are unique to the Khoe-San, and that the Khoe-San group harbors the greatest level of diversity across the globe. In line with previous studies, we found several gene regions with extreme values in genome-wide scans for selection, potentially caused by natural selection in the lineage leading to Homo sapiens and more recent in time. These gene regions included immunity-, sperm-, brain-, diet-, and muscle-related genes. When accounting for recent admixture, all Khoe-San groups display genetic diversity approaching the levels in other African groups and a reduction in effective population size starting around 100,000 years ago. Hence, all human groups show a reduction in effective population size commencing around the time of the Out-of- Africa migrations, which coincides with changes in the paleoclimate records, changes that potentially impacted all humans at the time

Contribution of Chondroitin Sulfate A to the Binding of Complement Proteins to Activated Platelets

Exposure of chondroitin sulfate A (CS-A) on the surface of activated platelets is well established. The aim of the present study was to investigate to what extent CS-A contributes to the binding of the complement recognition molecule C1q and the complement regulators C1 inhibitor (C1INH), C4b-binding protein (C4BP), and factor H to platelets.Human blood serum was passed over Sepharose conjugated with CS-A, and CS-A-specific binding proteins were identified by Western blotting and mass spectrometric analysis. C1q was shown to be the main protein that specifically bound to CS-A, but C4BP and factor H were also shown to interact. Binding of C1INH was dependent of the presence of C1q and then not bound to CS-A from C1q-depleted serum. The specific interactions observed of these proteins with CS-A were subsequently confirmed by surface plasmon resonance analysis using purified proteins. Importantly, C1q, C4BP, and factor H were also shown to bind to activated platelets and this interaction was inhibited by a CS-A-specific monoclonal antibody, thereby linking the binding of C1q, C4BP, and factor H to exposure of CS-A on activated platelets. CS-A-bound C1q was also shown to amplify the binding of model immune complexes to both microtiter plate-bound CS-A and to activated platelets.This study supports the concept that CS-A contributes to the binding of C1q, C4BP, and factor H to platelets, thereby adding CS-A to the previously reported binding sites for these proteins on the platelet surface. CS-A-bound C1q also seems to amplify the binding of immune complexes to activated platelets, suggesting a role for this molecule in immune complex diseases