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

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

Analysis of clinical characteristics, management and survival of patients with Ta T1 bladder tumours in Sweden between 1997 and 2001

Objective. To analyse the management and outcome of patients with Ta T1 urinary bladder cancer in a population-based national database. Material and methods. Between 1997 and 2001, 94% of all newly diagnosed cases of urinary bladder cancer were registered in the Swedish National Bladder Cancer Register. Data were analysed regarding gender, healthcare region, stage and grade for patients with Ta T1 tumours. The choice of initial treatment in different regions was reviewed. Survival was analysed by calculating relative survival. Results. Out of 9859 registered patients, there were 4442 Ta tumours and 2139 T1 tumours. The median age at diagnosis was 72 and 73 years for patients with Ta and T1 tumours, respectively. Seventy-six percent of the patients were men. The choice of treatment varied between different healthcare regions. A significant trend towards an increased use of intravesical therapy was seen over time. Significantly fewer older than younger patients received such therapy. There was also a tendency towards more intensive therapy in men. The bladder cancer relative 5-year survival rate was 93% for Ta and 75% for T1 tumours. Survival was similar for men and women. Conclusions. Our analysis revealed a regional variation in the treatment of bladder cancer. A large group of patients, even those at high risk, were still undertreated. However, the recent publication of guidelines may have contributed to an increased use of intravesical treatment. Urologists tended to treat TaG3 and T1G3 tumours more aggressively than T1G2 tumours. Therapeutic aggressiveness decreased as the age of the patients increased. The survival rate of patients with bladder cancer in Sweden seems to remain at the levels previously reported for the 1980s

Change of Body Movement Coordination during Cervical Proprioceptive Disturbances with Increased Age.

Background: To date, there are very few studies on postural stability in older adults using body movement recordings to capture the postural movement pattern. Moreover, the importance of proprioception at key areas such as the calf or neck on the postural movement pattern in older adults has rarely been investigated. Objective: To investigate whether the body movement coordination strategy to calf or neck vibration was affected by aging. Methods: Body movement measurements were taken at five locations (ankle, knee, hip, shoulder and head) from 18 younger (mean age 29.1 years) and 16 older (mean age 71.5 years) adult subjects using a 3D movement measuring system while subjected to 50 s of pseudo-random calf or neck vibratory stimulation pulses with eyes open or closed. The positions from the knee, hip, shoulder and head markers were correlated against one another to give an indication of the body coordination. Results: During quiet standing, older adults had greater correlation between the head and trunk than the young. There was an age effect in the body movement coordination strategy. Older adults had a different movement pattern with neck vibration involving mainly more independent knee movements, indicating balance difficulty. Conclusions: Neck vibration affects the movement pattern in older adults more compared with younger adults and calf vibration, suggesting that, the regulation of body orientation in older adults is more difficult, especially during cervical proprioceptive disturbances

Association between insulin-like growth factor-1 receptor (IGF1R) negativity and poor prognosis in a cohort of women with primary breast cancer

Background: Resistance towards endocrine therapy is a great concern in breast cancer treatment and may partly be explained by the activation of compensatory signaling pathways. The aim of the present study was to investigate if the insulin-like growth factor-1 receptor (IGF1R) signaling pathway was activated or deregulated in breast cancer patients and to explore if any of the markers were prognostic, with or without adjuvant tamoxifen. This signaling pathway has been suggested to cause estrogen independent cell growth and thus contribute to resistance to endocrine treatment in estrogen receptor (ER) positive breast cancer. Methods: The protein expression of IGF1R, phosphorylated Mammalian Target of Rapamycin (p-mTOR) and phosphorylated S6 ribosomal protein (p-S6rp) were investigated by immunohistochemistry using tissue microarrays in two patient cohorts. Cohort I (N = 264) consisted of mainly postmenopausal women with stage II breast cancer treated with tamoxifen for 2 years irrespective of ER status. Cohort II (N = 206) consisted of mainly medically untreated, premenopausal patients with node-negative breast cancer. Distant disease-free survival (DDFS) at 5 years was used as end-point for survival analyses. Results: We found that lower IGF1R expression was associated with worse prognosis for tamoxifen treated, postmenopausal women (HR = 0.70, 95% CI = 0.52 - 0.94, p = 0.016). The effect was seen mainly in ER-negative patients where the prognostic effect was retained after adjustment for other prognostic markers (adjusted HR = 0.49, 95% CI = 0.29 - 0.82, p = 0.007). Expression of IGF1R was associated with ER positivity (p less than 0.001) in the same patient cohort. Conclusions: Our results support previous studies indicating that IGF1R positivity reflects a well differentiated tumor with low metastatic capacity. An association between lack of IGF1R expression and worse prognosis was mainly seen in the ER-negative part of Cohort I. The lack of co-activation of downstream markers (p-mTOR and p-S6rp) in the IGF1R pathway suggested that the prognostic effect was not due to complete activation of this pathway. Thus, no evidence could be found for a compensatory function of IGF1R signaling in the investigated cohorts.Funding Agencies|Swedish Cancer Society; Swedish Research Council; Gunnar Nilsson Cancer Foundation; Mrs. Berta Kamprad Foundation; Anna and Edwin Bergers foundation; Skane University Hospital Research Foundation; Skane County Councils Research and Development Foundation; Governmental Funding of Clinical Research within the National Health Service</p