The Role of Chemotherapy in Upper Tract Urothelial Carcinoma

Locally advanced upper tract urothelial carcinoma has a poor prognosis. While surgery represents the only potentially curable therapeutic intervention, recurrences are common and typically systemic in nature. It is thus reasonable to consider perioperative chemotherapy in an effort to decrease the risk of recurrence. There are very little direct data providing clinical guidance in this scenario. For urothelial cancer of the bladder, there are randomized phase III data demonstrating a survival advantage with neoadjuvant cisplatin-based combination chemotherapy. Although arguments favoring adjuvant chemotherapy could be made for upper tract urothelial cancer, the loss of renal function that occurs with nephrectomy can complicate administration of appropriate perioperative treatment. Therefore, by analogy to urothelial carcinoma of the lower tract, it is argued that cisplatin-based neoadjuvant chemotherapy should be the standard of care for patients with locally advanced upper tract urothelial cancer

Brain choline concentrations may not be altered in euthymic bipolar disorder patients chronically treated with either lithium or sodium valproate

BACKGROUND: It has been suggested that lithium increases choline concentrations, although previous human studies examining this possibility using (1)H magnetic resonance spectroscopy ((1)H MRS) have had mixed results: some found increases while most found no differences. METHODS: The present study utilized (1)H MRS, in a 3 T scanner to examine the effects of both lithium and sodium valproate upon choline concentrations in treated euthymic bipolar patients utilizing two different methodologies. In the first part of the study healthy controls (n = 18) were compared with euthymic Bipolar Disorder patients (Type I and Type II) who were taking either lithium (n = 14) or sodium valproate (n = 11), and temporal lobe choline/creatine (Cho/Cr) ratios were determined. In the second part we examined a separate group of euthymic Bipolar Disorder Type I patients taking sodium valproate (n = 9) and compared these to controls (n = 11). Here we measured the absolute concentrations of choline in both temporal and frontal lobes. RESULTS: The results from the first part of the study showed that bipolar patients chronically treated with both lithium and sodium valproate had significantly reduced temporal lobe Cho/Cr ratios. In contrast, in the second part of the study, there were no effects of sodium valproate on either absolute choline concentrations or on Cho/Cr ratios in either temporal or frontal lobes. CONCLUSIONS: These findings suggest that measuring Cho/Cr ratios may not accurately reflect brain choline concentrations. In addition, the results do not support previous suggestions that either lithium or valproate increases choline concentrations in bipolar patients

The Massive and Distant Clusters of WISE Survey V: Extended Radio Sources in Massive Galaxy Clusters at z~1

We present the results from a pilot study with the Karl G. Jansky Very Large Array (JVLA) to determine the radio morphologies of extended radio sources and the properties of their host-galaxies in 10 massive galaxy clusters at z~1, an epoch in which clusters are assembling rapidly. These clusters are drawn from a parent sample of WISE-selected galaxy clusters that were cross-correlated with the VLA Faint Images of the Radio Sky at Twenty-Centimeters survey (FIRST) to identify extended radio sources within 1$^{\prime}$ of the cluster centers. Out of the ten targeted sources, six are FR II sources, one is an FR I source, and three sources have undetermined morphologies. Eight radio sources have associated Spitzer data, 75% presenting infrared counterparts. A majority of these counterparts are consistent with being massive galaxies. The angular extent of the FR sources exhibits a strong correlation with the cluster-centric radius, which warrants further investigation with a larger sample.Comment: accepted to Ap

Utility of patient-derived lymphoblastoid cell lines as an ex vivo capecitabine sensitivity prediction model for breast cancer patients.

Capecitabine is commonly used in treating breast cancer; however, therapeutic response varies among patients and there is no clinically validated model to predict individual outcomes. Here, we investigated whether drug sensitivity quantified in ex vivo patients' blood-derived cell lines can predict response to capecitabine in vivo. Lymphoblastoid cell lines (LCLs) were established from a cohort of metastatic breast cancer patients (n = 53) who were prospectively monitored during treatment with single agent capecitabine at 2000 mg/m2/day. LCLs were treated with increasing concentrations of 5'-DFUR, a major capecitabine metabolite, to assess patients' ex vivo sensitivity to this drug. Subsequently, ex vivo phenotype was compared to observed patient disease response and drug induced-toxicities. We acquired an independent cohort of breast cancer cell lines and LCLs derived from the same donors from ATCC, compared their sensitivity to 5'-DFUR. As seen in the patient population, we observed large inter-individual variability in response to 5'-DFUR treatment in patient-derived LCLs. Patients whose LCLs were more sensitive to 5'-DFUR had a significantly longer median progression free survival (9-month vs 6-month, log rank p-value = 0.017). In addition, this significant positive correlation for 5'-DFUR sensitivity was replicated in an independent cohort of 8 breast cancer cell lines and LCLs derived from the same donor. Our data suggests that at least a portion of the individual sensitivity to capecitabine is shared between germline tissue and tumor tissue. It also supports the utility of patient-derived LCLs as a predictive model for capecitabine treatment efficacy in breast cancer patients

Comprehensive Immune Monitoring of Clinical Trials to Advance Human Immunotherapy.

The success of immunotherapy has led to a myriad of clinical trials accompanied by efforts to gain mechanistic insight and identify predictive signatures for personalization. However, many immune monitoring technologies face investigator bias, missing unanticipated cellular responses in limited clinical material. We present here a mass cytometry (CyTOF) workflow for standardized, systems-level biomarker discovery in immunotherapy trials. To broadly enumerate immune cell identity and activity, we established and extensively assessed a reference panel of 33 antibodies to cover major cell subsets, simultaneously quantifying activation and immune checkpoint molecules in a single assay. This assay enumerates ≥98% of peripheral immune cells with ≥4 positively identifying antigens. Robustness and reproducibility are demonstrated on multiple samples types, across two research centers and by orthogonal measurements. Using automated analysis, we identify stratifying immune signatures in bone marrow transplantation-associated graft-versus-host disease. Together, this validated workflow ensures comprehensive immunophenotypic analysis and data comparability and will accelerate biomarker discovery

The Scottish economy [February 1986]

With the inauguration of the quarterly Scottish Business Survey (SBS) in September 1984 there are now two regular up-to-date indicators of trends in the Scottish industrial sector. The combination of the new survey and the long-standing CBI Industrial Trends Survey provides a comprehensive assessment of trends in Scottish industry. The two data sources are essentially complementary, but there are important differences between them

The British economy [February 1986]

Growth in the UK economy looks set to continue in 1986 although at a lower rate than in preceding years. Consumer expenditure will play a dominant role in determining growth while exports and investment will expand less rapidly than in 1985. In the November Statement the Chancellor forecast further reductions in the inflation rate and reductions in income tax in the Spring Budget. Unlike previous years, however, the Chancellor provided no clear indication of the likely scale of tax cuts. Avoidance of any specific commitment has now been proven wise as the Exchequer's revenues have been reduced by falling oil prices

Outlook and appraisal [February 1986]

During the course of 1986 economic growth in Scotland and in the rest of the UK is likely to proceed less rapidly than in 1985. Moreover, changes in the Scottish pattern of growth will reflect those taking place in the UK generally and in other European economies

The world economy [February 1986]

The present recovery in the world economy has now proceeded for almost twice as long as the typical cyclical phase of expansion during the past four decades. Growth in 1985 and prospective growth for 1986 is, however, modest in comparison to both the rates achieved in earlier upswings and that of 1983-4 when world expansion was driven by the strong growth of the US economy. With the deceleration of the US economy from its phase of rapid expansion and the continuing policy caution in the countries of Western Europe and Japan, growth in the major industrialised economies is likely to be of the order of 2.5% in 1986