tbuckley/cabot-search huggingface dataset:
LBH589, a novel histone deacetylase inhibitor (HDACi), treatment of patients with cutaneous T-cell lymphoma (CTCL). Changes in skin gene expression profiles related to clinical response following therapy
Authors: H. M. Prince, D. J. George, R. Johnstone, R. Williams-Truax, P. Atadja, C. Zhao, M. Dugan, K. Culver
Journal: Journal of Clinical Oncology (2006)

7501 Background: LBH589 is a novel histone deacetylase inhibitor in Phase I trials. Since other HDACi have induced disease regression in CTCL, we evaluated the activity of LBH589 and resulting changes in gene expression of LBH589 in CTCL patients (pts). Methods: Pts with advanced-stage CTCL, who had progressed following prior systemic therapy were entered into the DLT dose level 30mg M,W,F cohort (n = 1) or the subsequent MTD dose level 20mg M,W, F weekly (n = 10). LBH589 was continued until disease progression or unacceptable toxicity. The first three pts had 3mm punch biopsies from CTCL-involved skin lesions at 0, 4, 8 and 24h after administration, which were subjected to gene expression profiling using Affymetrix U133 plus 2.0 GeneChips with 47,000 probesets. Results: Eleven pts with CTCL have been entered to date. Two of the pts attained a complete response (CR), 3 attained a partial response (PR), 2 achieved stable disease (SD) with ongoing improvement, and 4 progressed on treatment (PD). Of particular interest, 2 pts who were initially SD required discontinuation because of toxicities (Grade III diarrhea at week 4, Grade II fatigue at week 12). Both had ongoing improvement in their disease achieving a CR and PR, respectively 3 months later. Of the 5 responding pts, one with a CR (discontinued after 10 doses due to Grade III diarrhea) progressed at 8m. Microarray data on the first 3 pts (2CR and 1PD) demonstrated distinct gene expression response profiles between the 3 pts. Surprisingly, the pt with PD showed the greatest transcriptional response with more than 16,000 genes activated or repressed over the 24 hr time course. Of these responsive genes, close to 60% were activated while 40% were repressed. In contrast, less than 1000 genes showed a 2-fold change in expression in the 2 pts with a CR with greater than 85% of the genes being repressed. Conclusions: LBH589 induce CR’s in CTCL pts. Regression of disease can occur some weeks after discontinuation of therapy. Preliminary microarray analysis of tumor samples indicated that LBH589 mediates changes in gene expression in vivo with an unexpected observed inverse relationship between the number of genes altered and clinical outcome. [Table: see text]
Altered Peripheral B-Lymphocyte Subsets in Type 1 Diabetes and Latent Autoimmune Diabetes in Adults
Authors: Chao Deng, Yufei Xiang, Tingting Tan, Zhihui Ren, Chuqing Cao, Gan Huang, Li Wen, Zhiguang Zhou
Journal: Diabetes Care (2015)

OBJECTIVE B lymphocytes play an important role in the immunopathogenesis of autoimmune diabetes. We hypothesized that the altered B-cell subset phenotype is associated with autoimmune diabetes. RESEARCH DESIGN AND METHODS Patients with type 1 diabetes (T1D) (n = 81), latent autoimmune diabetes in adults (LADA) (n = 82), or type 2 diabetes (T2D) (n = 95) and healthy control subjects (n = 218) with normal glucose tolerance (NGT) were recruited. We determined the percentage of circulating B-lymphocyte subsets, including CD19+CD23−CD21+ (marginal zone B [MZB]), CD19+CD23+CD21− (follicular B [FoB]), and CD19+CD5+CD1dhi (interleukin-10–producing regulatory B [B10]) cells by flow cytometry. RESULTS Patients with T1D or LADA had increased percentages of MZB cells and decreased percentages of FoB cells compared with healthy control subjects with NGT and patients with T2D. Moreover, patients with T1D showed the lowest frequency of B10 cells compared with patients with LADA or T2D, whereas healthy control subjects expressed the highest frequency of B10 cells. Of note, the frequency of MZB cells was negatively associated and the frequency of FoB cells was positively associated with fasting C-peptide (FCP). The frequency of B10 cells was positively correlated with FCP and negatively correlated with hemoglobin A1c. CONCLUSIONS The data show that patients with T1D or LADA express an altered frequency of B-cell subsets, which is associated with islet function and glycemia. These findings suggest that B lymphocytes may be involved in loss of self-tolerance and β-cell destruction and could be used as a biomarker and potential target for immunological intervention.
Reproductive risk factors of breast cancer in elderly population. A single centre study
Authors: D. Torregrosa, R. Gironés, P. López, R. Díaz Beveridge, I. Maestu
Journal: Journal of Clinical Oncology (2007)

21187 Background: Relationship between reproductive variables and cancer risk has been yet established. Protective effect of late age at menarche (≥ 11) and high parity (≥ 4) and the increased risk of nulliparous women, older age at first birth (AFB) (≥ 28) and older age at menopause (≥ 52) seems to act differently in pre vs. postmenopausal elderly women. The aim of this study was to describe recognized reproductive risk factors for breast cancer in a selected population of a single centre. Methods: A cross- sectional study of women diagnosed ≥ 70 years. We selected women with removed early breast cancer and on follow-up. No disease recurrences were allowed. Between January 2005 to June 2006. Described reproductive risk factors for breast cancer were collected. Tumour characteristics also. Results: 91 patients were recruited. Mean age at time of diagnosis: 76 (70–92); mean age at study 80 (71- 95). Reproductive factors: late age at menarche (12; 9–16; percentile 75: 14) and late age at menopause: 48 (29–56); 75% ≥ 52 years old were common. Nulliparous women were similar at described in other series (10%); parity 2 (0–9); percentile 75: 3;late AFB: 26 (19–40); percentile 75: 29 years. No one had taken hormonal treatment. Only 16% had familiar history of breast cancer and 9% personal history. Almost all (84%) had positive tumours for the oestrogen receptor and 76% for progesterone receptor. 91% had ductal histology and 54% had II stage. Conclusions: Discussion: unexpected associations between classical reproductive risk factors and breast cancer on elderly patients have been described in other series. It seems that late age at menarche and late age at menopause is common in elderly breast cancer population, as in our serie. Nulliparous elderly continue to have risk but seems that the protective effect of parity dissipated in these population. Older age at first birth (≥28) is consistently associated with increased breast cancer risk. Conclusion: our study is based on a high selected population and clearly has a selection bias. Our results cannot be generalized to other populations but describes our patients. The results therefore should be internally valid. And it seems to coincide with other studies. No significant financial relationships to disclose.
Laser treatment opens temporary window in blood-brain barrier
Authors: Jacqui Wise
Journal: BMJ (2016)

A laser system used to kill brain tumours also temporarily disrupts the blood-brain barrier, allowing chemotherapy drugs to pass into the brain for up to six weeks, finds a study published in PLoS One .1 The discovery may give doctors a window of opportunity to use drugs against glioblastoma that are normally ineffective, the researchers said.

Glioblastoma is the most common and lethal malignant brain tumour in adults. There is no effective long term treatment, and patients usually live for …
Variation in 5-hydroxymethylcytosine across human cortex and cerebellum
Authors: Katie Lunnon, Eilis Hannon, Rebecca G. Smith, Emma Dempster, Chloe Wong, Joe Burrage, Claire Troakes, Safa Al-Sarraj, Agnieszka Kepa, Leonard Schalkwyk, Jonathan Mill
Journal: Genome biology (2016)

The most widely utilized approaches for quantifying DNA methylation involve the treatment of genomic DNA with sodium bisulfite; however, this method cannot distinguish between 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). Previous studies have shown that 5hmC is enriched in the brain, although little is known about its genomic distribution and how it differs between anatomical regions and individuals. In this study, we combine oxidative bisulfite (oxBS) treatment with the Illumina Infinium 450K BeadArray to quantify genome-wide patterns of 5hmC in two distinct anatomical regions of the brain from multiple individuals. We identify 37,145 and 65,563 sites passing our threshold for detectable 5hmC in the prefrontal cortex and cerebellum respectively, with 23,445 loci common across both brain regions. Distinct patterns of 5hmC are identified in each brain region, with notable differences in the genomic location of the most hydroxymethylated loci between these brain regions. Tissue-specific patterns of 5hmC are subsequently confirmed in an independent set of prefrontal cortex and cerebellum samples. This study represents the first systematic analysis of 5hmC in the human brain, identifying tissue-specific hydroxymethylated positions and genomic regions characterized by inter-individual variation in DNA hydroxymethylation. This study demonstrates the utility of combining oxBS-treatment with the Illumina 450k methylation array to systematically quantify 5hmC across the genome and the potential utility of this approach for epigenomic studies of brain disorders.
A problem-oriented system approach to analysis of treatment outcome
Authors: H Klonoff, B Cox
Journal: American Journal of Psychiatry (1975)

Data on 90 psychiatric patients' perceptions of the course and outcome of hospitalization were gathered using a problem-oriented system. Patients were interviewed on admission, at discharge, and at two follow-up intervals. Therapists perceptions of patients' problems and their severity were also assessed on patients' admission and at discharge. Although the absolute number of problems reported by patients increased over time, there was a significant decrease over time, there was a significant decrease in the level of distress associated with problems on both patients' and therapists' ratings. The dynamics of this improvement are discussed from the perspectives of both patients and therapists.
Cancer Procoagulant and Tissue Factor Are Differently Modulated by All-trans-Retinoic Acid in Acute Promyelocytic Leukemia Cells
Authors: A. Falanga, R. Consonni, M. Marchetti, G. Locatelli, E. Garattini, C. Gambacorti Passerini, S.G. Gordon, T. Barbui
Journal: Blood (1998)
Evaluation of the importance of bronchoscopy in the intensivecare units
Authors: Jana Skřičková, Lenka Babičková, Anna Hrazdirová, Jana Koptíková, Adam Svobodník, Ilona Binková, František Salajka, Marcela Tomíšková
Journal: European Respiratory Journal (2003)

On the basis of 408 bronchoscopies done at the ICU the authors
prove the usefulness of bronchosocpy for diagnosis and
treatment of pulmonary complications in ICU patients.
Survival of 410 patients (pts) with solid tumors following high-dose chemotherapy (HDCT): A single center experience on 650 autologous haematopoietic stem-cell transplantation
Authors: P. Saintigny, J.-P. Lotz, F. Selle, J. Gligorov, S. Provent, A. Saavedra, T. Nakry, L. Bertheloot, V. Izrael
Journal: Journal of Clinical Oncology (2004)

6663 Background: HDCT in solid tumors is under evaluation. Methods: We report the survival of 410 pts treated between 1987 and 2002 in Tenon Hospital, including 99 germ cell tumors (GCT), 80 ovarian carcinomas (OC), 136 breast carcinomas (BC). OC and BC were mostly treated in partial or complete response (CR) to initial chemotherapy (iCT). GCT were mostly in progression to iCT. HDCT regimens were ICE or ICT (ifosfamide, carboplatine and étoposide or teniposide) and CMA (cyclophosphamide, mitoxantrone, melphalan) for GCT, OC and BC, respectively. Most GCT and OC received 2 or 3 HDCT. Results: Toxic death rate has reduced from 10% to 2% between 87–02. For GCT (median follow-up-(mFU):68 months (m)), 5-year overall survival (OS) rate was 68% in case of response, and 20% in case of progression to iCT. For OC (mFU:113 m), 5-year progression-free survival and OS rates were 30% and 32% in pts in response to iCT, 4% and 16% in pts in progression to iCT respectively. Prognostic impact of HER2 expression was evaluated in 45 pts with BC: in univariate analysis, HER2 overexpression was associated with a poorer OS (p=0.0085) and PFS (p=0.0122). For 68 metastatic BC (mFU:67 m), 5-year OS rate was 30% in pts in CR to iCT. In univariate analysis, factors associated with a poor OS were: progression to iCT (p=0.0001), recurrent disease (p=0.009) and negative hormonal receptors (p=0.04). In multivariate analysis, response to iCT (Relative risk (RR)=0.4;95%CI=0.19–0.96; p=0.04) and recurrent disease (RR=8.1;95%CI=1.4–46; p=0.01) were the only independent prognostic factors for OS in metastatic BC. Conclusions: Among progressive GCT, 20% were long-term survivors. Among responding OC, 30% were long-term survivors. For MBC, evaluating HDCT according to HER2 expression seems important. These results encourage randomised trials evaluating HDCT in pre-selected pts. No significant financial relationships to disclose.
Impact of microsatellite instability in overall survival of women with endometrial cancer.
Authors: J. C. Rocha, C. B. Chaves, V. P. Leite, F. C. Moreira, D. M. Ramalho
Journal: Journal of Clinical Oncology (2010)

5025 Background: Genetic alterations in DNA mismatch repair (MMR) genes cause microsatellite instability (MSI). MSI is a primary feature of HNPCC; in some sporadic tumors it is result of the silencing of MMR genes by methylation. Although a number of studies have correlated MSI with better outcomes in colon cancer, the impact of MSI in endometrial adenocarcinoma (EC) has been poorly explored. In this study, we assessed the relevance of MSI status in overall survival (OS) of pts with the diagnosis of EC from 2000 to 2003 in a single institution. Methods: A total of 395 pts were selected; out of these, 231 pts were considered eligible for the study after histologic review, and tissue blocks recovery. DNA was extracted from paraffin embedded tumor and normal tissue and six different microsatellite regions (BAT-25, BAT-26, D2S123, D5S346, D17S250 and BAT-40) were amplified by PCR. PCR product sizing and MSI identification was performed using the Agilent 2100 Bioanalyzer platform. Tumors were classified as MSS when all markers were stable, as MSI-L when only one marker was unstable, and as MSI-H when at least two markers were unstable. Results: The median age was 64 (25-90yo). PCR and MSI analysis were successful in 97.4% of the cases; 186 out of 225 tumors, were classified as type I (82.7%), 32 tumors were type II (14.2%), and 7 were inconclusive and classified as others. According to FIGO staging criteria, 137 pts (60.9%) were stage I; 47 (20.9%) stage II; 36 (16%) stage III; 5 (2.2%) stage IV. MSI was found in 75 pts (32.5%). Among those with type I subtype, MSI was presented in 64 pts (34.4%) and in 32 pts with type II (14.2%). No significant difference in OS was found between MSI-L and MSI-H after Fisher's Exact Test, therefore tumors with any MSI status were joined for further comparisons. FIGO lower stages (p = 0.006), type I subtype (p = 0.032), and MSI (p = 0.007) were prognostic for longer OS (univariable analysis). Cox regression was used for multivariable analysis, and MSI status sustained significant after adjustment for other variables (p = 0.013). Conclusions: MSI was an independent prognostic factor for EC in this retrospective study. Together with other relevant characteristics could be used as a molecular marker for the prediction of OS. No significant financial relationships to disclose.
ROR1 functions as a scaffold of cavin-1 and CAV1, sustaining caveolae and RTK-mediated survival signaling in lung cancer
Authors: Tomoya Yamaguchi, Can Lu, Lisa Ida, Kiyoshi Yanagisawa, Jiro Usukura, Jinglei Cheng, Naoe Hotta, Yukako Shimada, Hisanori Isomura, Motoshi Suzuki, Toyoshi Fujimoto, Takashi Takahashi
Journal: Journal of Thoracic Oncology (2016)
Strike action looms again as talks over junior doctors’ contract stall
Authors: Jacqui Wise
Journal: BMJ (2015)

Talks between the UK government and junior doctors over their new contract stalled before Christmas, with two areas of absolute disagreement still remaining. If there is no further progress when talks resume in the New Year, then industrial action is looking likely to be scheduled for 13 January.

Johann Malawana, chair of the BMA’s Junior Doctors Committee, wrote in a post on the BMA website on 24 December: “Whilst significant ground has been made, and JDC [the Junior Doctors Committee] has worked extremely hard within certain constraints set out from the government, there are still a couple of absolute areas of disagreement. These are born out as being two …
Comparison of cervical flora in patients with carcinoma cervix on external radiation therapy using water, povidone-iodine or lactic acid as douche solutions
Authors: S. S. John
Journal: Journal of Clinical Oncology (2004)

5093 Introduction: Cervical cancer is the commonest malignancy in India. Most cases present with advanced stage disease hence they are treated with radiotherapy during which they are advised to undergo self vaginal douche. In this prospective, randomized, 3 arms study we have used water, povidone-iodine and lactic acid douche solutions and evaluated hygiene by assessing cultures taken of cervical swabs. Material and methods: The aim of the study was to see any change in the cervical flora after using different douche solutions. The inclusion criteria consisted of patients with FIGO stage IIA to IIIB on radical external radiotherapy who had squamous cell carcinoma of the cervix. From May 2001 to May 2002 we selected 64 consecutive patients who were eligible and advised them to undergo self douche with either water, povidone-iodine or lactic acid. A cervical swab was taken at 0, 20 and 40 Gray(Gy) and an aerobic culture was carried out. The patients received 46 to 60 Gy of external radiation therapy following which they underwent brachytherapy. Results: The median age of the patients was 48.5 years (range 30–85). 22 patients did douche with water, 22 with povidone iodine and 20 with lactic acid. At 0 Gy there were 5 positive cultures with patients on water, 7 with patients on povidone-iodine and 4 with patients on lactic acid. At 20 Gy there were 8 positive cultures with patients on water, 6 with patients on povidone-iodine and 2 with patients on lactic acid. At 40 Gy there were 6 positive cultures with patients on water, 5 with patients on povidone-iodine and 2 with patients on lactic acid. Conclusions: 25 patients had no growth in either of the 3 cultures and 34 patients had grown aerobic organisms. The commonest organism was Klebsiella aeroginosa grown in 24 cultures. 11 cultures grew E.coli and staphylococcus pyogenes, 5 pseudomonas pyocyneae and 2 streptococcus fecalis. Out of the 34 patients 20 had just one positive culture, 11 had 2 positive cultures and 3 had growth in all 3 cultures. There was a decrease in the intensity of growth from heavy to moderate after initiation of douche. No significant financial relationships to disclose.
Neighborhood strain and adaptation factors as multilevel predictors of mammography use among African American and Latina women across Chicago neighborhoods
Authors: R. Massenburg, I. Safika, E. A. Calhoun
Journal: Journal of Clinical Oncology (2008)

1544 Background: Minority women have lower rates of mammogram use and die from breast cancer at a disproportionate rate (Peek, 2007). It has also been noted that there is a relative shortage of free and low cost mammography services in the most underserved areas across Chicago (Zenk et al., 2006). As one would expect this differential in access contributes to the breast caner mortality disparity (Hirschman et al., 2007). The Reach Out 2010 project is an intervention designed to address this health disparity by providing mammography intervention through education and financial assistance. Data from the study found that differences exist between African American women and Latino women breast cancer screening behavior, but there has been no evaluation of neighborhood level variation (Darnell, 2006). Methods: This article used data from the Reach 2010 project, psychological theories and hierarchical modeling of both individual behavior and neighborhood factors to understand how to more effectively eliminate mammography related disparities. Results: Analyzing 729 women from 22 Chicago zip codes we found that 1) mammogram use varied by across neighborhoods; 2) individual characteristics—talking to doctor about breast cancer, age, high income—were all positively associated with mammogram use; recency of doctor's visit was negatively associated with mammogram use; 3) population density and percent African American population of a zip code were negatively and positively, respectively, associated with mammogram use; and 4) that population density community where individual had low income and recent doctor's visits without talking about breast cancer were less likely to have a mammogram. Conclusions: This article has shown that breast cancer screening behavior is a multi-level phenomenon that involves both individual characteristics and neighborhood factors. Future mammography interventions would be better well to focus on highly populated areas. There may also be some benefit to reallocating resources in such a way that allows better access to low resourced areas. No significant financial relationships to disclose.
Liposomal doxorubicin in sequential doublet combination with paclitaxel and carboplatin in patients with primary epithelial ovarian or primary peritoneal carcinoma
Authors: M. W. Method, M. Rodriguez
Journal: Journal of Clinical Oncology (2004)

5094 Background: This Phase I trial will evaluate liposomal doxorubicin (Doxil) in a sequential-doublet in Primary Ovarian CA. Materials: Patients with EOC or PPC, Stage IIB - IV following initial surgery were eligible. Treatment: PEG-A at dosing from 35–45mg/m2 with Carboplatin AUC 6.0–5.0 for 4 cycles every 28 days followed by Paxlitaxel at 175mg/m2/3hr with Carboplatin AUC 6.0–5.0 for 4 cycles every 21 days. Complete WHO toxicities were recorded with toxicity parameters for PPE, thrombocytopenia, and SAE's. Results: Enrolled: 11 ovarian and 2 peritoneal CA. 12/13 were stage III or IV with all optimally cytoreduced. 12/13 completed treatment as planned. 6 received Carboplatin AUC 6.0, 4 @ 35mg/m2 and 2 @40mg/m2 of PEG-A followed by Paclitaxel 175mg/m2 and Carboplatin AUC 6.0. 3/6 had grade 2–3 platelet toxicities at cycle 7 and/or 8 with delay. Carboplatin was reduced to AUC 5.0 x 8 cycles for the next 7; 4 @ 40mg/m2 and 3 @ 45mg/m2 PEG-A x 4 followed by paclitaxel combination. 2 @ 45mg/m2 had Grade I PPE and 1 @ 45mg/m2 had grade 3 PPE after the 4th. No other had PPE and no other non-hematologic toxicity greater than grade I was observed with 4 cycles of PEG-A and Carboplatin. Grade II –III hematologic toxicity was common without treatment delay or morbidity except Carboplatin dosing @ AUC 6.0. All experience grade II alopecia after 2 cycles of Paclitaxel combination. 6/13 experience grade I neurosensory toxicity following 8 cycles of treatment with no reported grade 2 or 3 neurotoxicity. Mean pre-surgical CA-125 was 1448 (SD: 1324). Mean CA-125 following 4 cycles of PEG-A + Carboplatin was 31.87 (SD: 33). All achieved a clinical complete remission following 8 cycles of therapy with mean CA-125 of 18.9 (SD: 7). Conclusion: Optimal dosing of this sequential doublet: PEG-A @ 40mg/m2 + Carboplatin AUC 5.0 x 4 every 28 days followed by Paclitaxel @ 175mg/m2/3hr + Carboplatin AUC 5.0 x 4 every 21 days. Minimal non-hematolgic toxicity and no alopecia during the initial 4 cycles of treatment; hematologic toxicity was manageable without factor. 25% more anthracycline was possible compared to the triplet approach with minimal neurotoxicity. Efficacy appears favorable. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline; Wyeth Ortho Biotech