tbuckley/cabot-search huggingface dataset:
Myeloid-derived suppressor cells absolute counts in predicting durable response to R-CHOP in patients with follicular lymphoma.
Authors: V. Pitini, M. Santarpia, C. Tomasello, C. Arrigo, G. Marabello, M. G. Sauta, S. Loddo, G. Barresi, G. Altavilla
Journal: Journal of Clinical Oncology (2011)

e18504 Background: High amounts of CD68+ macrophages in tumor micro-environment (TAM) have been shown to correlate with prognosis in pts. with follicular lymphoma (FL). In order to identify an additional marker with prognostic significance we evaluated the circulating levels of myeloid derived suppressor cells (MDSC) which are the putative progenitors in the peripheral blood of TAM in 68 FL pts treated with R-CHOP who have had follow-up for at least 30 months. Methods: Circulating levels of MDSC identified as CD34+, CD45+, CD116+, CD13+, CD14- were evaluated by flow cytometry. Immuno-histochemistry for CD68 was performed on tissue sections. PFS and OS were calculated according to the Kaplan-Meier method. Results: 33 male, 35 female, mean age 56.1 years (20 FL grade 1; 32 grade 2, 16 grade 3A) were included in the analysis. All pts. were treated with R-CHOP in the front line (46/68) or the first relapse (22/68) and all pts. received R for the first time. The analysis of the circulating levels of MSDC showed two different patterns. 40/68 pts had higher levels of circulating MDSC when compared to 30 healthy controls (mean 3.91/mmc vs 1.60/mmc, p= 0.0001) coinciding with high amounts of TAM, 28/68 pts had lower MDSC levels (mean 1.71/mmc) which were correlated to a low number of TAM. The median PFS was not reached for pts. with high MDSC absolute count compared with 21 months for pts. with lower circulating MDSC. A trend towards a better OS at 30 months was also observed for pts. with high MDSC content (OS, 97% versus 92%). Conclusions: Our findings favor the hypotesis that macrophages may act synergically with anti-CD20 targeted therapy perhaps enhancing the antibody-dependent cellular cytotoxicity of R. Furthermore, this mechanism could explain the diminished beneficial effect of rituximab in pts. with low MDSC.
Regional isolated limb perfusion of melanoma intransit metastases using mechlorethamine (nitrogen mustard).
Authors: M H Shiu, W H Knapper, J G Fortner, S Yeh, G Horowitz, J Schnog, J Guerra, P Gould-Rossbach, C Ray
Journal: Journal of Clinical Oncology (1986)

Forty-two patients with intransit metastases of melanoma in a limb were treated by isolated regional perfusion chemotherapy using mechlorethamine (nitrogen mustard). Group 1 (n = 12) underwent treatment at low dose, less than 0.35 mg/kg, or low temperature, less than 38 degrees C. Group 2 (n = 30) received higher doses, 0.35 to 0.6 mg/kg, plus heat at 38 degrees C to 41 degrees C. No patient had evidence of disease outside the limb at the time of perfusion. The median follow-up time was 48 months (range, 1 to 9 years). Of the 42 patients, 29 had measurable lesions that responded as follows: group 1, complete response (CR) in two of ten and partial response (PR) in none; group 2, CR in six of 19 and PR in six of 19. The combined CR and PR rate of 12 of 19 in group 2 was significantly higher than that of group 1 (P less than .05). CR lasted only 2 months in the two patients of group 1, but persisted in the six patients of Group 2, four of whom are still alive free of disease at 16, 21, 33, and 40 months. Relapse-free control of disease in the limb was achieved in 36% of the patients in group 2 at 24 months, compared with 0% in group 1 (P less than .05). An overall survival of 74% at 48 months was observed in group 2, significantly higher than that of 64% for group 1 (P less than .05). The status of the regional lymph nodes (RLN) and the number of metastases did not affect tumor response. However, 77% of RLN-negative patients survived 48 months, in contrast to only 38% of RLN-positive patients (P less than .05). One patient died postoperatively of myocardial infarction. No serious systemic toxicity developed. Two patients who underwent repeat salvage perfusions developed a reversible peripheral neuropathy in the limb. Limb function was good after treatment, and dramatically improved in patients who had advanced satellitosis that responded to treatment. These results suggest that heated limb perfusion using mechlorethamine at an adequate dose can offer long-term control of intransit metastases in approximately one third of these patients, with preservation of good limb function and possible prolongation of survival.
Biomarkers predictive for pathologic response to neoadjuvant docetaxel/cyclophosphamide chemotherapy in primary breast cancer.
Authors: Kazuhiro Shimada
Journal: Journal of Clinical Oncology (2013)

42 Background: Since docetaxel /cyclophosphamide chemotherapy (TC) has proven to be superior to anthracycline/cyclophosphamide (AC) in U.S. Oncology Research Trial 9735, TC has been widely used for treating patients with breast cancer. However, taxane-specific adverse events like neuralgia and edema can’t be ignored. Thus, we performed neoadjuvant study with TC to clarify biological markers of this regimen. Methods: 79 patients with invasive breast cancer received TC (docetaxel 75 mg/m2, cyclophosphamide 600 mg/m2, q3w for 4 courses) at the neoadjuvant setting and underwent surgical treatment. Before treatment, the clinic-pathological and immunohistochemical markers (ER, PgR, HER-2, Ki-67, p53, topoisomerase IIα, ClassIII β tubulin, CK5/6, EGFR) were examined with core-needle biopsy specimens. The correlation between the pathological response and expressions of markers was investigated. Results: 33 patients (41.8%) achieved quasi-pathological complete response (QpCR). Univeriate analysis revealed that ER (p &lt; 0.001), PgR (p = 0.007), Ki-67 (p = 0.022) and classIII β tubulin (p = 0.032) were associated with QpCR. Only ER (p = 0.050) and classIII β tubulin (p = 0.028) remained with a statistical significance at multivariate analysis. Subgroup analysis revealed that the negativity of CK5/6 and/or EGFR was correlated with QpCR in the triple negative subtype. Conclusions: ClassIII β tubulin had a specific predictive value for pathological response of TC in addition of ER, PgR and Ki-67. Sub-grouping is important for treating triple-negative breast cancer.
Antithrombin III inhibits mesangial cell proliferation.
Authors: M V Pahl, N D Vaziri, F Oveisi, J Wang, Y Ding
Journal: Journal of the American Society of Nephrology (1996)

Thrombin stimulates and heparin and heparan sulfate inhibit mesangial cell proliferation. In addition, heparin has been shown to inhibit thrombin-stimulated smooth muscle cell proliferation. The anticoagulant action of heparin is mediated by antithrombin III. This study investigated whether heparin's antiproliferative action is also mediated by antithrombin III. To this end, the effect of antithrombin III on thrombin-stimulated mesangial cell growth was examined. As expected, thrombin stimulated DNA synthesis and cell growth in cultured human mesangial cells. The effect of thrombin on DNA synthesis and mesangial cell proliferation was inhibited by standard heparin and antithrombin III, separately or together. The magnitude of the inhibitory action of antithrombin III was equal to that of equimolar concentrations of heparin and that observed with the combination of the two. Experiments carried out in serum (hence antithrombin III)-free medium revealed that heparin's inhibitory effects are independent of antithrombin III. It was concluded that antithrombin III, an endogenous inhibitor of thrombin's coagulant activity, is an equally effective inhibitor of thrombin's mitogenic action.
Sabina Jeannette Strich
Authors: David W Millard
Journal: BMJ (2016)

Sabina Jeannette Strich was born in Munich into an intellectual Jewish family who forestalled persecution by moving initially to Italy and finally Cambridge. She attended a boarding school in Holland and the Perse School, Cambridge, from which she obtained a scholarship to Lady Margaret Hall. After qualifying she joined the Oxford pathology department as a research officer in neuropathology under Professor Peter Daniel, whom she followed to the Maudsley …
Results of the SPACE FOR COPD programme in comparison to pulmonary rehabilitation at 6 months
Authors: Elizabeth Horton, Katy Mitchell, Vicki Johnson-Warrington, Lindsey Apps, Hannah Young, Sally Singh
Journal: European Respiratory Journal (2014)

Home based self management (SM) rehabilitation programmes for patients with COPD offer an alternative to pulmonary rehabilitation (PR). There is a lack of evidence of such programmes and furthermore how effective they are in maintaining change compared to PR. We have developed a manual based SM programme for patients with COPD and aim to assess the effectiveness of the SPACE for COPD programme at 6 months.

145 patients (95 males: mean (SD) age 68 (9) yrs; FEV1 pred 47% (18%)) with COPD were randomised to SPACE or PR. Those in the SPACE group received an introduction to SPACE and 2 telephone calls. PR received 14, 2 hour sessions of education and exercise over 7 weeks. The primary outcome was Chronic Respiratory Questionnaire (CRQ) dyspnoea, with secondary measures of Hospital Anxiety and Depression Scale (HADS), Incremental Shuttle Walk Test (ISWT) and Endurance Shuttle Walk Test (ESWT). Analysis is presented for HADS of those scoring ≥8 at baseline. Measures were taken at baseline, 7 weeks and six months. A Repeated measures ANOVA was conducted.

Results. See table 1.

View this table:



The SPACE FOR COPD programme improves dyspnoea, anxiety and endurance time which are maintained at 6 months. There are no differences in outcome measures at 6 months between SPACE and PR groups.
Abstract P216: Blood Pressure Level as Predictor for Developing Diabetes Type 2
Authors: Christina Stahl-Heden@, Lena M Bjorck, Masuma Novak, Wai Giang Kok, Per-Olof Hansson, Annika Rosengren
Journal: Circulation (2012)

Introduction and Aim: The link between diabetes type 2 and hypertension is a well established with both factors parts of the metabolic syndrome. Whether hypertension is an independent predictor for diabetes type 2 development has been examined in previous studies, however with divergent findings. The aim of this study was to investigate whether hypertension, including mildly elevated blood pressure within the normal range predicted subsequent development of diabetes type 2 over an extended follow-up. Methods and Results: Data were derived from participants of the intervention group of the Gothenburg primary prevention study where a random sample of 7333 men aged 47-55 years and free of diagnosed diabetes underwent a screening investigation in 1970 to 1973. During a 32-year follow-up, 956 men (13%) were diagnosed with diabetes according to the Swedish hospital discharge register. Development of diabetes type 2 was positively correlated to age, BMI, systolic blood pressure (SBP) and diastolic blood pressure (DBP), serum cholesterol, hypertension treatment, non-manual occupation, high tobacco use, sedentary lifestyle at the midlife screening. In a Cox regression model which adjusted for BMI and other risk factors we calculated the multiple adjusted hazard ratio for developing diabetes type 2 according to blood pressure level. Compared to a reference level of systolic blood pressure (SBP) below 130 mm Hg, men with SBP of 130-139 mmHg, 140-149 mmHg and &gt; 150 mmHg had a multiple adjusted hazard ratios (HRs) of 1.41 (95% confidence interval) 1.11–1.80), 1.38 (1.08–1.75) and 1.67 (1.35–2.07), respectively. Mid-life diastolic blood pressure over 90 mmHg was associated to an increased risk of developing diabetes type 2 (multiple adjust HRs of 1,60 1,21–2,11) Conclusion: In this population, at mid-life, hypertension as well as moderately elevated systolic blood pressure levels within the normal range was shown to be independent predictors of diabetes type 2.
A non-invasive urine-based research test for the detection of prostate cancer using DNA methylation
Authors: Tatiana Vener, Carlo Derecho, Shobha Varde, Abhijit Mazumder, Madeleine Grooteclaes, Katja Bierau, Joost Louwagie, Joseph Bigley, Laurence de Leval, Jean de Leval, Yves Gaspar, Luc Coppens, David Waltregny
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

3502 

Introduction : The best outcome for patients with prostate cancer (PCa) is seen for those treated at an early stage of the disease. A digital rectal examination (DRE) and the measurement of serum prostate specific antigen (PSA) levels are the current standards for PCa early detection. However, serum PSA testing lacks both sensitivity and specificity, and core biopsies frequently fail to identify small foci of PCa. The availability of non-invasive diagnostic molecular tests that could allow for a more precise identification of malignant prostate cells in asymptomatic men would be of great clinical value to improve PCa diagnosis.

Study design : 114 men scheduled to undergo a prostate biopsy were enrolled in the study. The biopsies were triggered either by an abnormally high PSA value or by suspicious findings on DRE. Patients with other known or suspected urinary malignancy were excluded from the study. Morning, post-prostate massage and post-biopsy urine samples were collected from all individuals. The main goals of this study were a) to determine if prostate massage can improve the prostate DNA quantity compared to urine collected in the morning or after biopsy, and b) to evaluate the methylation status of a gene panel in urine samples from subjects with cancer found in prostate biopsy tissue cores versus subjects without cancer.

Methods : Gene promoter methylation is associated with prostate cancer and has been successfully used for the molecular detection of neoplasia in urine. We have developed real-time methylation specific PCR assays to define the methylation status of several genes.

Results : Median age of the patients was 65 years (range 48-85). PCa was found in 51% of the patients. Histological diagnosis of the biopsies was compared to methylation results in urine from 102 samples (89% success rate due low DNA yields for 12 samples). The comparison between different urine sampling techniques showed that prostate massage is needed. The best results were obtained in post massage urine samples with a combination of GSTP1, p14, p16, RARβ2 and RASSF1A resulting in a sensitivity of 74% and a specificity of 75%.

Future : A multiplex assay using the Cepheid SmartCycler™ II platform is under development. Further studies are in progress to validate the assay across multiple centers.
Burden of sickle cell trait and disease in the Uganda Sickle Surveillance Study (US3): a cross-sectional study
Authors: Grace Ndeezi, Charles Kiyaga, Arielle G Hernandez, Deogratias Munube, Thad A Howard, Isaac Ssewanyana, Jesca Nsungwa, Sarah Kiguli, Christopher M Ndugwa, Russell E Ware, Jane R Aceng
Journal: The Lancet Global Health (2016)

BackgroundSickle cell disease contributes substantially to mortality in children younger than 5 years in sub-Saharan Africa. In Uganda, 20 000 babies per year are thought to be born with sickle cell disease, but accurate data are not available. We did the cross-sectional Uganda Sickle Surveillance Study to assess the burden of disease.MethodsThe primary objective of the study was to calculate prevalence of sickle cell trait and disease. We obtained punch samples from dried blood spots routinely collected from HIV-exposed infants in ten regions and 112 districts across Uganda for the national Early Infant Diagnosis programme. Haemoglobin electrophoresis by isoelectric focusing was done on all samples to identify those from babies with sickle trait or disease.FindingsBetween February, 2014, and March, 2015, 99 243 dried blood spots were analysed and results were available for 97 631. The overall number of children with sickle cell trait was 12 979 (13·3%) and with disease was 716 (0·7%). Sickle cell numbers ranged from 631 (4·6%) for trait and 23 (0·2%) for disease of 13 649 in the South Western region to 1306 (19·8%) for trait and 96 (1·5%) for disease of 6581 in the East Central region. Sickle cell trait was seen in all districts. The lowest prevalence was less than 3·0% in two districts. Eight districts had prevalence greater than 20·0%, with the highest being 23·9%. Sickle cell disease was less common in children older than 12 months or who were HIV positive, which is consistent with comorbidity and early mortality.InterpretationPrevalence of sickle cell trait and disease were high in Uganda, with notable variation between regions and districts. The data will help to inform national strategies for sickle cell disease, including neonatal screening.FundingCincinnati Children's Research Foundation.
Adenosine Triphosphate: Does It Help Cancer Patients “Get Bigger and Stronger”?
Authors: Aminah Jatoi, Charles L. Loprinzi
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.2.362 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11786561 Adenosine Triphosphate: Does It Help Cancer Patients “Get Bigger and Stronger”? Aminah JatoixAminah JatoiSearch for articles by this author , Charles L. LoprinzixCharles L. LoprinziSearch for articles by this author Show More Mayo Clinic, Rochester, MN https://doi.org/10.1200/JCO.2002.20.2.362 Full Text PDF Figures and Tables "Adenosine Triphosphate: Does It Help Cancer Patients “Get Bigger and Stronger”?." Journal of Clinical Oncology, 20(2), pp. 362–363© 2002 by American Society of Clinical Oncology
Abstract 4344: Olfactomedin 4 plays a tumor-suppressor role and is a novel candidate biomarker in the prostate cancer progression and independent of PSA
Authors: Hongzhen Li, Ye Chen, Wenli Liu, Jianqiong Zhu, Chin Kay, Xujing Wang, Griffin P. Rodgers
Journal: Cancer Research (2015)

Abstract Prostate cancer is the most commonly diagnosed solid tumor and the second leading cause of cancer-related death in the American male population. The olfactomedin 4 gene (OLFM4) plays critical tumor suppressor roles in human and murine prostate cancer. We have previously reported that loss or reduce of OLFM4 expression is associated with the progression of human prostate cancer. We further found that loss of Olfm4 leads to prostate neoplastic progression in the Olfm4-knockout mouse model. To study the clinical impacts of OLFM4 gene in the prostate cancer, we have performed bioinformatics analysis from the published datasets, GSE35988, GSE21032 and TCGA as well as immunohistochemical analysis with prostate cancer tissue arrays by using OLFM4 antibody. The copy number variations (CNV) of OLFM4 gene were significantly associated with Gleason scores of prostate cancer. The pattern of OLFM4 CNV is similar with other tumor suppressor genes, RB1, PTEN and P53. We have observed consist reduce or loss of mRNA expression in the castrate resistant and metastatic prostate cancer patient samples. To study the relationship between OLFM4 expression and prostate cancer recurrence, we performed Kaplan-Meier Plots and Log-rank statistic analysis for GSE21032 and TCGA data sets. Overall, there was no significant relationship between OLFM4 expression and prostate cancer recurrence. However, when analysis was restricted to the lower quartile of OLFM4 expression, we obtained a highly significant inverse relationship (p = 0.02) between OLFM4 expression and recurrence. We also observed that alteration of CNV and expression of OLFM4 gene has no relationship with the level of (patient) serum prostate specific antigen (PSA). We performed immunohistochemical analysis with prostate cancer tissue arrays by using OLFM4, PSA and E-cadherin antibodies. Lower or loss of expression of OLFM4 protein is associated with advanced Gleason scores of prostate cancer specimens. The pattern of OLFM4 protein expression in prostate cancer patient samples is similar to that of E-cadherin, but not PSA. Taken together, these results suggest that OLFM4 plays a tumor-suppressor role, and therefore is a likely therapeutic target for prostate cancer interdiction. Citation Format: Hongzhen Li, Ye Chen, Wenli Liu, Jianqiong Zhu, Chin Kay, Xujing Wang, Griffin P. Rodgers. Olfactomedin 4 plays a tumor-suppressor role and is a novel candidate biomarker in the prostate cancer progression and independent of PSA. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4344. doi:10.1158/1538-7445.AM2015-4344
Comparison of maximal exercise capacity between patients with COPD from Brazil and United Kingdom
Authors: Rafael Barreto de Mesquita, Carolyn Sandland, Nidia Aparecida Hernandes, Vanessa Suziane Probst, Sally Singh, Fábio Pitta
Journal: European Respiratory Journal (2011)

Background: Field exercise tests such as the incremental shuttle walking test (ISWT) have been used worldwide in order to assess exercise capacity of patients with chronic obstructive pulmonary disease (COPD). However, the responses to this test in patients from different world regions have not yet been compared.

Objectives: To compare the responses to the ISWT between patients with COPD from Brazil and United Kingdom (UK).

Methods: 20 patients with COPD from Brazil were matched to 20 patients from the UK concerning gender distribution, age, body mass index and FEV1. All patients performed the ISWT during the baseline assessment for admission to a pulmonary rehabilitation program in their respective country. The total distance walked was recorded and heart rate (HR), oxygen saturation (SpO2) and dyspnea score (Borg scale) were assessed before and after the test in both centers.

Results: In both groups, SpO2 decreased and HR and dyspnea scores increased significantly after the test (p<0.05 for all). Brazilian patients walked farther and achieved higher% of their maximal predicted HR than patients from the UK (345±173 vs 209±116 meters [p=0.006] and 80±12 vs 64±10%pred [p<0.0001], respectively). The increase in dyspnea sensation after the test tended to be higher in the Brazilian group (4 [2-6] vs 2 [1-4], p=0.06).

Conclusions: Brazilian patients with COPD seem to walk more and achieve higher effort during the ISWT than patients from the United Kingdom. This is in line with previous data showing that patients from South America (especifically Brazil) are more active in daily life and have better functional exercise capacity in comparison to patients from Europe and United States.