tbuckley/cabot-search huggingface dataset:
LSC 2014 abstract - Expansion of multiple dendritic cell populations in the alveolar parenchyma in patients with COPD
Authors: Michiko Mori, Cecilia Andersson, Medya Shikhagaie, Anders Bergqvist, Claes-Göran Löfdahl, Jonas Erjefält
Journal: European Respiratory Journal (2014)

Rationale: Recent data suggest that alveolar adaptive immune responses are important immunopathological features of COPD. The cellular basis for alveolar antigen uptake remains however poorly investigated, especially in human lungs. This study performs an extensive histological characterization of alveolar dendritic cell (DC) populations and explores if they are abnormally abundant, or phenotypically altered, in patients with COPD.  Methods: Double and triple immunohistochemistry for langerin, CD1a, BDCA-2, CD11c, CD68 and CD163 was performed on distal lung tissues from patients with mild, moderate-to-severe, and very severe COPD. Never-smoking and smoking non-COPD subjects served as controls.  Results: Four distinct subsets of alveolar DCs were quantified; langerin+, CD1a+ langerin-, BDCA-2+, and CD11c+ CD68- CD163- DCs. Increased numbers of alveolar CD1a+ langerin- (pl0.05) and BDCA-2+ DCs (pl0.001) were observed in advanced COPD compared with never-smoking and smoking controls. In addition, after exclusion of confounding macrophages, the area of alveolar CD11c+ CD68- CD163- immunoreactivity increased in advanced COPD (pl0.01). In the small airways, langerin+ and BDCA-2+ DCs were also significantly increased. Contrasting the small airway DCs, all alveolar DC subsets but BDCA-2+ frequently extended luminal protrusions. Importantly, alveolar and small airway langerin+DCs were phenotypically different and displayed site-specific marker profiles.  Conclusion: Multiple alveolar DC populations are expanded in advanced COPD and are likely to contribute to the aggravated distal adaptive immune responses in this disease.
Application of a Job-Exposure Matrix to a Case-Control Study of Lung Cancer&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M W Hinds, L N Kolonel, J Lee
Journal: JNCI Journal of the National Cancer Institute (1985)

Interview information was obtained on primary and secondary occupations for 261 male lung cancer patients and 444 controls residing on the island of Oahu, HI. With the use of a computerized job-exposure matrix (JEM), exposure levels were assigned to each subject for each of 5 known and 2 likely lung carcinogens. A multiple logistic regression model was used to compute the odds ratio (OR) for exposure to each carcinogen, adjusted for age, ethnicity, and pack-years of smoking. On the basis of the criterion of either a dose-response effect or a statistically significant OR (P less than .05) or both, 5 of the 7 carcinogens (4 of the 5 known carcinogens) were found to be associated with lung cancer risk. However, on the basis of the single criterion of a significant OR, only 3 of the 7 carcinogens (2 of the 5 known carcinogens) were associated with lung cancer risk. Due to its relative insensitivity, this JEM may have limited usefulness in the identification of exposure-disease relationships and should not be applied uncritically.
Dose intensity of MOPP chemotherapy and survival in Hodgkin's disease.
Authors: R E van Rijswijk, C Haanen, A W Dekker, A J de Meijer, J Verbeek
Journal: Journal of Clinical Oncology (1989)

The association between dose intensity of chemotherapy with the rate of complete remission (CR), the duration of disease-free survival (DFS), and overall survival (OS) was separately analyzed for 67 patients initially treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), and for 75 patients in relapse following radiotherapy who had received MOPP as a salvage regimen. In both groups of patients, the fraction of the total dose of mechlorethamine delivered in all cycles divided by the planned dose for six cycles was strongly associated with OS (P = .002 for patients receiving initial MOPP and P = .02 for the salvage group, respectively). B symptoms were independent of drug-derived variables associated with OS (corresponding P values .03 for initial MOPP and .004 for the salvage group). The predictive value of mechlorethamine dosage with regard to OS was retained in an analysis restricted to the patients receiving greater than or equal to six cycles of chemotherapy. In the initial chemotherapy group, mechlorethamine dosage was associated with attainment of CR but none of the variables tested was predictive of DFS. In the salvage chemotherapy group, mechlorethamine dosage was associated with attainment of CR and duration of DFS as well. The results emphasize that, besides tumor characteristics, optimal dosage of chemotherapy is of great importance for survival.
Ectopic bone formation in rapidly fabricated acellular injectable dense collagen-Bioglass hybrid scaffolds via gel aspiration-ejection
Authors: Amir K. Miri, Naser Muja, Neysan O. Kamranpour, William C. Lepry, Aldo R. Boccaccini, Susan A. Clarke, Showan N. Nazhat
Journal: Biomaterials (2016)
The Novel Synthetic Retinoid 6-[3-adamantyl-4-hydroxyphenyl]-2-naphthalene Carboxylic Acid (CD437) Causes Apoptosis in Acute Promyelocytic Leukemia Cells Through Rapid Activation of Caspases
Authors: Luca Mologni, Isabella Ponzanelli, Filippo Bresciani, Gabriele Sardiello, Daniele Bergamaschi, Maurizio Giannı́, Uwe Reichert, Alessandro Rambaldi, Mineko Terao, Enrico Garattini
Journal: Blood (1999)
Long-term Effects of Octreotide on Liver Volume in Patients With Polycystic Kidney and Liver Disease
Authors: Antonio Pisani, Massimo Sabbatini, Massimo Imbriaco, Eleonora Riccio, Nadia Rubis, Anna Prinster, Annalisa Perna, Raffaele Liuzzi, Letizia Spinelli, Michele Santangelo, Giuseppe Remuzzi, Piero Ruggenenti, A. Pisani, M. Sabbatini, P. Ruggenenti, G. Remuzzi, A. Pisani, B. Visciano, M. Amicone, R. Dipietro, G. Mozzillo, E. Riccio, R. Rossano, M. Sabbatini, L. Spinelli, M. Santangelo, N. Rubis, O. Diadei, W. Calini, A. Villa, M. Sabatella, B. Ene-Iordache, S. Carminati, D. Martinetti, G.A. Giuliano, A. Perna, R. Liuzzi, A. Remuzzi, M. Imbriaco, A. Prinster, M. Altiero, P. Boccardo, S. Peracchi
Journal: Clinical Gastroenterology and Hepatology (2016)
Biomarker analysis and final results of INT70/09 phase II proof-of-concept study of pazopanib (PZP) in refractory urothelial cancer (UC).
Authors: Andrea Necchi, Nadia Zaffaroni, Luigi Mariani, Lawrence H. Schwartz, Nicola Nicolai, Patrizia Giannatempo, Flavio Crippa, Carlo Morosi, Alessandro M. Gianni, Filippo G. De Braud, Roberto Salvioni
Journal: Journal of Clinical Oncology (2012)

4507 Background: Discouraging results have been achieved with standard and novel compounds in refractory UC. The final results with biomarker analysis of INT70/09 trial with pazopanib are presented. Methods: Pts failing ≥ 1 chemotherapy regimen for metastatic disease underwent PZP 800 mg once daily until PD or unacceptable toxicity. CT scan and PET scan were planned at baseline and q4weeks thereafter. Independent review of all CT scans was made and ≥ 5 RECIST CR+PR were required to conclude for activity according to Simon’s 2-stage design. 50 mL of EDTA blood samples were collected at baseline and q4wks in all pts to analyze plasma VEGF, sVEGFR-1,-2 and -3, c-Kit, IL-6, 8 and 12 by multiplex ELISA plates. Results: 41 pts were enrolled from 02/2010 to 07/2011. 15 pts (37%) had UC of the upper urinary tract. 20/41 pts were treated in 3 rd line or beyond. 19 pts (46%) were CDDP-refractory and 22 (54%) had hepatic metastases. 27 (66%) had ECOG PS 1-2. 7 pts (17%) had a confirmed PR, 24 had a SD (76% clinical benefit). 20 pts (49%) had a confirmed necrotic evolution of metastases and/or a decreased SUV at PET consistent with PR. Median PFS and OS (95% CL) were 2.6 (1.7-3.7) and 4.7 mos (4.2-7.3), respectively but 7 pts (17%) had long-term cure for &gt;10mos (4/7 beyond 2 nd line). G3 hypertension occurred in 2 pts, diarrhoea in 5, anemia and hand-foot syndrome in 3 pts each. Significant increase from T0 (baseline) to T1 (+4wks) level was observed for VEGF (p&lt;0.0001), IL6 (p&lt;0.0129) and IL8 (p&lt;0.0013) and decrease for VEGFR2 and c-Kit (p&lt;0.0001 each). Rising IL8 T1 levels significantly associated with RECIST progression at covariance analysis (p=0.0104). Elevated IL8 T1 levels (IQ range, HR=2.11), liver mets (HR=2.33), PS (HR=3.73) and upper tract UC (HR=0.33) were significant variables for OS at multivariate Cox analysis. Conclusions: This is the 1 st trial ever presented to meet the primary endpoint with a targeted drug in UC. A role for antiangiogenesis in UC has been set. Increasing levels of IL8 were associated with PD and worse outcome and may be included in a new prognostic model. Future investigation should aim at targeting IL8 to improve efficacy results by prolonging responses.
Ros1 Rearrangements and Copy Number Alterations in Nsclc Patients: High Frequency of Ros1 Deletions
Authors: S. Clavé, J. Gimeno, S. De Muga, L. Pijuan, J. Vidal, M. Lorenzo, S. Menendez, A. Taus, A.M. Muñoz-Mármol, E. Carcereny, N. Reguart, J.L. Mate, S. Serrano, J. Albanell, B. Espinet, E. Arriola, M. Salido
Journal: Annals of Oncology (2014)
Gliomatosis Cerebri: A pediatric case series and review of the literature
Authors: G. T. Armstrong, P. C. Phillips, L. B. Rorke-Adams, A. Judkins, A. R. Localio, M. J. Fisher
Journal: Journal of Clinical Oncology (2006)

9056 Background: Gliomatosis Cerebri (GC) is a rare and universally fatal glial neoplasm of the central nervous system. Although over 160 cases have been reported in the medical literature, the largest pediatric case series published to date includes only three patients. We describe the largest cohort to date of children with GC and explore relationships between potential prognostic factors, treatment, and survival. Methods: Imaging, pathologic, and outcome information were reviewed for this case series of thirteen patients diagnosed with GC and treated at the Children’s Hospital of Philadelphia (CHOP) between 1982 and 2005. All patients had GC confirmed by biopsy. Twelve patients were treated with cranial irradiation; eight of these received adjuvant chemotherapy as well. A single patient under one year of age was treated with chemotherapy alone. A review of the literature identified 51 reported cases of GC in the pediatric population. Results: The progression free survival (PFS) in the CHOP cohort was 13% (range: 1.5–22.5 months) and the overall survival rate (OS) was 64% (range: 6.5–27 months) at 2 years. Time to progression was significantly prolonged for those with no evidence of tumor enhancement on initial imaging (p = .03). OS was significantly shorter for patients who presented in the first decade of life (p = .04). When survival data from patients reported in the literature are combined with the CHOP cohort, treatment significantly prolonged OS (p = .003). Conclusions: Outcome in pediatric patients with GC is extremely poor, however treatment prolongs OS. Age less that 10 years and enhancement on MRI at diagnosis may be risk factors for shorter survival. No significant financial relationships to disclose.
Therapeutic starvation and autophagy in prostate cancer: A new paradigm
Authors: R. S. DiPaola, D. Dvorzhinski, M. May, R. Morton, D. Foran, K. Bray, C. Karp, E. White
Journal: Journal of Clinical Oncology (2007)

10530 The metabolic fragility of cancer cells is magnified with the preferential utilization of glycolysis that metabolizes glucose inefficiently rather than oxidative phosphorylation (the “Warburg effect”) and from impaired mechanisms of survival. In fact, one pathway by which cells survive metabolic stress is thought to be autophagy, a catabolic process of organelle digestion, which creates ATP during periods on nutrient limitation. Remarkably, autophagy is often impaired in human prostate cancers, due to either activation of the PI-3 kinase/Akt/mTOR pathway, which normally inhibits autophagy, or through allelic loss of the essential autophagy gene beclin1. This suggests that prostate cancers may be susceptible to metabolic stress that can be exploited therapeutically. Using immortalized mouse epithelial prostate cells, as well as PC-3 and LNCaP cell lines, we demonstrated the cytotoxic effect of 2-deoxyglucose (2DG), as an inhibitor of glycolysis. We found that 2DG induced membrane translocation in cells characteristic of autophagy using a transfected pEGFP-LC3 autophagy marker construct. We then demonstrated that induction of autophagy was dependent on Beclin1 expression in these cell models using Beclin1 siRNA. Based on these data, we initiated a phase I/II clinical trial with 2DG in patients with advanced malignancies and prostate cancer, which is now ongoing. In an effort to develop markers of autophagy for assessment in a clinical trial, we stained a human prostate TMA (&gt;35 patient cores) for Beclin1 by IHC. Beclin1 staining was increased in tumor tissue compared to normal tissue. Staining was imaged and digitized using a 40x volume scan on a high- throughput MedMicro whole slide scanner. The imaged specimens were stored in multi-tiled TIFF format on a redundant array of independent devices (RAID); staining will be analyzed using a color decomposition algorithm and compared to tumor characteristics as we have previously done (Foran DJ et al., IEEE Trans Inf Technol Biomed, 8:89–96, 2004). These data further support the rationale to inhibit metabolism in cancer and the potential importance of autophagy with metabolic approaches to therapy. Further imaging assessment and analysis of markers of autophagy such as Beclin1 are ongoing. No significant financial relationships to disclose.
A PETHEMA study of high-dose therapy/stem cell support (HDT), including tandem transplant, in primary refractory multiple myeloma (MM): Identification of two populations with different outcomes
Authors: J. Blade, L. Rosiñol, R. García-Sanz, J. Lahuerta, M. Hernández, A. Sureda, J. de la Rubia, J. Besalduch, J. García- Laraña, J. San Miguel
Journal: Journal of Clinical Oncology (2007)

8021 Background: It has been claimed that patients with primary refractory myeloma benefit from early HDT. However, the reported series have 2 shortcomings: 1) patients with “unresponsive-progressive disease” vs those “non-responding-non progressing” were not analyzed separately and 2) some included patients had MR or even PR according to the EBMT criteria. Aim: Response and survival after early HDT in the two populations of truly primary refractory MM Methods: From Oct 1999 to Dec 2004, 829 patients with MM received 6 cycles of VBMCP/VBAD and at least one transplant. 79 of the 829 patients were refractory to VBMCP/VBAD. These resistant patients were scheduled to receive a tandem transplant, the first with Bu-12/MEL-140 or MEL-200 and the second “autologous” with CVB or “allo- RIC” (if donor available) with Fluda/MEL-140. Response and progression were defined by the EBMT criteria. Results: 32 of the 79 primary refractory patients had progressive disease under the initial chemotherapy while 47 were “unresponsive, non-progressive”. The prognostic features, including cytogenetics, were similar in both groups. 70% of the patients responded to the first HDT (CR/nCR 8%, PR 48%, MR 13%). 37 patients were given a second transplant (26 “auto”, 11 “allo”). 41% who received a second “auto” up-graded their response (CR 9%, PR 14%, MR 18%) while 42% who underwent “allo-RIC” increased their response (CR 28%, PR 14%). Median survival of the whole series was 3 years. Patients progressing while on therapy had a shorter survival than the “no-change” group (median 2 yrs vs not reached, p=0.00002). Finally, the 47 “non-responsive, non-progressors” patients had similar survival than the 718 with chemosensitive disease intensified with HDT. Conclusions: 1) HDT in patients with primary refractory MM results in a low CR rate, 2) patients progressing while on initial therapy have a short survival despite the intensive approach and 3) patients with “non-responding, non-progressive” disease have similar survival than chemosensitive patients. Whether this good outcome is due to the impact of HDT or to the natural history of a more indolent disease remains to be determined. No significant financial relationships to disclose.
Isolation of Polyoma Virus-Induced Surface Antigens in Hamster Cells: Potassium Chloride Solubilization and Differential Precipitation 2
Authors: Yves Barra, Anne-Marie Astier, Georges Meyer
Journal: JNCI Journal of the National Cancer Institute (1977)

Surface antigens were extracted in soluble and active form with 3 M KCL from polyoma virus-transformed and embryonic hamster cells. These were tumor-specific transplantation antigens (TSTA), shown by tumor rejection, and a surface (S) antigen, demonstrated by the inhibition of surface fluorescence on living polyoma virus-transformed cells. The extracts were fractionated by salting out with ammonium sulfate. In tumor cell extracts, all TSTA activity and a part of S antigen activity were found in the fraction precipitated with 60% saturation in (NH/)2SO4. Another part of S antigen activity was found in the fraction precipitating at 80% saturation in tumor cell extracts. The precipitate at 60% saturation of embryonic cell extracts also had a part of S antigen activity. Receptor site activity for concanavalin A was also retained after solubilization and was confined to the 40% saturation (NH4)2SO4 precipitate in the case of tumor and embryonic cell extracts.
DNA methylation marker and prediction of outcome in node-positive, estrogen-receptor positive breast cancer patients receiving adjuvant anthracyclin-based chemotherapy
Authors: J. W. Martens, O. Hartmann, F. Spyratos, N. Harbeck, M. Schmitt, F. Lerebours, S. Eppenberger-Castori, V. Vuaroqueaux, J. Foekens, R. Lesche
Journal: Journal of Clinical Oncology (2008)

11046 Background: We have shown that DNA methylation of the PITX2 gene predicts risk of distant recurrence in steroid hormone receptor-positive, node-negative breast cancer. Here, we present results from a multi-center study investigating whether PITX2 and other candidate DNA methylation markers predict outcome in node-positive, estrogen receptor (ER)-positive, HER2-negative breast cancer patients who received adjuvant anthracyclin-based chemotherapy. Methods: Using a microarray platform, we analyzed DNA methylation in regulatory regions of PITX2 and 60 additional candidate genes in 241 breast cancer specimens. Using Cox regression analysis we assessed the predictive power of the individual marker/marker panel candidates. Clinical endpoints were time to distant metastasis, disease-free survival, and overall survival. A nested bootstrap/cross-validation strategy was applied to identify and validate marker panels. Median follow-up was 82 months. Results: DNA methylation of PITX2 and 14 other genes was significantly correlated with clinical outcome. In multivariate models, each methylation marker added significant information to established clinical factors. A 4-marker panel including PITX2, BMP4, FGF4, and C20orf55 was identified that resulted in further improvement of outcome prediction compared to PITX2 alone. Conclusions: This study provides further evidence for the PITX2 biomarker, which has now been successfully confirmed to predict outcome among different breast cancer patient populations. We further identify new DNA methylation biomarkers, 3 of which can be combined into a panel with PITX2 to increase the outcome prediction performance in our anthracyclin-treated primary breast cancer population. Our results demonstrate that a well- defined panel of DNA methylation markers enables outcome prediction in lymph node-positive, HER2-negative breast cancer patients treated with anthracyclin-based chemotherapy. Considering the long-term toxicities of anthracyclines and new effective non-anthracycline combinations, patients with poor outcome may be candidates for non-anthracycline regimens. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Epigenomics Epigenomics
Enzymes of Purine Metabolism in Human and Rat Renal Cortex and Renal Cell Carcinoma<xref ref-type="fn" rid="FN2">2</xref>
Authors: R C Jackson, F J Goulding, G Weber
Journal: JNCI Journal of the National Cancer Institute (1979)

Activities of seven enzymes of purine metabolism were compared in human and rat renal cortex and in human and rat renal cell carcinoma. The enzymes adenosine deaminase, adenosine kinase, AMP deaminase, adenylosuccinate lyase, adenylosuccinate synthetase, GMP kinase, and IMP dehydrogenase were selected because they showed characteristic activity changes in hepatomas relative to normal liver. The activities of thase enzymes in human renal cortex were in the same range as, or lower than, their activities in rat kidney; the largest relative difference was in adenosine deaminase activity, which in human renal cortex was 36% of that in the rat. In renal cell carcinoma of human or rat, activities of AMP deaminase, adenylosuccinate lyase, adenylosuccinate synthetase, and IMP dehydrogenase were significantly higher (149–324%) than in the respective renal cortexes. GMP kinase activity in the tumors was in the same range as that in kidney cortex, and adenosine kinase activity was markedly decreased in the tumors relative to kidney in both species. Adenosine deaminase activity in rat kidney tumors was lower (20–22%) than in normal rat kidney, but activity in the human tumors was in the normal range. With the exception of adenosine deaminase, the behavior of these enzymes in kidney tumors relative to normal kidney resembled the changes seen in hepatomas as compared with normal liver. The close biochemical resemblances of the transplantable rat kidney tumors to the human renal cell carcinomas suggested that the experimental tumors used in this study may provide a suitable model system for chemotherapy of renal cell carcinoma.
Pulmonary manifestations in rheumatoid arthritis: A hospital based descriptive study
Authors: Pratap Upadhya, Vinod S. Kumar, Manoj Kumar Panigrahi, Negi Veer Singh
Journal: European Respiratory Journal (2014)

BACKGROUND: Pulmonary involvement in RA is a major source of morbidity and mortality. Lack of Indian studies in this prompted the present study.

AIMS and Objectives-

1-To study the pulmonary manifestations of rheumatoid arthritis by clinical, radiological and physiological methods.

2-To identify the associations between lung manifestations and duration of the disease.

MATERIALS AND METHODS: This study was conducted for 2 years in department of Pulmonary Medicine. One ninety cases of Rheumatoid Arthritis fulfilling ACR/EULAR 2010 criteria were screened for respiratory symptoms and evaluated.

RESULTS: 

1) Female patients with pulmonary symptoms outnumbered male patients[female:male=5.3:1]-. 2) Thirty eight(15%) out of 190 had significant pulmonary manifestations. 3) Usage of the DMARD was present in 78.9% of patients 4) Predominant respiratory symptom was dyspnea [73.6%] followed by hemoptysis [13.1%] and cough [10.52%]. 5) The predominant chest x-ray finding was reticulonodular in 16 [42.1%]. 6) Eight patients had normal HRCT [21.1%] and predominant lung abnormality in HRCT chest was bronchiectasis [42.1%] followed by interstitial lung disease [21%]. 7) Pulmonary hypertension was seen in 7 patients. 8) Twenty one [71%] patients had small airway obstruction. 9) DLCo was normal in 12 patients and reduced in 24 patients.

CONCLUSIONS: 

1) In RA patients having respiratory symptoms and with normal HRCT chest, PFT showed small airway dysfunction and hyperactive airway disease. Thus highlighting the importance of airway disease in RA patients.

2) Reduced DLCo can the earliest indicator of lung manifestation. DLCo reduction correlates with lung manifestation and not with Rheumatoid Arthritis disease duration.