tbuckley/cabot-search huggingface dataset:
A phase I study of pemetrexed (P) plus gemcitabine (G) in relapsed ovarian cancer (OC): Dosing results and evidence of activity
Authors: M. L. Hensley, F. Derosa, S. R. Gerst, P. Sabbatini, J. Dupont, J. Konner, T. Goss, M. Orlando, Y. Wang, C. Aghajanian
Journal: Journal of Clinical Oncology (2006)

5083 Background: High expression of folate receptors on ovarian cancer cells may provide excellent targets for P. Preclinical data support synergism with G. Optimal doses of q 14 day P+G with vitamin support in pre-treated OC pts are not known. We sought to determine the maximally tolerated doses (MTD) and to assess for toxicity and activity in relapsed OC. Methods: Pts with relapsed OC, no prior P or G, KPS ≥ 70, and adequate organ function were eligible. Pts were enrolled in cohorts of 3, expanding to 6 if dose-limiting toxicity (DLT) was observed during the first 4 cycles. Pts received P at 300 (cohort 1) or 400 (cohort 2) or 500 (cohort 3) or 600 (cohort 4) mg/m 2 followed by G 1500 mg/m 2 q 14 d without GCSF. B12 and folic acid were given 1 week prior and continued throughout. DLT was defined as grade (gr) 4 neutropenia (ANC) lasting &gt;7d or neutropenic fever (NF); gr 4 thrombocytopenia or gr 3 with bleeding; ≥gr 3 nonhematologic toxicity, except ALT, AST, alopecia, fatigue; treatment delay ≥1 week due to any unresolved toxicity. Response assessed by RECIST. Results: 16 pts (median age 55, range 43–75; median number prior cytotoxic regimens 2, range 1–4) have enrolled in 4 cohorts. 15 are evaluable for response (1 treated after resection of recurrence); 13 of these15 had a platinum-free interval &lt;6 months. 1 pt in cohort 1 had global deterioration during cycle 1 and was replaced, with best response counted as progressive disease (PD). 1 pt in cohort 3 had dose delay ≥1 week, meeting DLT criteria. Cohort 3 was expanded to 6 pts with no further DLT. 3 pts enrolled in cohort 4 with no DLTs observed. Toxicities per cycle (n = 108): gr 3 ANC 31%; gr 4 ANC 27%; gr 3 dehydration 0.9%; gr 3 platelets 0.9%; 0 pts had NF. Median # cycles/pt was 6, range 1–16, median cycle length 14 d. Objective response was observed in 27% (4/15 pts: 4 PR; 7 SD; 4 PD). All 4 responses were among pts with platinum resistant disease. &gt;50% decrease in CA125 for more than two measurements was observed in 9/15 (60%) pts with evaluable CA125s. Median time to progression is 15 wks (95% confidence interval 10–32 wks). Conclusions: MTD is not yet reached. P 500 mg/m 2 + G 1500 mg/m 2 with vitamin supplementation is safe in pts with previously treated OC. 27% of patients with platinum-resistant disease had objective responses. [Table: see text]
Ermetic-2 Project : Impact of Systematic Egfr and Kras Mutation Evaluation By Alternative Testing Methods on Progression-Free (Pfs) and Overall Survival (Os) in Patients with Advanced Non–Small-Cell Lung Cancer (Nsclc) Treated By Erlotinib (E) in the Ifct Ermetic Cohort
Authors: M. Beau-Faller, M. Texier, H. Blons, N. Richard, F. Escande, I. Bièche, S. Lizard, F. De Fraipont, F. Morin, G. Zalcman, J. Pignon, J. Cadranel
Journal: Annals of Oncology (2014)
Early nephropathy predicts vision-threatening retinal disease in patients with type I diabetes mellitus.
Authors: R E Gilbert, C Tsalamandris, T J Allen, D Colville, G Jerums
Journal: Journal of the American Society of Nephrology (1998)

In type I (insulin-dependent) diabetes mellitus, nephropathy may be identified in its early stages by the development of persistent microalbuminuria. This longitudinal study sought to examine the development of vision-threatening retinal disease (VTRD) (proliferative retinopathy and clinically significant macular edema) in such patients with early and evolving diabetic kidney disease. Eighty patients with type I diabetes and at least 8 yr of longitudinal data were identified. Glycated hemoglobin and albumin excretion rate (AER) were measured every 3 mo. Ophthalmologic examination was performed at least yearly. Thirteen patients were identified as having evolving nephropathy by a progressive increase in AER and the presence of microalbuminuria during the study period. Sixty-seven patients remained persistently normoalbuminuric. VTRD developed in eight of 13 (62%) patients with evolving nephropathy compared with five of 69 (7%) patients who were persistently normoalbuminuric (P < 0.001) in the absence of any difference in long-term glycemic control or duration of diabetes between the two groups. Clinically significant macular edema (P < 0.05) and proliferative retinopathy (P < 0.01) were both more common in patients with evolving nephropathy. In such patients, AER was 150 x/divided by 1.7 micrograms/min at the time of laser photocoagulation for VTRD. These data suggest that patients with type I diabetes and evolving nephropathy may be at higher risk of developing VTRD than patients who remain persistently normoalbuminuric despite similar long-term glycemic control and duration of diabetes.
Mortality in a group of formerly incarcerated juvenile delinquents
Authors: C A Yeager, D O Lewis
Journal: American Journal of Psychiatry (1990)

A 7-year follow-up study of formerly incarcerated delinquents revealed an extremely high mortality rate. Of 118 male and female subjects, seven had died before their 25th birthdays, making the mortality rate of the sample approximately 58 times the national average for individuals in their age group. All died violent deaths, making the violent death rate of the sample approximately 76 times the national average for that age group. Differences in mortality rates according to the race and sex of the subjects are reported, and possible clinical predictors of early death are explored.
Gastroesophagial reflux disease and asthma in pregnant women
Authors: Katayoon Bidad, Nasrin Zendehdel, Hassan Heidarnazhad, Zahra Pourpak, Mostafa Moin
Journal: European Respiratory Journal (2011)

Introduction:  Asthma, as a public health problem world-wide, seems to be significantly associated with GERD. GERD and its symptoms are also more prevalent in pregnant women, worsening by the increase in gestational age. This study aimed to evaluate GERD and its relation to asthma in pregnant women.   Methods:  One-hundred and seventy three pregnant women (mean age, 28.8±5.3 years and mean gestational age, 24.8±9.2 weeks) were included. The diagnosis of asthma was made on the basis of the Guidelines of the National Asthma Education and Prevention Program (NAEPP). As challenge tests are not recommended in pregnancy, a group of patients were classified as probable-asthmatics. They were the cases in whom symptoms and signs were suggestive of asthma but the spirometry was normal.   Results:  Asthma was diagnosed in 37% of the included women and 26.6% were probable to have asthma, while 36.4% were non-asthmatics. GERD was present in 80.9% of the pregnant women. GERD was not significantly higher in asthmatic or probable asthmatic women compared to non-asthmatic ones, but in pregnant women who had asthma, GERD was significantly more severe compared to women who did not have asthma (p=0.02).   Conclusion:  In this study, we observed a high prevalence of GERD in pregnant women. Although GERD was not higher in asthmatic or probable asthmatic pregnant women, it tended to be more severe in asthmatic cases. This points to the importance of early diagnosis and treatment of GERD in asthmatic pregnant women.
STK11/LKB1 Deficiency Promotes Neutrophil Recruitment and Proinflammatory Cytokine Production to Suppress T-cell Activity in the Lung Tumor Microenvironment
Authors: Shohei Koyama, Esra A. Akbay, Yvonne Y. Li, Amir R. Aref, Ferdinandos Skoulidis, Grit S. Herter-Sprie, Kevin A. Buczkowski, Yan Liu, Mark M. Awad, Warren L. Denning, Lixia Diao, Jing Wang, Edwin R. Parra-Cuentas, Ignacio I. Wistuba, Margaret Soucheray, Tran Thai, Hajime Asahina, Shunsuke Kitajima, Abigail Altabef, Jillian D. Cavanaugh, Kevin Rhee, Peng Gao, Haikuo Zhang, Peter E. Fecci, Takeshi Shimamura, Matthew D. Hellmann, John V. Heymach, F. Stephen Hodi, Gordon J. Freeman, David A. Barbie, Glenn Dranoff, Peter S. Hammerman, Kwok-Kin Wong
Journal: Cancer Research (2016)

Abstract STK11/LKB1 is among the most commonly inactivated tumor suppressors in non–small cell lung cancer (NSCLC), especially in tumors harboring KRAS mutations. Many oncogenes promote immune escape, undermining the effectiveness of immunotherapies, but it is unclear whether the inactivation of tumor suppressor genes, such as STK11/LKB1, exerts similar effects. In this study, we investigated the consequences of STK11/LKB1 loss on the immune microenvironment in a mouse model of KRAS-driven NSCLC. Genetic ablation of STK11/LKB1 resulted in accumulation of neutrophils with T-cell–suppressive effects, along with a corresponding increase in the expression of T-cell exhaustion markers and tumor-promoting cytokines. The number of tumor-infiltrating lymphocytes was also reduced in LKB1-deficient mouse and human tumors. Furthermore, STK11/LKB1–inactivating mutations were associated with reduced expression of PD-1 ligand PD-L1 in mouse and patient tumors as well as in tumor-derived cell lines. Consistent with these results, PD-1–targeting antibodies were ineffective against Lkb1-deficient tumors. In contrast, treating Lkb1-deficient mice with an IL6-neutralizing antibody or a neutrophil-depleting antibody yielded therapeutic benefits associated with reduced neutrophil accumulation and proinflammatory cytokine expression. Our findings illustrate how tumor suppressor mutations can modulate the immune milieu of the tumor microenvironment, and they offer specific implications for addressing STK11/LKB1–mutated tumors with PD-1–targeting antibody therapies. Cancer Res; 76(5); 999–1008. ©2016 AACR.
Post-thrombotic syndrome after catheter-directed thrombolysis for deep vein thrombosis (CaVenT): 5-year follow-up results of an open-label, randomised controlled trial
Authors: Ylva Haig, Tone Enden, Ole Grøtta, Nils-Einar Kløw, Carl-Erik Slagsvold, Waleed Ghanima, Leiv Sandvik, Geir Hafsahl, Pål Andre Holme, Lars Olaf Holmen, Anne Mette Njaaastad, Gunnar Sandbæk, Per Morten Sandset
Journal: The Lancet Haematology (2016)
Potent tumor killing and inhibition of tumor growth by CEA/CD3-bispecific single chain antibodies that are resistant to inhibition by soluble CEA
Authors: Ralf Lutterbuese, Tobias Raum, Roman Kischel, Petra Lutterbuese, Bernd Schlereth, Patrick Baeuerle, Peter Kiener, Scott Hammond, Peter Kufer
Journal: Cancer Research (2007)

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

4106 

Introduction: 

Carcinoembryonic antigen (CEA) is a well-characterized target antigen for antibody-based cancer therapy. Expression of CEA on normal adult tissue is restricted to the luminal surface of intestinal epithelia, where it is inaccessible to systemically administered antibodies. In contrast, CEA is highly expressed in a non-polarized fashion on various adenocarcinomas, including colorectal, pancreatic and gastric cancer. As a novel therapeutic approach for treatment of CEA-expressing tumors we constructed bispecific single-chain antibodies (scFv) of the BiTE format by combining human anti-CEA scFvs with a single deimmunized anti-human CD3 scFv, respectively.

Experimental Procedures: 

Dose dependency of redirected lysis of CEA-expressing human tumor cell lines was investigated by a 51Cr-release assay. Unstimulated human PBMC, or stimulated CD8+ T cells from healthy donors were used as effector cells. Human CEA/mouse CD3-specific BiTE molecules were tested for inhibition of lung tumor growth in immunocompetent Balb/C mice.

Results: 

Various CEA-specific BiTE molecules were constructed from CEA-specific scFvs and efficiently redirected the cytotoxic activity of human T cells to kill CEA-positive tumor cell lines without the need for T cell costimulation. BiTE molecules selected for further development showed half-maximal tumor cell lysis at concentrations as low as of 5 pg/mL with activated human CD8+ T cells, and 0.5 ng/mL with unstimulated human PBMC as effector cells. The cytotoxic activity of certain CEA-specific BiTE molecules were resistant to concentrations of soluble CEA of up to 1 µg/mL, a level higher than found in the serum of most cancer patients. For in vivo proof of concept studies, selected anti-human CEA scFvs were combined with a scFv specific for murine CD3 to generate BiTE molecules capable of recruiting murine T cells for redirected tumor lysis in immunocompetent mice. Untreated mice developed on average 100 tumor colonies in the lung after intravenous inoculation with a syngeneic murine colorectal cancer cell line transfected with human CEA. In contrast, treatment of tumor bearing mice with 1 µg murine-specific CEA-BiTE once daily for 5 days almost completely inhibited outgrowth of lung tumors.

Conclusions: 

Novel CEA-specific BiTE molecules with potent in vitro and in vivo anti-tumor activity were generated; a subset were resistant to inhibition by soluble CEA. In light of its potent efficacy, CEA-specific BiTE molecules may prove a useful and novel approach for the treatment of CEA-expressing human adenocarcinomas.
Survival of Allogeneic Stem Cell Transplantation Vs Conventional Therapies per DIPSS Stratification in Patients with Primary Myelofibrosis Younger Than 65 Years: A Retrospective Analysis on 673 Patients
Authors: Nicolaus Kröger, Toni Giorgino, Bart L Scott, Marcus Ditschkowski, Haefaa Alchalby, Francisco Cervantes, Alessandro M. Vannucchi, Mario Cazzola, Enrica Morra, Tatjana Zabelina, Margherita Maffioli, Arturo Pereira, Dietrich Beelen, H. Joachim Deeg, Francesco Passamonti
Journal: Blood (2014)
Dose intensive chemotherapy (Cx) in advanced thymoma: Initial report of Japan Clinical Oncology Group trials (JCOG 9605 and 9606)
Authors: H. Kunitoh, T. Tamura, H. Fukuda, K. Nakagawa, K. Takeda, Y. Nishiwaki, N. Katagami, A. Yokoyama, K. Noda, N. Saijo
Journal: Journal of Clinical Oncology (2006)

7080 Background: Thymoma is considered to be sensitive to Cx. Dose intensive Cx might well be suitable for such tumors, especially in combination with local therapy. Objectives of the trials were to evaluate the safety and efficacy of the dose intensive CODE (cisplatin[C]- vincristine[O]- doxorubicin[D]- etoposide[E]) Cx in thymoma. The primary endpoint was progression-free survival time (PFS). Methods: Patients (pts) with 15–70 years of age with histologically documented Cx-naïve thymoma with stage IVa/IVb disease (JCOG 9605) or unresectable stage III disease (JCOG 9606) were eligible. Tumors of other histology, such as thymic carcinoma, carcinoid or lymphoma were excluded; pts were to have ample organ function and ECOG PS of 0–2. Myasthenia was allowed. Signed consent form was obtained. Pts received CODE Cx of 9 weeks (w): C 25 mg/m 2 Cx day 1 on each w1–9; O 1mg/m 2 d1 on w1,2,4,6,8; D 40 mg/m 2 d1 and E 80 mg/m 2 d1,2,3 on w 1,3,5,7,9. Cx courses were supported by GCSF. Steroids were used only for antiemesis. Those with stage III disease (JCOG 9606) went on to surgery, if judged to be resectable, and post-operative radiotherapy (RT) of 48Gy; those with unresectable disease received 60Gy RT. Results: From Jul./97 to Apr./05, 53 pts were entered to the studies. Five were found ineligible because of different histology. Pt characteristics and response to the Cx were summarized in the table . Toxicity of the Cx was mainly hematologic and generally well tolerated, with no toxic death; 70% of the pts completed planned 9 weeks. Thirteen pts in JCOG 9606 (stage III) received thoracotomy; tumor was resected in 11 pts, completely in 9 (39% of enrolled pts). Pathologic CR was observed in 3. The median PFS was 9.5m for stage IV and 4.5 y for stage III diseases. Overall survival at 2 &amp; 5 yrs were 82% &amp; 57% for stage IV and 96% &amp; 77% for stage III pts. Conclusions: Short-course, dose intensive Cx was active against thymoma. Although it does not seem to bring long PFS in stage IV pts, it could improve resectability in limited disease. [Table: see text] No significant financial relationships to disclose.
Treatment of metastatic renal cell carcinoma by continuous intravenous infusion of recombinant interleukin-2: a single-center phase II study.
Authors: P F Geertsen, G G Hermann, H von der Maase, K Steven
Journal: Journal of Clinical Oncology (1992)

PURPOSE A single-center phase II study was performed to evaluate the efficacy of recombinant interleukin-2 (rIL-2) administered by continuous infusion to patients with metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS Thirty-one patients with RCC were entered onto the study. rIL-2 (Proleukin; Eurocetus Corp, Amsterdam, The Netherlands) was administered intravenously in a dose of 18 x 10(6) IU/m2 per 24 hours. A maximum of two induction cycles and four maintenance cycles were given. Each induction cycle consisted of two rIL-2 infusion periods of 120 hours and 108 hours duration, respectively; these were separated by a 6-day rest period. Each maintenance cycle consisted of a 120 hours rIL-2 infusion period. RESULTS Six of 30 assessable patients (20%) responded; two (7%) with a complete response (CR) and four (13%) with a partial response (PR). The response duration for patients with CR was 209 and 715+ days, and for those with PR 161, 197, 245, and 353 days. Seven patients had stable disease (SD) with a median duration of 261 days (range, 127 to 381 days). The overall median survival was 261 days (range, 13 to 905+ days). The most frequent toxicities requiring dose reductions of rIL-2 were: hypotension in 87% of patients, dyspnea in 32%, CNS toxicity in 55%, and an increase in serum creatinine levels in 48%. Septicemia occurred in 16% of patients. Toxicities usually reversed on interruption of rIL-2 infusion. One patient (3%) died as a result of the treatment from initial CNS toxicity followed by multiorgan failure. CONCLUSIONS The study confirmed the antitumor efficacy of rIL-2 administered by continuous infusion in patients with metastatic RCC. The response rate was similar to that obtained by high-dose bolus injections of rIL-2. Toxicity was substantial but manageable in a specialized oncology ward without routine use of an intensive care unit.
Autologous transplant of hematopoietic cells: Results from cryopreservation in Sanatorio Allende from Cordoba
Authors: M. L. Salvano, G. Molina Barrios, C. Bonini Colmano, S. Molnar, M. Arévalo, C. Dubersarsky, D. Minoldo, M. L. Rizzi, M. Lavarda, G. D. Jarchum
Journal: Journal of Clinical Oncology (2007)

17530 Background: Preservation of hematopoietic cells (HC) is usually achieved by storing cells in liquid nitrogen at - 196 0 C (Cryopreservation) (CP). We aim to: observe how many leukapheresis (LK) were necessary in order to obtain the minimal number (n°) of HC (CD34+/kg) for a proper engraftment (EG); correlate the n° of cryopreservated and infused cells with the time of EG; determine if the time of CP at -80 0 C influences the time of EG; determine if the pre-transplant (PT) condition (partial or complete remission) plays a role in the time of EG and/or the time of hospitalization of the patients (pts). Methods: This was a retrospective study. We included all pts that received autologous transplant which HC after CP in our institution between September 2004 and August 2006. Qualitative results were analyzed by Fischer exact test and relation between qualitative and quantitative results by Mann-Whitney/Wilcoxon two- sample test (Kruskal-Wallis test for two groups). Results: 27 pts were included (N=27); the average age was 48.3± 16.6 years with a range of 64 (4–68) years. Diagnosis included: Multiple Myeloma 40%, NHL 22%, Hodgkin disease 15%, AML 15%, Amyloidosis 4%, and Ependymoma 4%. In 66.7% of the pts only one round of LK was needed for recollection. The CP time at -80 0 C had a range of 113 (8–122) days. The median time for EG was 11 days for neutrophils (nt) and 17 days for platelets (pl). There was not significant correlation between PT condition and: n° of nt before or after day 11 (p=0.515); n° of pl before or after day 17 (p=0.972); hospitalization time (p=0.55); time for EG of nt (p-0.553) and pl (p=0.936). There was a significant difference between receiving =5x10 6 CD34+/Kg and pl EG time before day 17 (p=0.01) but not for nt EG time (p=3.83). CP time had no significant difference in relation to the pl EG before or after day 17 (p=0.08) or nt EG before or after day 11 (p=0.49). Conclusions: The majority of pts had a proper CD34+/Kg count with one LK round. Doses =5x10 6 CD34+/Kg were associated with less time for pl EG. The storage of HC at -80 0 C showed to be safe for periods between one week and 4 months. The time of storage at -80 0 C did not seem to affect the time of EG but showed a trend towards slowing pl recovery. The PT condition did not correlate with the time for EG or the hospitalization time. No significant financial relationships to disclose.
The aerodynamic particle size of mometasone furoate 100 μg and 200 μg dry powder formulations
Authors: Robert Berger, Steven Li, Heribert Staudinger
Journal: European Respiratory Journal (2011)

Background:  Regional lung deposition of inhaled particles depends on aerodynamic particle size, as well as inspiratory flow rate and other factors. Inhaled particles of aerodynamic sizes of approximately 2 μm have been found to deposit most efficiently in the alveolar region across a broad range of inspiratory flow rates. In vivo studies of mometasone furoate (MF) delivered by the Twisthaler® showed mean peak inspiratory flow rates at satisfactory levels in adult/adolescent patients aged ≥12 years (69 L/min), children aged 9–12 years (>60 L/min), and children aged 5–8 years (>50 L/min).   Objective:  We report aerodynamic particle size findings from an in vitro study analyzing the mass median aerodynamic diameter (MMAD) of MF.   Methods:  Twelve inhalers each of the 100 and 200 μg strengths were tested in vitro at the beginning and end of unit lives at a 60 L/min flow rate. Aerosolized MF was collected by cascade impaction for 2 inhalations from the 100 μg strength and 1 inhalation from the 200 μg strength, thereby providing similar particle masses.   Results:  The average MMAD of the 100 μg strength for beginning and ending inhalations (n=24) was 2.0 μm (range, 1.9–2.1 μm), while the 200 μg strength for beginning and ending inhalations (n=24) was 2.2 μm (range, 2.0–2.4 μm).   Conclusion:  Average MMAD values of MF for both strengths measured in vitro at a clinically relevant flow rate, together with in vivo particle-size efficiency deposition models, suggest that the aerodynamic particle size of MF is optimal (∼2 μm) for efficient alveolar deposition when administered via the Twisthaler®.