tbuckley/cabot-search huggingface dataset:
Sunitinib malate (SM) in alveolar soft part sarcoma (ASPS).
Authors: E. Palassini, S. Stacchiotti, T. Negri, S. Brich, A. Marrari, C. Morosi, F. Crippa, A. Gronchi, S. Pilotti, P. G. Casali
Journal: Journal of Clinical Oncology (2010)

10014 Background: ASPS is a rare soft tissue sarcoma, characterized by the t(X;17), resulting in the ASPL-TFE3 fusion protein. It carries a high metastatic potential with a typical indolent growth even in the advanced stages. ASPS is generally resistant to chemotherapy. We already reported on the activity of SM in 4 cases of ASPS. This series updates those results. Methods: Since July 2007, 10 patients (pts) with progressive metastatic ASPS (M/F 7/3; median age 24 yrs; site of primary: extremities 9, retroperitoneum 1; site of metastasis: lung 10, bone 3, liver 3, brain 2, other 4; pretreated pts: 8) have been treated with continuous SM 37.5 mg/day, on name-use basis. Responses were evaluated after 2 months from baseline, then every 3 months by CT scan and/or MRI, according to RECIST criteria. PET responses were evaluated in 5 cases. Biochemical analysis by phospho-RTK arrays complemented by downstream signaling pathway analysis was performed on 5 pts whose cryopreserved material was available. Results: At the time of the present analysis 8/10 pts are evaluable for response (2 just started), 8 pts are still on treatment. Treatment was fairly well tolerated (no G3-4 toxicity). After 3 months of treatment, 5 pts had RECIST PR, along with subjective improvement in symptoms, 1 SD, 2 PD. PR/SD were confirmed in all cases after 6 months. PET was consistent with response/progression. One patient had a secondary PD after 17 months of treatment and died one month later. Responses seemed to be long-lasting (>9 months in all cases), with one patient still responsive after 28 months. In 2 cases treatment interruptions lead to tumor progression. Response was re- established when restarting SM. Biochemical analysis showed good correlation between RTK activation profile and SM targets, and a uniform activation of AKT, ERK1-2, mTOR downstream pathways. Notably, a particularly strong activation of EGFR was evident in the case with SD. RET-mediated activation might be responsible of the 2 progressive cases. Conclusions: SM confirmed to be active in ASPS. Long- lasting dimensional responses were obtained. Interval disease progressions were recorded in case of treatment interruptions. Molecular analysis supported SM activity. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pfizer
Tyrosine Kinase 2 (Tyk2) Interacts with and Phosphorylates Siva-1, and Auguments the Apoptotic Effect Induced by Siva-1.
Authors: Haruko Kakumitsu, Kazuya Shimoda, Takashi Haro, Kotaro Shide, Takashi Kumano, Seido Oku, Kenjirou Kamezaki, Akihiko Numata, Katsuto Takenaka, Mine Harada
Journal: Blood (2006)
Review: Prucalopride, velusetrag, bisacodyl, and sodium picosulfate improve chronic idiopathic constipation
Authors: Judy Nee, Joseph D. Feuerstein
Journal: Annals of Internal Medicine (2016)

Source Citation Nelson AD, Camilleri M, Chirapongsathorn S, et al. Comparison of efficacy of pharmacological treatments for chronic idiopathic constipation: a systematic review and network meta-analysis. Gut. 2016 Jun 10. [Epub ahead of print]. 27287486
GW26-e2122 Predictive Value of HbA1c on left atrial thrombus or Left Atrial Spontaneous Echo Contrast in Non-Valvular Atrial Fibrillation Patients
Authors: Weidong Lin, Fangzhou Liu, Yumei Xue, Xianhong Fang, Xianzhang Zhan, Hongtao Liao, Shulin Wu
Journal: Journal of the American College of Cardiology (2015)
Final Report of a Phase-II Study of Rituximab Plus ABVD for Patients with Newly Diagnosed Advanced Stage Classical Hodgkin Lymphoma.: Results of Long Follow up and Comparison to Institutional Historical Data.
Authors: Amanda R Copeland, Yumei Cao, Michelle Fanale, Luis Fayad, Peter McLaughlin, Barbara Pro, Fredrick Hagemeister, Jorge Romaguera, Felipe Samaniego, Alma Rodriguez, Anas Younes
Journal: Blood (2009)
Integrative assessment of expression and prognostic value of PDL1, IDO, and kynurenine in 371 primary soft tissue sarcomas with genomic complexity.
Authors: Maud Toulmonde, Julien Adam, Alban Bessede, Dominique Ranchère-Vince, Valerie Velasco, Véronique Brouste, Jean-Yves Blay, Olivier Mir, Antoine Italiano
Journal: Journal of Clinical Oncology (2016)

11008 Background: Programmed death-ligand 1 (PD-L1), Indole 2,3 dioxygenase (IDO) or Kynurenine (K) expression has uncertain or unknown prognostic value in soft tissue sarcoma (STS)and may vary with histological subtypes intrinsic immunogenicity.We aimed to assess expression and prognostic value of these immune markers in patients (pts) with localized primary STS of specific histology with genomic complexity. Methods: We evaluated expression of PDL1, IDO and K, on immune (IC), tumoral (TC) and endothelial cells (EC) by IHC on TMA from archival formalin-fixed paraffin-embedded pathological samples of pts treated for a STS between 1980 and 2007 in 15 french centers. Results: 371 pts were included.PDL1 was ≥ 1% on tumor and/or immune cells in 72 samples (19%) and was mostly expressed by IC. IDO was positive on EC in 86 samples (23%) and ≥ 5% on TC in 152 samples (41%). K was positive in 209 samples (56%). Median follow up was 166 months [151-176]. Overall, 67 patients relapsed (18%). Age, location, histology, depth, grade and K accumulation were significantly associated with OS in univariate and multivariate analysis (Table 1). Age was the sole variable significantly associated with relapse. There was a significant consistency in joint expression of PDL1 and IDO on TC, PDL1 and K, and K and IDO on TC, in 70% (p<0.0001), 53% (p=0.0004) and 53% (p=0.05) of samples, respectively. Conclusions: In primary STS with genomic complexity, PDL1 is neither commonly expressed nor associated with survival, whereas K is. These results raise interest in deeper analysis of the K pathway and its role in STS. Variable Univariate Analyses Multivariate Analyses HR IC 95% HR p HR IC 95% HR p Age ≥ 63 years 2.6 [2-3.4] <0.0001 2.9 [2.2-3.9] <0.0001 Location Girdle 0.6 [0.5 - 0.8] 0.0006 0.6 [0.5-0.8] 0.0007 Size >90 mm 2.2 [1.5-3.3] <0.0001 3 [1.3-7.6] 0.01 Histology (LMS) Complex 0.7 [0.6-0.9] 0.03 0.7 [0.5-0.9] 0.01 DDLPS 2.2 [1.3-3.6] 0.004 1.2 [0.7-2.1] 0.5 Depth Deep or both 2 [1.2-3.2] 0.006 1.9 [1.1-3.1] 0.02 Grade Grade 3 1.7 [1.1-2.6] 0.01 1.7 [1.1-2.6] 0.02 Kynurenine positive 0.7 [0.5-0.9] 0.007 0.7 [0.5-0.9] 0.002 PDL1 ≥ 1% 1.1 [0.8-1.5] 0.62 IDO on EC positive 0.96 [0.7-1.3] 0.81 IDO on TC ≥ 5% 0.8 [0.6-1.1] 0.13
Genetic Influence on the Systems Biology of Sickle Stroke Risk Detected by Endothelial Gene Expression.
Authors: Robert P. Hebbel, Aixiang Jiang, Cheryl A. Hillery, J. Paul Scott, Steven C. Nelson, Judy Enenstein, Liming Milbauer, Vidya Bodempudi, Wei Pan, James N. Topper, Ruey-Bing Yang
Journal: Blood (2005)
A Proposal for a Serology-Based Approach to Membranous Nephropathy
Authors: An S. De Vriese, Richard J. Glassock, Karl A. Nath, Sanjeev Sethi, Fernando C. Fervenza
Journal: Journal of the American Society of Nephrology (2016)

Primary membranous nephropathy (MN) is an autoimmune disease mainly caused by autoantibodies against the recently discovered podocyte antigens: the M-type phospholipase A2 receptor 1 (PLA2R) and thrombospondin type 1 domain-containing 7A (THSD7A). Assays for quantitative assessment of anti-PLA2R antibodies are commercially available, but a semiquantitative test to detect anti-THSD7A antibodies has been only recently developed. The presence or absence of anti-PLA2R and anti-THSD7A antibodies adds important information to clinical and immunopathologic data in discriminating between primary and secondary MN. Levels of anti-PLA2R antibodies and possibly, anti-THSD7A antibodies tightly correlate with disease activity. Low baseline and decreasing anti-PLA2R antibody levels strongly predict spontaneous remission, thus favoring conservative therapy. Conversely, high baseline or increasing anti-PLA2R antibody levels associate with nephrotic syndrome and progressive loss of kidney function, thereby encouraging prompt initiation of immunosuppressive therapy. Serum anti-PLA2R antibody profiles reliably predict response to therapy, and levels at completion of therapy may forecast long-term outcome. Re-emergence of or increase in antibody titers precedes a clinical relapse. Persistence or reappearance of anti-PLA2R antibodies after kidney transplant predicts development of recurrent disease. We propose that an individualized serology-based approach to MN, used to complement and refine the traditional proteinuria-driven approach, will improve the outcome in this disease.
Mobile app user guide: Hipbone to sync personal health data
Authors: Robert D Furberg, Alexa M Ortiz
Journal: British Journal of Sports Medicine (2016)

Hipbone.

Health and Fitness.

iOS 8.0 or later. (Updated 15 March 2016: current V.0.2.1; size 19.3 MB. Documented from: https://itunes.apple.com/us/app/hipbone/id994965999?mt=8.)

Free.

The Hipbone app is offered by Open mHealth (New York, New York, USA; https://hipboneapp.com/), a non-profit start-up seeking to increase the clinical relevance and usage of self-generated health information.1 Since Apple's release of the iOS 8 operating system in September 2014, iPhone users have been able to collect and curate a variety of their own health data using the native Health application. A signification limitation, however, is that self-generated data, while appreciable in the Health app dashboard, are only stored on the device. Extraction of these data for archiving, conducting analyses or sharing with …
A pilot study of adjuvant bevacizumab and chemotherapy after neoadjuvant chemotherapy for high-risk breast cancer
Authors: E. L. Mayer, K. D. Miller, H. S. Rugo, J. M. Peppercorn, L. A. Carey, N. Ryabin, K. Josephs, E. P. Winer, H. J. Burstein
Journal: Journal of Clinical Oncology (2008)

519 Background: Patients (pts) with residual breast cancer after neoadjuvant chemotherapy are at increased risk of recurrence, and may have chemotherapy-resistant disease. We sought to explore adjuvant antiangiogenic therapy combined with two different chemotherapy regimens in this population. Methods: Eligible pts had stage II-III breast cancer with residual invasive carcinoma at surgery following anthracycline-containing neoadjuvant chemotherapy. Treatment consisted of bevacizumab (B) 15 mg/kg every three weeks (1 cycle) for one year, starting no less than 1 month after surgery or 2 weeks after radiation. Sequential cohorts also received concurrent chemotherapy, either metronomic chemotherapy (CM): cyclophosphamide 50 mg PO qd, and methotrexate 2.5 mg PO d 1–2 each week for a total of 6 months, or capecitabine (X) 2,000 mg/m2/day 14d on/7d off for 18 weeks. Concurrent endocrine and/or trastuzumab therapy was allowed. The primary endpoint was feasibility and tolerability of the combination therapy. Results: 81 pts were treated with B + CM or B + X. Median age was 48y, 59% were stage III, 62% were hormone receptor positive, and 11% were HER2+. To date, the median number of cycles completed is 10 of a planned 17, with 12 pts completing treatment and 2 pts choosing to end treatment early. At a median on-study follow-up of 7.5 months, 6 pts (7%) have had tumor recurrence. Treatment-related toxicities include fatigue (41%), headache (32%), arthralgias (31%), and hypertension (23%). Preliminary analysis suggests B + CM has a more favorable side effect profile, as B + X led to more diarrhea, hand-foot syndrome, and grade 3/4 toxicity. 9 patients came off study for toxicity, including one patient with heart failure. Definitive feasibility/safety data and preliminary correlative studies will be available by June 2008. Conclusions: Adjuvant B + chemotherapy after neoadjuvant chemotherapy appears tolerable and feasible with side effects including fatigue, headache, arthralgias, and hypertension. The addition of X appears to contribute more toxicity. As previously demonstrated in our study of B monotherapy (Mayer et al, ASCO 2007, #561), the post- preoperative chemotherapy population remains high risk and merits novel therapies. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech Genentech Genentech
The Incidence of Osteonecrosis of the Jaw (ONJ) in Patients with Multiple Myeloma Who Receive Biphosphonates Depends on the Type of Biphosphonate.
Authors: Meletios A. Dimopoulos, Efstathios Kastritis, Lia A. Moulopoulos, Ioannis Melakopoulos, Athanasios Anagnostopoulos, Dimitra Gika, George Bozas, Vassiliki Koutsoukou, Aristotelis Bamias
Journal: Blood (2005)
Metastatic adeoid cystic carcinoma of the salivary gland.
Authors: Dagmar Brancikova, Marketa Protivankova, Lenka Ostrizkova, Zdenek Mechl, Radek Pejcoch
Journal: Journal of Clinical Oncology (2015)

e17027 Background: Adeoid cystic carcinomas of the salivary gland account for approximately 10% of parotid gland tumors. Well-differentiated tumors are characterized by a slow growth rate, a low recurrence rate after complete surgical excision and rare metastatic potential. High-grade tumors are more aggressive, local reccurence rate after surgery approaches 60% and 30% develop distant metastases. We are presenting small group - 6 cases with longer survival after targeted, biological therapy Methods: 6 patients ( 4 males and 2 female) with median age: 50 years. Multiple lung and liver dissemination with all of them. Histology: adenoid cystic carcinoma, KRAS wt, ckit wt, BRAF wt with all. In one women PDGFR mutation on exon 10. No comorbidities, all tumors was clinically symptomatic. Treatment: Combination Cisplatin 50mg/m2 day 1 +Fluorouracil 100mg/m2 48 h continual and docetaxel 60mg/m2 day 1 was used on the first line , after progression in the second line patient was treated with Mitoxantron monotherapy . Third line we indicated imatinib mesylate to patients ckit wt and sunitinib undervent female patient with PDGFR mutation. Results: Therapy using docetaxel and platinum and fluorouracil was effective ( PR 4 patient , median TTP 10month ) The treatment with Mitoxantron was effective :partial regression 5 patients TTP 13 months we have documentated. The effect of the treatment with Imatinib mesylate: stabilization of the dissease 4 patient without mutation TTP longer than 5 months in all cases. Female patient with mutation was treated 8 months only,Sunitinib was ineffective.Patients PDGFR wt are alive more than 2 years with metastatic dissease Conclusions: In our group was PDGFR mutation negative prognostic factor for treatment effect and progression.Patients with ckit wt and PDGFR wt have documentated significantly better prognosis and chemotherapy response.
Effect of zoledronic acid on bone loss by letrozole
Authors: S. S. Jung, S. Cha, J. Bae, W. Park, Y. Seo, S. Oh, J. Kim, H. Jeon, B. J. Song
Journal: Journal of Clinical Oncology (2007)

11077 Background: The aromatase inhibitors cause bone loss by estrogen depletion. Zoledronic acid (ZA) can prevent bone mineral density (BMD) loss associated with the use of aromatase inhibitors. Accordingly interest has arisen in measuring surrogate markers of bone resorption to monitor the response of treatment of BMD loss in place of radiologic assessment. This study was designed to determine whether ZA would prevent bone loss that is known to occur with letrozole and identified surrogate markers of bone resorption in an animal model. Methods: In ovariectomized or sham-operated rat, we administrated ZA and letrozole to 5 different groups including: a sham operation control group (OC), a group in which an ovariectomy was performed followed by saline administration (OS), an ovariectomy with ZA treatment group (OZ), an ovariectomy with letrozole treatment group (OL) and an; ovariectomy with ZA and letrozole combined treatment group (OZL). The levels of serum osteocalcin, serum bone alkaline phosphatase (BALP), serum calcium and urine N-telopeptide (NTX) and BMD were estimated and compared at the same periods for each group. The distinct microscopic findings of proximal tibia at week sixteen were also compared. Results: Significantly intense increment of BDM in the OZ group and the OZL group and lower increment in the OL group were valued in correlation to the OS group, 31.3%, 35.0%, 10.5% and 13.0% respectively. Serum osteocalcin levels and urine calcium levels were close to each group. Serum calcium levels and BALP levels were relatively lowering in the OZ group and the OZL group than other group. Meaningfully lower levels of urine NTX were measured in the OZ group and the OZL group, 6.6% and 16.5% respectively. In the OL group levels of urine NTX were rise of 55.9%. Less cancellous bone loss and increase bone trabeculae were noted in the microscopic findings of tibia. Conclusions: The combination treatment with ZA and letrozole are effective in the inhibition of bone resorption and in the maintenance of BMD. Measurement of serum osteocalcin, urine NTX, and BMD, levels are recommended as surrogate markers for determining the response for the treatment of bone loss. No significant financial relationships to disclose.
Usefulness of Serum-Free-Light-Chains-Ratio (SFLCR) and Serum Heavy-Light-Chains-Ratio (SHLCR) in Multiple Myeloma in the Context of Three GEM/Pethema Clinical Trials
Authors: Lucia Lopez-Anglada, Cecilia Cueto-Felgueroso, Maria-Victoria Mateos, Laura Rosiñol, Albert Oriol, Ana Isabel Teruel, Ana Lopez de la Guia, Luis Palomera, Felipe de Arriba, Jose Mariano Hernandez, Miquel Granell, Francisco Javier Peñalver, Ramon Garcia-Sanz, Juan Besalduch, Yolanda Gonzalez, Rafael Martinez, Miguel Teodoro Hernandez, Norma C Gutierrez, Paloma Puerta, Joan Blade, Jesús San Miguel, Juan José Lahuerta, Joaquin Martinez Lopez
Journal: Blood (2015)
Improving the health and welfare of people who live in slums
Authors: Richard J Lilford, Oyinlola Oyebode, David Satterthwaite, G J Melendez-Torres, Yen-Fu Chen, Blessing Mberu, Samuel I Watson, Jo Sartori, Robert Ndugwa, Waleska Caiaffa, Tilahun Haregu, Anthony Capon, Ruhi Saith, Alex Ezeh
Journal: The Lancet (2016)
Long-term safety and efficacy of bisphosphonate (BP) therapy for more than 24 months (M) in breast cancer (BC) patients (pts) with bone metastasis (BM)
Authors: I. Kokufu, M. Yamamoto, T. Noda, M. Hiratsuka, H. Nishikawa
Journal: Journal of Clinical Oncology (2005)

816 Background: In BC pts, bone is the most frequent site of distant metastasis. BPs exhibit highly beneficial effects on lytic bone lesions in BC pts. ASCO guidelines on the role of BPs in women with BC suggest that intravenous BPs be continued until evidence of substantial decline in general performance status (PS). However, the safety of continuing BP therapy for a prolonged period has rarely been investigated. We studied the long-term safety and efficacy of BP therapy in BC pts with BM who received BP therapy for more than 24 M as long-term administration. Methods: Pamidronate (PMT) 45mg and incadronate (INC) 10mg were given over 60 min intravenous infusion to BC pts with BM. The dosing interval was every 2 weeks at the start. When an effective response was obtained, BP was given at the interval of every 4 weeks or longer. PMT was given to all pts at the start, then changed to INC when there was no response. All pts received systemic therapy. Laboratory tests were performed at every administration. Adverse events (AEs) were assessed using NIC-CTC. Results: Twenty-one pts received BPs for more than 24 M. Median duration of administration of BPs was 48 M (24∼87 M), and 10 pts received BPs for more than 50 M. Eight pts were changed from PMT to INC. During treatment, there were no pathological fractures observed. No radiation or surgical treatment of bone was performed. Hypercalcemia was detected in 1 pt (4.8%). Lytic bone lesions changed to sclerotic lesions in 13 pts (61.9%). Improvement of PS was detected in 7 pts (33.3%). Hypocalcemia was seen in 13 pts (61.9%) but was not symptomatic. Leukopenia, thrombocytopenia and anemia were not observed. The baseline serum creatinine level was maintained and G1 serum creatinine elevation was seen in 4.8% of pts. G1 fatigue (19.0%), fever (13.3%), headache (4.8%) and diarrhea (4.8%) were detected. Major AEs were mild and transient. Conclusions: Severe AEs of long-term BP therapy were not seen. We conclude that long-term BP therapy was very effective and well-tolerated in BC pts with BM. AEs in this study were fewer than in previous reports. The optimal dose, duration and dosing interval for long-term BP therapy should be determined. No significant financial relationships to disclose.
Efficacy of Orally VP16 Plus Prednisone with or without Cyclophosphamide for Refractory and Relapsed Peripheral T-Cell Lymphoma: A Retrospective Single Center Experience
Authors: Anne-Blandine Boutin, Marjan Ertault de la Bretonnière, Helene Monjanel, Marlene Ochmann, Hélène Doyen, Philippe Colombat, Emmanuel Gyan
Journal: Blood (2014)
Critical role of FoxO3a transcription factor in response to therapy with EGFR inhibitors, gefitinib and lapatinib, in breast cancer
Authors: J. Krol, E. Lam, C. Coombes
Journal: Journal of Clinical Oncology (2007)

21018 Background: Inhibition of the EGF-receptor is a potential therapeutic strategy for breast cancer. The PI3-K/PKB signalling pathway plays an important role in cell proliferation, survival and malignant transformation. The Forkhead box group O transcriptional factor, FoxO3a, is a direct downstream target of PKB. Here we studied the role of the FoxO3a in response to the EGFR inhibitors Gefitinib and Lapatinib. Methods: Response of breast cancer cell lines to treatment with Gefitinib and Lapatinib was evaluated by proliferation assay and FACS analysis. Expression of FoxO3a and its downstream targets was analysed using Western blotting. Sub-cellular localisation of FoxO3a was analysed by confocal microscopy. FoxO3a mRNA level was measured by RTq-PCR. siRNA transfections were performed using Oligofectamine reagent. Immunohistological staining was performed on patient samples to validate our findings. Results: Treatment of a panel of breast cancer cell lines with both inhibitors resulted in decreased proliferation due to G1-arrest and apoptosis in two sensitive cell-lines, BT474 and SKBR3. Western blot analysis revealed that response to the treatment was associated with a decrease in PKB and FoxO3a phosphorylation and thus the nuclear relocalisation of FoxO3a. Confocal microscopy confirmed that treatment induced nuclear translocation of FoxO3a only in sensitive but not resistant cells. This relocation of FoxO3a was accompanied by an induction of FoxO3a mRNA and its principal targets, p27 kip1 and Bim. Transfection of the sensitive BT474 cells with FoxO3a specific siRNA resulted in a significant reduction in FoxO3a protein expression and Gefitinib-induced cell death. Comparison of immunohistochemical staining of biopsies from breast cancer patients before and after Gefitinib treatment revealed that therapy resulted in a significant increase in nuclear FoxO3a staining. Conclusion: Our results demonstrate for the first time that the EGFR-family inhibitors, Gefitinib and Lapatinib, specifically target FoxO3a to induce cell cycle arrest and apoptosis. This finding helps to define the mechanism of action of Gefitinib and Lapatinib and may provide novel insights into the molecular basis for resistance to these inhibitors. No significant financial relationships to disclose.
Exposure to endocrine-disrupting chemicals in the USA: a population-based disease burden and cost analysis
Authors: Teresa M Attina, Russ Hauser, Sheela Sathyanarayana, Patricia A Hunt, Jean-Pierre Bourguignon, John Peterson Myers, Joseph DiGangi, R Thomas Zoeller, Leonardo Trasande
Journal: The Lancet Diabetes & Endocrinology (2016)