tbuckley/cabot-search huggingface dataset:
Hepatocyte Growth Factor Prevents the Development of Chronic Allograft Nephropathy in Rats
Authors: Haruhito Azuma, Shiro Takahara, Kunio Matsumoto, Naotsugu Ichimaru, Jing Ding Wang, Toshiki Moriyama, Ana-Maria Waaga, Masaya Kitamura, Yoshinori Otsuki, Akihiko Okuyama, Yoji Katsuoka, Anil Chandraker, Mohamed H. Sayegh, Toshikazu Nakamura
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Long-term renal isografts in humans and laboratory animals exhibit features similar to those of chronic allograft nephropathy (CAN), indicating that antigen-independent factors, such as acute renal ischemia, are likely to be involved in the development of CAN. Hepatocyte growth factor (HGF) has been demonstrated to play a renotropic role in renal regeneration and protection from acute ischemic injury. This study was thus conducted to investigate the effect of HGF on the development of CAN, using an established rat model. HGF was administered daily (100 μg/d, intravenously) for 4 wk after engraftment. Control animals received saline solution. Allografts from control animals exhibited early evidence of severe structural collapse and necrotic cell death in the proximal tubules and outer medulla, with mononuclear cell infiltration, within 1 wk after engraftment. This was followed by sequential upregulation of adhesion molecules and cytokines, accompanied by dense macrophage infiltration. Fibrogenic events, as indicated by marked increases in transforming growth factor-β1 expression and the accumulation of smooth muscle α-actin, occurred during the same period. Control animals ultimately developed features typical of CAN, with functional deterioration and severe histologic changes; a survival rate of 50.6% by 32 wk was observed. In contrast, remarkably little early injury and no late fibrogenic events were observed for the HGF-treated group. All treated animals survived, with well preserved graft function, during the 32-wk follow-up period. These results indicate that renal protection and recovery from early allograft injury with HGF treatment greatly contribute to a reduction of susceptibility to the subsequent development of CAN in a rat model. The potential application of HGF in the prevention of CAN warrants further attention.
First-In-Human Phase I Trial Assessing the Highly Selective C-Met Inhibitor Msc2156119J (Emd 1214063) in Patients with Advanced Solid Tumors
Authors: G.S. Falchook, D.S. Hong, H.M. Amin, S. Fu, S.A. Piha-Paul, F. Janku, H. Zheng, F. Bladt, A. Johne, R. Kurzrock
Journal: Annals of Oncology (2014)
Original article: Randomized trial of adjuvant chemotherapy for operable breast cancer comparing i.v. CMF to an epirubicin-containing regimen
Authors: L. Mauriac, M. Durand, J. Chauvergne, J.-M. Dilhuydy, F. Bonichon, A. Avril, E. Bussieres, A. Faucher, P. Mage, D. Maree, E. Stockle, J.M. Dilhuydy, J. Pigneux, P. Richaud, L. Thomas, M.H. Dilhuydy, L. Guibert-Tamisier, L. Le Treut, B. Barreau, F. Bonichon, J.M. Coindre, I. de Mascarel, M. Trojani, J. Wafflart
Journal: Annals of Oncology (1992)
Two thirds of rheumatology patients wait too long for assessment, audit finds
Authors: Jacqui Wise
Journal: BMJ (2016)

Two thirds of patients with early inflammatory arthritis are not seen by a specialist within the recommended three weeks of referral, says a national clinical audit of rheumatoid and early inflammatory arthritis in England and Wales.1

The National Institute for Health and Care Excellence’s (NICE) quality statement 2 (Assessment)2 says that patients with early inflammatory arthritis should be seen by rheumatology services for the first time within three weeks of referral. In London 55% of patients’ assessments meet this standard, but in the rest of the country this …
A critical comparison of allogeneic bone marrow transplantation and conventional chemotherapy as treatment for acute nonlymphocytic leukemia.
Authors: C B Begg, P B McGlave, J M Bennett, P A Cassileth, M M Oken
Journal: Journal of Clinical Oncology (1984)

Published data from two centers conducting bone marrow transplantation on patients with acute nonlymphocytic leukemia in first remission were pooled and compared with results from an Eastern Cooperative Oncology Group (ECOG) study in which patients were treated with conventional chemotherapy. A series of adjustments were made to the ECOG sample to account for selection factors that restrict access of patients to transplantation. The transplant sample exhibits considerably higher disease-free survival when compared to the adjusted ECOG series (53% versus 21% at three years). The transplant series is somewhat younger than the ECOG series (median, 24 years versus 28 years). The impact of age on the disease-free survival results is difficult to assess because of the relatively small samples in the different age groups. However, by defining a suitable control group, methodology for making a critical comparison between the two modalities is presented which, if applied to larger samples of patients, should help to resolve the issue. In the absence of data from a large, prospective randomized study, a critical retrospective comparison of available data is essential in the assessment of treatment options.
Rationale for salvage therapy with high-dose selective estrogen receptor modulator after treatment failure of aromatase inhibitors in breast cancer
Authors: S. Saji, M. Hirose, H. Iwase, Y. Yamaguchi, M. Toi, S. Hayashi, K. Kuroi
Journal: Journal of Clinical Oncology (2008)

1129 Background: Aromatase inhibitors (AIs) are currently widely used for hormone responsive breast cancer patients as adjuvant therapy and first line treatment for metastatic breast cancer (MBC). Salvage therapy has become important to the patients failed these primary AIs. We explored the possible application of high-dose selective estrogen modulators (SERMs) in vitro and in vivo. Methods: As a model for treatment failure of AI, MCF-7 cells were cultured in estradiol (E2)-deficient medium for over 6 months. Survived cells were established as MCF-7 long term E2 deprived (LED) clone. Cell counting kit-8 was used for proliferation assay, and transcription activity of Estrogen Receptor (ER) on estrogen-responsive element (ERE) was measured with luciferase assay. HI-FAIR study (n=63) was conducted as a retrospective chart review from nine Japanese institutes for demonstrating the possible efficacy of high-dose toremifene (120mg/day p.o.) after AI treatment failure in MBC patients. Results: In western blotting, MCF-7 LED clone showed increased expression of ER and Her2, and reduction of Progesterone Receptor (PR) expression as compared to parent MCF-7 cell. Although addition of various concentration of E2 did not enhance the proliferation of LED cell, ERE-dependent transcription was still activated by E2 in same degree as parent MCF-7. Of note was 30-fold increase of basal transcriptional activity in LED cell due to phosphorylation of ER. Fulvestrant (FUL), 4-OH Tamoxifen (TAM) and Toremifene (TOR) all inhibited growth of LED cell. IC50 of FUL for parent MCF-7 and LED cell are identical, and maximum inhibition ratio was about 65%. Whereas, TAM and TOR showed more favorable response to LED cell than to parent MCF-7 cell. Growth capability of LED cell was reduced by about 90% by both TAM and TOR in dose dependent manner. In HI-FAIR study high-dose TOR showed 14.3% response rate, 34.9% clinical benefit and 7.4 months median TTF as the first (n=4), second to third (n=40) and fourth (n=19) lines MBC therapy after AI treatment. Conclusions: Although the efficacy of FUL in the patients previously treated with Ais has been already reported, this study demonstrated the possible contribution of high-dose SERM for these patients. No significant financial relationships to disclose.
Impaired Neurite Contact Guidance in Ubiquitin Ligase E3a (Ube3a)-Deficient Hippocampal Neurons on Nanostructured Substrates
Authors: I. Tonazzini, S. Meucci, G. M. Van Woerden, Y. Elgersma, M. Cecchini
Journal: Advanced Healthcare Materials (2016)

Recent discoveries indicate that during neuronal development the signaling processes that regulate extracellular sensing (e.g., adhesion, cytoskeletal dynamics) are important targets for ubiquitination-dependent regulation, in particular through E3 ubiquitin ligases. Among these, Ubiquitin E3a ligase (UBE3A) has a key role in brain functioning, but its function and how its deficiency results in the neurodevelopmental disorder Angelman syndrome is still unclear. Here, the role of UBE3A is investigated in neurite contact guidance during neuronal development, in vitro. The microtopography sensing of wild-type and Ube3a-deficient hippocampal neurons is studied by exploiting gratings with different topographical characteristics, with the aim to compare their capabilities to read and follow physical directional stimuli. It is shown that neuronal contact guidance is defective in Ube3a-deficient neurons, and this behavior is linked to an impaired activation of the focal adhesion signaling pathway. Taken together, the results suggest that the neuronal contact sensing machinery might be affected in Angelman syndrome.
Prognostic value of clinicopathological factors in operated stage I non-small cell lung cancer (NSCLC)
Authors: R. Nakahara, H. Suzuki, H. Matsuguma, S. Igarashi, N. Miyazawa
Journal: Journal of Clinical Oncology (2006)

7222 Background: Recently adjuvant chemotherapy has improved survival in resected stage I, especially stage IB NSCLC. While some cases with stage IA NSCLC have poor prognosis, there are no reliable clinicopathological markers to predict cancer related death. This study was conducted to identify the prognostic factors for resected stage IA and IB patients. Methods: We retrospectively analyzed 318 cases that were diagnosed with pathological stage I NSCLC from 1986 to 2000 at Tochigi Cancer Center. Various clinical and pathologic factors were reviewed, and the risk of a cancer related death was investigated. Analyzed factors were as follows: sex, age, smoking status, preoperative serum CEA level, tumor histological type, pathological differentiation, tumor size, lymphatic invasion (ly), vascular invasion (v), and pleural invasion (p). Results: The cancer specific 5-year survival rate for each stage were estimated to be 91% foe stage IA (n = 198) and 66% for stage IB (n = 120). In the stage IA subset, the univariate analysis revealed the following five factors to be poor prognostic factors: age 65 &lt; (p = 0.008, Risk Ratio = 1.76), high CEA level (p &lt; 0.001, RR = 2.09), tumor size 2 cm &lt; (p = 0.008, RR = 1.75), ly (+) (p = 0.007, RR = 1.87), and v (+) (p = 0.003, RR = 1.77). The 5-year survival rate for stage IA patients that have three or more factors was 67% (n = 43). In the stage IB subset, the univariate analysis of clinicopathological factors revealed tumor size 4 cm &lt; (p = 0.004, RR = 1.53), v (+) (p = 0.02, RR = 1.45), and no pleural invasion (p0) (p = 0.004, RR = 0.64) to be prognostic factors. The 5-year survival rate for stage IB patients that have all the good prognostic factors (tumor size 4 cm ≥, v(-), and p0) was 96% (n = 26). Conclusion: Our analysis suggests that the combination of prognostic factors revealed the poor prognostic group equal to stage IB patients in stage IA group. On the other hand, combination of prognostic factors revealed the good prognostic group in stage IB patients. It should be considered to do adjuvant chemotherapy with poor prognostic stage IA patients and avoid with good prognostic stage IB patients. No significant financial relationships to disclose.
Acute promyelocytic leukaemia with t(15;17) following treatment of Hodgkin's disease - a report of 4 cases
Authors: S. Gillis, O. Sofer, O. Zelig, E.J. Dann, H. Lotan, D.Ben Yehuda, R. Isacson, E.A. Rachmilewitz, I. Ben-Bassat, A. Polliack
Journal: Annals of Oncology (1995)
Role of synuclein-γ in perineural invasion in a mouse pancreatic cancer model and use as a marker of prognosis
Authors: T. Hibi, T. Mori, M. Fukuma, M. Sakamoto, T. Kubota, M. Kitajima, Y. Kitagawa
Journal: Journal of Clinical Oncology (2008)

4634 Background: Perineural invasion (PNI) is responsible for the high incidence of locoregional recurrence and dismal prognosis in pancreatic cancer. We recently established a mouse PNI model and differentiated human pancreatic cancer cell lines exerting high and low PNI. This study was aimed to compare protein expression profiles between these 2 subsets to discover promising molecule critically involved with PNI and to elucidate its role in vivo and surgical cases. Methods: Quantitative proteomics were compared with DNA microarray to detect up-regulated proteins that correlate with the increase of their corresponding RNA levels. To evaluate the clinical significance of the overexpressed molecule, namely synuclein-γ, we retrospectively reviewed the medical records of 62 resected cases of pancreatic cancer. The effect of stable synuclein-γ suppression with short hairpin RNA was examined in vitro and by mouse PNI/orthotopic transplantation models. Results: Synuclein-γ messenger RNA level was extremely elevated in the high perineural invasion group (p = 0.0001). In surgical cases, synuclein-γ overexpression correlated with major invasive parameters including perineural invasion and advanced stage (p < 0.05). Multivariate analyses revealed synuclein-γ overexpression to be the only independent predictor of diminished overall survival (hazard ratio, 3.4; p = 0.003) and the strongest negative indicator of disease-free interval (hazard ratio, 2.8; p = 0.011). Stable synuclein-γ suppression dramatically reduced perineural invasion (p = 0.009) and liver/lymph node metastasis (p < 0.05) in mouse models. Conclusions: This is the first study to provide in vivo evidence that synuclein-γ is critically involved with perineural invasion and a biomarker of highly malignant potential in pancreatic cancer. Synuclein-γ is also a significant prognostic factor of decreased overall and disease-free survival; it may serve as a potential molecular target of anticancer therapy. No significant financial relationships to disclose.
Nipple-sparing mastectomy and subareolar biopsy: To freeze or not to freeze?
Authors: Michael Alperovich, Keith M. Blechman, Fares Samra, Richard Shapiro, Deborah M. Axelrod, Mihye Choi, Nolan S. Karp, Amber Azniv Guth
Journal: Journal of Clinical Oncology (2012)

185 Background: Advances in breast cancer screening and treatment have fostered the use of surgical procedures that increasingly optimize cosmetic outcome, while ensuring oncologic safety remains the primary concern of the oncologic surgeon. The role of nipple-sparing mastectomy (NSM) for risk-reducing surgery and breast cancer is evolving. It can be difficult to demonstrate involvement of the nipple-areolar complex (NAC) preoperatively, and and in this report we examine the utility of intraoperative subareolar frozen section (FS). Methods: Records of patients undergoing NSM at the NYU Langone Medical Center from 2006-2011 were reviewed retrospectively. Use of subareolar FS was at surgeon’s discretion. Results: 237 NSM were performed (146 prophylacytic, 91 theraputic). FC was not utilized in 58 mastectomies (28 prophylactic), with 2 (+) on paraffin. Among the remaining 180 mastectomies, 11 biopsies were (+)(7.2%); 5 subareolar biopsies were (+) on FS and paraffin histologic slides (PS) (2.8%); 6 were negative on FS and (+) on PS. Among the 3 prophylactic NSM with (+) subareolar biopsies there was 1 (+) FS, 1 (-) FS, and 1 with no FS performed. There were no false (+) FS. Four of the 5 patients with (+)FS underwent simultaneous excision of the NAC. The 5th patient had atypia on FS and DCIS on PS, and returned to the OR during the same hospitalization for removal of NAC. The remaining patients underwent subsequent excision of the NAC either during planned 2nd stage reconstruction or following completion of chemotherapy. 8 NAC were free of disease and 5 were positive for in situ or invasive disease. There has been no local recurrence in these patients to date. Conclusions: The rate of NAC involvement is low, 5.5% in this series, and FS, while utilized in the majority of these cases, detected only 46% of subareolar disease. While FS can direct intraoperative decision making, the predictive power is low, and these considerations must be addressed in preoperative patient discussions. Furthermore, among those patients with (+) subareolar biopsies, only 39% had residual disease on NAC excision. Thus, optimal oncologic management of the NAC must still be considered an unresolved issue.
Glucolysis During Culture of Neoplastic and Non-Neoplastic Murine Cell Lines Under Aerobic and Anaerobic Conditions
Authors: Katherine K. Sanford, Benton B. Westfall, Jay L. Jackson
Journal: JNCI Journal of the National Cancer Institute (1970)

In a previous study the glucolytic rates of 3 murine clones were significantly increased under anaerobic as compared with aerobic conditions. These clones originated from 1 common cell derived from a culture of subcutaneous connective tissue taken from an adult C3H mouse. The clones had undergone neoplastic conversion during culture. Under anaerobic conditions 1 mole of glucose is reputed to yield 2 moles of lactic acid to give a molar ratio of 2 (lactic acid:glucose). However, in all assays on the 3 clones, the molar ratio was approximately 1. One objective of the present study was to ascertain whether a low molar ratio might be characteristic of neoplastic cells in long-term culture. Another objective was to look for any differences in glucolytic rates between neoplastic and non-neoplastic cells in culture. A neoplastic and 2 non-neo-plastic cell lines derived from C3Hf mouse embryos were examined with respect to their glucolysis under both aerobic and anaerobic conditions. Under anaerobic conditions, no increase in cell numbers occurred, glucolytic rates were significantly increased, and molar ratios were not 1 but approached 2 (average = 1.9 for 30 cultures). There was some evidence under anaerobic conditions of a higher rate of glucolysis by the neoplastic cells as compared with 1 line of non-neoplastic cells.
Abstract 11310: SR Ca2+ Leak is Temperature[[Unable to Display Character: –]]Sensitive: Rol of the Nitroso-Redox Balance
Authors: Raul A Dulce, Vera Mayo, Erika B Rangel, Wayne Balkan, Joshua M Hare
Journal: Circulation (2013)

The role of neuronal NO synthase (NOS1) in regulating sarcomeric reticulum (SR) Ca2+ leak, which impairs Ca2+ cycling and contractile dysfunction of the heart, remains highly controversial. Leak is...
Differences in palliative care needs among cancer survivors in an inner city academic facility versus a suburban community facility.
Authors: Alison Lutz, Rachel Regn, William Robinson, William R. Robinson
Journal: Journal of Clinical Oncology (2015)

61 Background: To determine differences in palliative care (PC) needs in newly diagnosed cancer patients from an inner-city academic facility compared to a suburban, community facility. Also, to identify ways to improve PC for cancer patients in these locations. Methods: 270 subjects with cancer were prospectively identified, 85 from an inner city academic facility (Site A), and 185 from a suburban community facility in the same metropolitan area. (Site B) All patients received treatment from board-certified oncologists. Master’s level Social Workers asked all subjects to complete a standardized, validated questionnaire to determine their palliative care needs prior to treatment. Completed questionnaires were collected and data was depersonalized and analyzed by the authors. Statistical differences were assessed using standard methods. Results: Site A patients were younger (56.3 vs 61.5years) less likely to be caucasian (35/85, 41.2% vs 114/185, 61.6%) and less likely to have private insurance (28/85, 32.9% vs 187/185, 47%). Site B patients were more likely to express a fear of pain, (112/185, 60.5% vs 28/85,32.9%) dying, (112/185, 60.5% vs 18/85, 21.2%) being alone, (112/185(60.5% vs 15/85, 17.7%) or nausea (117/185, 63.2% vs 10/85, 11.8%). Site A patients were more likely to express fear of not having transportation, (35/85, 41.2% vs 42/185, 22.1%) inability to pay for prescriptions, (28/85, 32.9% vs 40/185, 21.6%) or child care (13/85, 15.3% vs 9/185, 4.9%). All differences were significant at a p &lt; 0.05. Conclusions: There are major differences in the PC needs of patients presenting to an inner-city academic vs suburban community facility. To be most effective, PC programs must be tailored to the community. Interventions proposed for the suburban community facility include early access to: 1) grief counseling, 2) support groups, 3) Nurse-Navigators. Interventions proposed for the inner city academic facility include early access to: 1) Medication cost assistance programs (local philanthropies, facility-based pharmacy discounts) 2) travel services (cab vouchers, coordination with public transportation schedules) 3) on-site child care facilities.
Evaluation of anticancer drugs in NSCLC
Authors: H. M. Guirgis
Journal: Journal of Clinical Oncology (2009)

e14616 Background: Methodology to evaluate anti-cancer drugs in GI malgnancies was previoulsy reported. It has been estimated that the society would be willing to pay $50,000-$100,000 per life-year S gain (S Negrier et, 2007). Objectives: Design scoring model methodology to evaluate and grade anti-cancer drugs in NSCLC with emphasis on the association between between S, AEs, A and C. Methodology: 0S and AEs data were abstracted from J Douillard, R Herbert, Le Chevalier, C Mangeold, A Sandler, F Shepard, R Rossell and C Thienelt (2005–2008). A was graded in points (P) from 3 oral to zero daily injections. AEs: 4 (placebo) to 0 (fatalities) using CTCAE v 3.0. S gain (days,d) was calculated in a corrected ratio of S/360 (SR); Cost R: as C/d/s/$1500, divided by (A+ AEs), corrected and expressed as C scores. C in US $ was based on treating one patient for entire course,70 kg or 1.7/ m2. Using a grading scale from A to D, Survival &gt; 360d, SR&gt;10; C/d/s up to $63 and CR up to 4.2 were rated as (A+) while S&lt; 15d, SR &lt;0.42, C/d/s&gt; $1500 and CR&gt;100 as (D). Results: Examples shown in Table . Adj Cis + Vin after resection in stage II and III scored the highest SR and lowest CR with A+ rating. However, there was a lesser SR using the same combination in mNSCLC. OS markedly improved with Er and BV in 2nd-line. Addition of Cetuximab (Cet) to Cis and Vin demonstrated modest S gain at a much higher CR. Bevacizumab (BV) combined with Pac + Car improved OS over Pac + Car in 1st and 2nd lines at higher CR. Combination of BV, Cis and Gemcitabine demonstrated the lowest S, highest CR and D rating. Discussion: S and C were calculated as Ratios. C scores were based on the association of S with arbitrary but relative weights assigned to AEs and A. BV and Er improved OS in 2nd line, in contrast to phase III Beta study. Adjuvant Cis+Vin seems to be cost-effective. Increased CR was not necessarily associated with improved S. Grading of drugs varied depending on S or C. Higher C/d/s, increased AEs and cumbersome A resulted in higher C scores. Conclusions: SR, CR and possibly C scores might be advantageous in evaluation, grading and comparison of anti-cancer drugs. [Table: see text] No significant financial relationships to disclose.