bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitigating smoothened inhibitor-induced growth plate closure with parathyroid hormone.
Authors: Timsit Yoav E , Gunson Diane E , Krucker Thomas , Markovits Judit E , Buonamici Silvia , Boral Anthony , Amakye Dereck Dokyi , Nelson Aaron L , Pognan Francois , Chibout Salah-Dine , Turner Nancy A ,   Novartis Institutes for BioMedical Research Inc.
Published: March 2020

9562 Background: The Hedgehog pathway plays an important role in regulating growth plate patency by activating PTH/PTHrP signaling, and loss of PTH/PTHrP signaling is an expected pharmacological effect of smoothened (Smo) inhibition. LDE225, a Smo inhibitor currently in phase I/II trials for the treatment of basal cell carcinoma (BCC) and medulloblastoma (MB), causes closure of the epiphyseal (growth) plate in rodents and dogs. As a therapeutic strategy to mitigate these effects, we investigated whether administration of human parathyroid hormone (PTH amino acids 1-34 or PTH1-34) could prevent premature growth plate closure caused by LDE225. Methods: Oral LDE225 was given once daily to rapidly growing male rats (starting at 4 or 6 weeks of age) in combination with hPTH1-34 administered subcutaneously as a continuous infusion (to mimic signaling by locally-produced PTHrP) or as once-daily injections. Femur and tibial growth plates were scanned by microCT and growth plate volumes were calculated. Growth plates were also assessed histologically. Results: Continuous delivery of hPTH1-34 provided the greatest effect for maintaining patent growth plates compared to once-daily subcutaneous injections. However, the dose of continuous hPTH1-34 giving the greatest protection was not well-tolerated beyond 1 week due to PTH-induced hyperparathyroidism, confirmed by clinical chemistry and histological assessment. Reduction in the dose of continuous hPTH1-34 improved tolerability, but provided less protection to the growth plate. Once-daily hPTH1-34 injection for two weeks was well-tolerated, with anabolic effects clearly observed by histology and microCT. The extent of closure in animals co-treated with LDE225 and once-daily hPTH1-34 injections was less compared to that caused by LDE225 treatment alone. Conclusions: As shown in this preclinical model, hPTH1-34 administration mitigates LDE225-induced growth plate closure. Although hPTH1-34 shows promise experimentally, current use is restricted in pediatric patients and further study will be needed before considering hPTH1-34 treatment concurrent with LDE225 therapy in children or adolescents.
Cell cycle and apoptosis regulatory protein (CARP)-1 expression in neuroblastoma.
Authors: Hanmod Santosh S. , Siegel Samantha , Hatfield James , Levi Edi , Zidan Marwan , Rabah Raja , Ravindranath Yaddanapudi , Rishi Arun K , Wang Zhihong Joanne 
Published: March 2020

9578 Background: Neuroblastoma (NB) is the most common extra-cranial solid tumor in children. The prognosis for patients with high risk NB is still poor. Study of additional prognostic factors will enhance current understanding of the tumor biology and risk stratification. CARP-1 is a recently identified molecule mediating apoptosis signaling by agents like doxorubicin and etoposide. Since these agents are used in the front line treatment of NB, we tested whether CARP-1 expression could be another prognostic factor in NB. Methods: CARP-1 expression was examined by Western blot in a pair of NB cell lines, SK-N-SH and SK-N-SH Dox. We reviewed medical records of patients with NB at Children’s Hospital of Michigan from 2000-2009 and examined CARP-1 expression by immune-histochemistry in the archived, formalin fixed paraffin embedded NB tissues. CARP-1 expression was recorded as positive or negative. Correlation of CARP-1 expression and progression free survival (PFS) was calculated. Results: CARP-1 expression was detected in SK-N-SH but not SK-N-SH Dox, a doxorubicin-resistant derivative of SK-N-SH, suggesting that resistance to doxorubicin is associated with decreased level of CARP-1 expression in NB cells. Of the 30 cases studied, 53 % (16/30) expressed CARP-1. There was no significant difference in N-myc amplification status (13% vs.14%, p=0.3), or proportion of unfavorable Shimada histology (60% vs. 64%, p=0.5) between CARP-1 positive vs. negative groups. Twenty three percent (7/22) patients progressed or relapsed, including 2/16 (13%) in CARP-1 positive group vs. 5/14 (36%) in CARP-1 negative group (p=0.1). There was no significant difference in the PFS at 1 year (94% vs.79%, p=0.2) and 3 year (86% vs.71%, p=0.2) between CARP-1 positive vs. negative groups. Conclusions: CARP-1 expression was decreased in doxorubicin resistant NB cell line. CARP-1 expression was detected in approximately half (53%) of NB tumors. Patients with NB who expressed CARP-1 showed trend towards better 1- & 3-year PFS as compared to those who did not express CARP-1, however, the results are not statistically significant which could be due to the small sample size. Further study with a larger number of patients is warranted to clarify these findings.
Assessment of peripheral blood T regulatory cells (Tregs) in PNET/Ewing sarcoma: A prospective study.
Authors: Tvsvgk Tilak , Sharawat Surender Kumar , Gupta Ritu , Agarwala Sandeep , Khan Shah Alam , Rastogi Shishir , Vishnubhatla Sreenivas , Bakhshi Sameer 
Published: March 2020

9580 Background: Tregs in bone marrow have been previously evaluated in PNET patients; however, data on peripheral blood ccirculating Tregs is lacking. The objective of our study was to determine baseline Treg frequency in PNET patients and correlate the same with patient characteristics and outcome. Methods: Samples of 5ml venous blood were obtained from 38 newly diagnosed PNET patients at diagnosis along with six healthy controls. Flow cytometric analysis was done for detecting Treg cells [CD4+CD25+FoxP3+]. Results: Thirty-eight patients with median age 17 years; male/female ratio of 5.5:1 had significantly higher baseline Tregs than healthy controls [9.17%±.3.08 vs 3.16±1.49%; p=<0.0001]. Eight patients (21.1%) had fever at baseline presentation. The disease was extra-skeletal in one and metastatic at baseline in 11 (28.9%) patients. Ten patients relapsed on standard protocol of therapy and seven died. The median Treg frequency was 8.84% (Range: 2.49-16.31). When the Tregs were categorized as high and low based on the median value, patients with fever had a significantly higher Tregs than those without fever [11.3%±.3.5% vs 8.6% ±. 2.7%; p=0.02]. No significant association of peripheral blood Treg cells frequency was noted with other factors like age, sex, metastatic disease, relapse or death. The EFS was 55% and OS 70% of the entire cohort at a median follow up of 14 months. There was no significant difference in the EFS or OS between the high and low Treg cell groups [EFS- 52% vs 64%; p=0.99 and OS-75% vs 70%; p=0.26]. Conclusions: This is the first study on circulating Tregs in PNET, and it shows that the peripheral blood Treg frequencies are higher in these patients as compared to healthy controls. Further, PNET patients with fever had significantly higher Treg frequency. However, Tregs did not differ with respect to metastatic disease at presentation, EFS or OS.
Trends in survival of childhood solid tumors diagnosed 1985-2008 in the Nordic countries.
Authors: Cvancarova Milada , Jonsson Olafur G. , Schroder Henrik , Perkkio Mikko , Gustafsson Goran , Wesenberg Finn ,   Nordic Society of Paedric Haematology and Oncology
Published: March 2020

9590 Background: Classification of childhood solid tumors differs greatly from tumors diagnosed in adults. Thus establishment of childhood cancer registries is essential to monitor changes and progress in cancer care. Methods: All individuals born in the Nordic countries are allocated a unique ID number and have access to comprehensive health care services. Further, it is required by law that all new cases of cancer are reported to cancer registries. This makes it possible to achieve almost complete registration of all cancer cases and their status together with information regarding the cancer tumour and its treatment. Status registrations were made partly from national population registries and partly from death registries only, as conditions differ between countries. Crude survival was modelled using the Kaplan-Meier method stratified by selected diagnostic groups, age groups and diagnostic period. The crude estimates were compared with log-rank tests. Results: In total, 12,343 children <15 yrs of age were diagnosed with cancer during 1986-2010 in the Nordic regions (Denmark, Finland, Iceland, Norway, Sweden) and classified according to Birch & Marsden classification. Data were collected at the NOPHO solid tumour registry located at the Cancer Registry of Norway. The overall incidence for the whole period was 11.2 per 100,000 children per year. The overall 5-year survival for all solid tumours reached 80.0 %, 95% CI [79.3 to 80.7] %. There was a significant increase in survival for those diagnosed after 1991, p < 0.001. Children diagnosed when older than 10 years reached higher 5-yrs survival than those diagnosed <5 yrs, 82.4% and 78.3%, respectively. The highest 5-yrs survival was seen for retinoblastoma (97.0%), germ.cell neoplasm (90.8%), renal tumours (88.3%) and lymphomas (88.2%). The lowest 5-yrs survival was observed for sympathetic nervous system (65.4%). The highest increase in survival was seen for non-Hodgkin lymphoma pts, 77.2% diagnosed 1986-1990 vs. 85.9% diagnosed 2001-05. Conclusions: There has been some improvement in survival in recent time periods, especially for some diagnoses. However, there were no changes in overall survival wrt sex and only very limited changes in overall survival by age groups.
Bleomycin-associated lung toxicity in childhood cancer survivors.
Authors: Zorzi Alexandra Patricia , Yang Connie L , Dell Sharon , Nathan Paul C. 
Published: March 2020

9591 Background: Bleomycin has been established as a pulmonary toxin, but the risk for toxicity in survivors of childhood cancer is poorly characterized. Methods: We conducted a cross-sectional study of lung function in survivors of childhood Hodgkin lymphoma and germ cell tumor treated with bleomycin at our institution between 1997 and 2010. We assessed their most recent post-therapy pulmonary function test (PFT). Spirometry and lung volumes were categorized as normal, restrictive, obstructive or mixed. Diffusing capacity of carbon monoxide (DLCO) was categorized as normal or abnormal. Results: 195 patients were treated with bleomycin. Ten died of non-pulmonary causes. Of 185 survivors, 143 (77%) had complete data available for analysis. Median cumulative bleomycin dose was 60U/m2 (IQR 30-60). Three patients (2%) had a history of acute bleomycin toxicity. PFTs were performed a median of 2.3 years (IQR 1.4-4.9) from completion of therapy. Spirometry was abnormal in 58 patients (41%); of whom 5 (9%) had respiratory symptoms. 42 (70%) had obstructive, 11 (18%) restrictive and 5 (9%) mixed ventilatory defects. Abnormalities were mild in 53 (91%), moderate in 3 (5%) and severe in 2 (4%). DLCO was abnormal in 27 patients, 26 (96%) of whom had mildly reduced DLCO and were asymptomatic. Univariate analysis did not demonstrate a significant association between gender, smoking, lung metastases, lung radiation, chemotherapy regimen, or autologous transplant and abnormal lung function. Disease relapse was associated with abnormal lung function (p=0.01). Smoking (p=0.04) and relapse (p=0.03) were associated with abnormal DLCO. The odds ratio of developing abnormal spirometry for each 1unit/m2 increase in bleomycin was 1.01 (95% CI 1.00-1.02, p=0.07). Conclusions: Childhood cancer survivors treated with bleomycin frequently have evidence of asymptomatic abnormalities on PFT. The current recommendation for pulmonary function testing in childhood cancer survivors appears justified.
CALGB 40502/NCCTG N063H: Randomized phase III trial of weekly paclitaxel (P) compared to weekly nanoparticle albumin bound nab-paclitaxel (NP) or ixabepilone (Ix) with or without bevacizumab (B) as first-line therapy for locally recurrent or metastatic breast cancer (MBC).
Authors: Rugo Hope S. , Barry William Thomas , Moreno-Aspitia Alvaro , Lyss Alan P. , Cirrincione Constance , Mayer Erica L. , Naughton Michael , Layman Rachel M. , Carey Lisa A. , Somer Robert A. , Perez Edith A. , Hudis Clifford , Winer Eric P. 
Published: March 2020

CRA1002 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Monday, June 4, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Regional screening network for characterization of the molecular epidemiology of non-small cell lung cancer (NSCLC) and implementation of personalized treatment.
Authors: Zander Thomas , Heukamp Lukas Carl , Bos Marc Christiaan Allardt , Fassunke Jana , Mattonet Christian , Merkelbach-Bruse Sabine , Ko Yon-Dschun , Schlesinger Andreas , Brockmann Michael , Serke Monika , Gerigk Ulrich , Hekmat Khosro , Engel-Riedel Walburga , Stoelben Erich , Reiser Marcel , Schulz Holger , Schmitz Stephan H. , Frank Konrad , Buettner Reinhard , Wolf Juergen 
Published: March 2020

CRA10529 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Monday, June 4, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Patterns of decision making about cancer clinical trial participation among the online cancer treatment community: A collaboration between SWOG and NexCura.
Authors: Unger Joseph M , Hershman Dawn L. , Burg Kenda , Moinpour Carol , Albain Kathy S. , Petersen Judith A. , Crowley John 
Published: March 2020

CRA6009 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Sunday, June 3, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News
Discordance between Oncotype Dx and Saint Gallen criteria, Adjuvant!, NCCN 2011 guidelines, and initial physician treatment recommendation.
Authors: Pereira Allan Andresson Lima , Santini Fernando Costa , Shimada Andrea Kazumi , Nascimento Ellen Caroline , Katz Artur , Mano Max S. 
Published: March 2020

e11014 Background: The Oncotype Dx recurrence score (RS) assay quantifies the risk of distant recurrence (rDR) and its use has increased despite the lack of prospective studies. Methods: This is a cross sectional retrospective study of consecutive patients (PTS) from our institution with histologically confirmed invasive breast cancer who underwent surgery with curative intent and in whom Oncotype was performed. The main objectives were to compare (1) the predicted rDR by RS and Adjuvant! (2) Risk allocation by RS and St Gallen Criteria, (3) chemotherapy indication according to RS results and NCCN guidelines and (4) to evaluate the impact of RS results on the recommendation of adjuvant chemotherapy (aCT). Results: Between October/2006-June/2011, 74 PTS were evaluated. Forty seven (63,5%) were EC IA and all had estrogen receptor positive; axillary lymph node involvement was seen in 19 PTS (13 micro and 6 macrometastasis). The rDR by RS was low in 50 PTS (67%), intermediate in 19 (26%) and high in 5 (7%). According to Saint Gallen, 7 (9%), 51 (69%) and 14 PTS (19%) were classified as low, intermediate and high risk, respectively. There was a statistical significant discordance between risk allocation according to RS and Saint Gallen (Kappa coefficient=-0.002; p=0.971). Among the 55 node-negative PTS, there was also a statistical significant discordance between the predicted average rDR, obtained from Oncotype, and Adjuvant! with median risk of 8,5% vs 15,7%, respectively (p = 0.00001 rank sum Mann Whitney test). The NCCN 2011 would have indicated aCT to 62 PTS. Among 55 classified as low and high risk by RS, the NCCN would have indicated aCT to 46 PTS. In other words, 89% (41) of PTS who would receive aCT by NCCN were classified as low risk by RS, with a statistically significant discordance (Kappa coefficient=0.035, p=0.328). Conclusions: Oncotype changed the medical management in 28 (55%) of 51 PTS in which the initial intention of the physician was known. Of these, 93% were spared aCT. We found no statistical significant concordance among the Saint Gallen, Adjuvant! or NCCN guidelines with Oncotype Dx. The rDR may be overestimated by clinicopathological-based classifications.
Impact of obesity in postmenopausal early breast cancer patients receiving frontline adjuvant aromatase inhibitors.
Authors: Sahin Ugur , Petekkaya Ibrahim , Arslan Cagatay , Sarici Saim Furkan , Solak Mustafa , Keskin Özge , Ozisik Yavuz Yasin , Altundag Kadri 
Published: March 2020

e11020 Background: Aromatase inhibitors (AIs), anastrozole (ANA) and letrozole (LET), have been shown to be more effective than tamoxifen in the adjuvant treatment of postmenopausal hormone receptor positive breast cancer. However, data from preclinical studies and subgroup analyses of some major clinical trials suggest differring efficacy among AIs. Yet the best clinical choice is still not very clear. This retrospective study aims at comparing the results of treatment with either AI among different subgroups of patients, especially among the obese patients. Methods: Between 2006-2011, 335 women with stage I to IIIC hormone receptor positive postmenopausal breast cancer treated with either ANA or LET as adjuvant treatment were included. Body mass index (BMI), estrogen and progesterone receptor (ER and PR) and HER-2 status at the time of diagnosis were recorded. Patients were grouped as BMI ≤ 30 and BMI > 30. The Kaplan-Meier survival estimates were calculated. Subgroups were compared with the log rank test. A 5 % type-I error was used to infer statistical significance. Results: The percentage of patients receiving ANA or LET were 47.2% and 57.8%, respectively. Median age at diagnosis was 58 (42-84) and lower in the ANA group (p=0.04). Stage II to IIIC disease was present in 76.8 % and the distribution was similar between ANA and LET (p=0.84). Median time of follow-up was 29 months (6-124) and median duration of hormonotherapy was 29 months (3-68) and similar between two groups (p=0.52 and p=0.55, respectively). Of the patients 41.2 % had a BMI of > 30. There was no significant difference in overall (OS) and progression-free (PFS) survivals between ANA and LET (p=0.08 and p=0.94, respectively). However, among patients with a BMI of > 30 a statistically insignificant benefit in PFS was observed with LET (p=0.1). ER, PR and HER2 status had no significant impact on OS and PFS. Conclusions: In a median follow-up of 29 months letrozole and anastrozole yielded similar OS and PFS. However, among patients with a BMI of > 30, LET might bring about a PFS advantage. In selected obese patients LET might be a reasonable choice in this setting. Larger studies with long term follow-up are needed to reach an exact conclusion.
Incidence of reversible amenorrhea in women with breast cancer undergoing adjuvant anthracycline and taxen-based chemotherapy.
Authors: Wang Jiayu , Xu Binghe , Li Qing , Yuan Peng , Ma Fei , Luo Yang , Fan Ying , Zhang Pin , Cai Ruigang 
Published: March 2020

e11025 Background: To determine the incidence of reversible amenorrhea in women with breast cancer undergoing adjuvant anthracycline and taxane-based chemotherapy. Methods: We studied the incidence and duration of amenorrhea induced by adjuvant chemotherapy(regimens: 6EC(Epirubicin and cyclophosphamide) or 4EC follow by 4Taxen) in 68 premenopausal patients with different age group. Reversible amenorrhea was defined as recovery of regular menses or premenopausal hormone values (luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol) in the year following the end of chemotherapy. Results: The incidence of chemotherapy-induced amenorrhea(CIA) at the end of chemotherapy was similar in the two groups: 81.3% in the 6EC arm and 86.3% in the 4EC/4T arm. The incidence of CIA was not significance higher in the middle age arm(older than 40 years old) than in the younger arm(40 or younger than 40 years old): 97.4% versus 86.7% (P=0.114). However, more reversible amenorrhea was observed in younger arm than in middle age arm (76.7% vs. 34.2%, P=0.001). The median duration of regular menses recovering was 9 months in the younger arm and 11 months in the median age arm. More persistent amenorrhea had been detected in the middle age arm than in younger arm: 63.2% vs.10%, P<0.001). Multivariate analysis showed that age (>40years) was independently associated with the incidences of CIA (P=0.048). Conclusions: Age was the strongest predictor of the incidence of amenorrhea during adjuvant chemotherapy. Our study suggests that most of CIA in younger patients induced by adjuvant chemotherapy were reversible amenorrhea. Therefore adjuvant aromatase inhibitors for early breast cancer patients with CIA should be cautiously administered.
Anti-estrogenic effect of TAS-108 in breast cancer cell lines.
Authors: Kim Hadong , Choi Young , Kim Tae-Hoon 
Published: March 2020

e11029 Background: TAS-108 (TAS) is an antiestrogen that binds to both ERα and ERβ and inhibits both estrogen-dependent and independent tumors and TAM resistant tumors. Breast cancer cell lines (BCC) with different pheno- and genotypes are reasonably acceptable models of in vivo breast cancer cell behavior. Thus, we have investigated anti-estrogenic activity of TAS on BCC in the presence of diarylpropionitrile (DPN), a pure ERβ agonist to find ERβ role in TAS activity. Methods: Cultured cells of (1) MCF-7 and ZR-75 (luminal epithelial cells), (2) BT-474 and SK-BR-3 (weakly luminal epithelial cells), and (3) MDA-MB-231 and Hs578T (invasive, mesenchymal-like cells) were treated with: (1) increasing concentrations of DPN or E2, (2) 100nM of 4-hydroxytamoxifen (4-HT) or TAS, and (3) 100nM of DPN or E2 with increasing concentrations of either 4-HT or TAS. After 6 days, cell proliferation was analyzed. The mRNA levels of ERβ and ERα isoform were determined by RT-qPCR. ERα, PR, and Her-2 status was determined by IHC. Percent proliferation compared to the control was calculated and P <0.05 based on T-test was considered significant. Results: The most significant proliferation and growth inhibition was seen in MCF-7 BCC. In the presence of DPN, IC50 (50% inhibitory concentration) was 12.5nmol of TAS vs 33.1nmol of 4-HT. In the presence of E2, IC50 was 2.15 nmol of TAS vs 49.7nmol of 4-HT. Other BCC showed insignificant or variable proliferative and inhibitory response. Overall, DPN displayed high proliferation in most BCC. TAS exhibited higher growth inhibition than 4-HT. Conclusions: Variable responses of different BCC lines to ERα and ERβ agonists and antagonists may be instructive in modeling in vivo breast cancer response to these compounds. Overall, exposure to ERβ agonists showed a significant proliferation in ERα+, ERα- and ERβ+ cells. TAS activity was more pronounced and its anti-estrogen activity may involve ERβ in addition to ERα. [Table: see text]