tbuckley/cabot-search huggingface dataset:
A synthetic peptide-based erythropoiesis stimulating agent (ESA) (Hematide) demonstrates dose dependent activity and is well tolerated in a phase 1 single dose, dose escalating study in normal healthy volunteers (NHV)
Authors: R. B. Stead, J. Lambert, D. Wessels, J. Iwashita, K. Leuther, K. Woodburn, P. Schatz, A.-M. Duliege
Journal: Journal of Clinical Oncology (2005)

8180 Background: Hematide is an innovative, synthetic, pegylated, peptidic ESA that binds to and activates the erythropoietin (EPO) receptor. Although its amino acid sequence is unrelated to that of EPO, Hematide demonstrates in vitro and in vivo activities comparable to EPO and an extended serum half life in animal studies. This may allow less frequent dosing in patients with chronic anemia relative to EPO. Methods: A randomized double-blind placebo controlled dose escalation study was conducted to assess safety, PK and PD of Hematide administered as a single IV infusion to male NHV. Up to 7 cohorts of 7 subjects each (5 on Hematide and 2 on placebo) were planned with doses escalated unless or until stopping rules were met. Results: Three dose cohorts have been completed involving 21 NHV. As of this date, the study remains blinded and we assume increases in reticulocytes and hemoglobin (Hb) are due to Hematide. Injections were well tolerated with report of only a few Grade 1 adverse events and no pattern across cohorts. Reticulocyte increases were dose proportional; average reticulocyte peak concentrations (+/- SE) were 148 (+/- 19); 186 +/- (20); 230 (+/- 22) 109/L among the NHV with a reticulocyte response in Cohort 1 (n=4), Cohort 2 (n=5), and Cohort 3 (n=5) respectively, compared to 59 (+/- 5) 109/L among the 7 (pooled) non-responding subjects. In Cohort 3, an increase in Hb was seen in 5 subjects. The mean difference in changes from baseline Hb between these 5 responding and the 2 non-responding subjects was 1.0 g/dL at day 9 (p = 0.014) and remained detectable as of Day 35. Unblinded results, including PK data, will be presented. Conclusions: A single IV injection of Hematide administered to NHV was well tolerated and demonstrated potent dose dependent erythropoietic activity. These data will be used to plan Phase 2 studies of Hematide in patients with anemia related to cancer and renal failure. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Affymax Affymax Affymax, Amgen
Gemcitabine (G) and irinotecan (CPT-11) as first-line therapy for carcinoma (ca) of unknown primary (CUP): An NCCTG phase II trial
Authors: S. G. Holtan, N. R. Foster, C. E. Erlichman, M. Aubry, M. M. Ames, S. Safgren, P. D. Steen, R. F. Morton, D. Graham, M. P. Goetz
Journal: Journal of Clinical Oncology (2008)

13525 Background: The combination of G and CPT-11 was reported as a promising regimen for CUP in the 2nd line setting (Hainsworth, Cancer 2005). We sought to determine the activity and toxicity of weekly G and CPT-11 as first-line therapy for CUP, and to assess the relationship between UGT1A1*28 genotype and toxicity. Methods: Pts with untreated metastatic ca, ECOG PS 0–2, and good organ function were eligible. Sufficient tumor tissue was required for central review to exclude lung, melanoma, hematologic, and neuroendocrine ca. Additionally, the following pts were ineligible: women with ca restricted to axillary lymph nodes (LN) or with ca limited to peritoneum; men with mediastinal or retroperitoneal tumors and positive tumor or serum germ cell markers; men with blastic bony metastases or elevated PSA; pts with ca involving only one site; and pts with squamous ca limited to LN. Treatment was G 1,000 mg/m2 and CPT- 11 75 mg/m2 weekly×four (6 week cycle, Cohort I) with an interim analysis to assess toxicity and the role of UGT1A1*28 genotype on toxicity. Following the observation of excessive Cohort I toxicity, the schedule was modified: G 750 mg/m2 and CPT- 11 75 mg/m2 weekly x3 of a 4 week cycle for Cohort II. Results: 31 pts were enrolled with a median age of 63 (range: 38 –94). A median of 2 cycles was administered (range: 1–14). Toxicity and efficacy are listed in Table 1. Cohort I pts experienced substantial hematologic (H) and non-H adverse events (AE), unrelated to UGT1A1*28 genotype (p=0.74 and 0.92, respectively). Cohort II pts had significantly less toxicity (Table 1). Both cohorts demonstrated lack of sufficient activity for continuation to the 2nd stage. Conclusions: The combination of G and CPT-11 is not active in CUP. A multidisciplinary clinical and pathologic approach to diagnose CUP identifies patients with inherent resistance to combination chemotherapy and a poor prognosis. New therapeutic approaches are needed. Trial was supported by Cancer Center grant CA15083 and NCCTG grant CA25224. Efficacy and Cycle 1 AE summary Cohort Dose (mg/m2/day) Grade 4+ AE* Grade 3+ Heme AE** TTP (95% CI) TTF (range) RR I CPT-11 75, Gem 1,000 29% 50% 3.7 (2.8 –7.8) 2.3 (0.2 –19.7) 1/11 (9%) II CPT-11 75, Gem 750 6% 6% 3.6 (1.9 –13.8) 1.8 (0.9 –7.7) 2/15 (13%) AE, adverse events; TTP, median time to progression in months; TTF, median time to treatment failure in months; RR, confirmed response rate (all PR’s), *p =0.15; **p=0.01. No significant financial relationships to disclose.
Radiosurgery for pituitary adenomas: Evaluation of its efficay and safety
Authors: J. V. Salvajoli Sr., D. G. Castro, S. A. Cecílio, M. M. Canteras
Journal: Journal of Clinical Oncology (2006)

11515 Background: Pituitary adenomas account for approximately 15% of all primary brain tumors. Multimodality treatment is often necessary and options include medical management, microsurgery, radiotherapy and radiosurgery (RS). Recently, RS has gained acceptance as a complementary treatment since it has been associated with a shorter latency for its effects and lesser morbidity than that of radiotherapy. The objective of this study was to assess the effects of RS on the radiological and hormonal control and its toxicity in the treatment of pituitary adenomas. Methods: It was done a retrospective analysis of the first 26 consecutive patients with pituitary adenomas treated with RS at our institution between 1999 and 2004. RS was delivered with a multiheaded cobalt unit (Gamma Knife). The median radiation dose was 20 Gy defined to the 50% isodose line. Almost 20% of tumors were non-secretory. The remaining were prolactinomas (31%), adrenocorticotropic hormone-secreting (34%) and growth hormone-secreting tumors (15%). Hormonal control was defined as hormonal response (decline of more than 50% from the pre-RS levels) and hormonal normalization. Radiological control was defined as stasis and shrinkage of the tumor. Hypopituitarism and visual deficit were the morbidity outcomes. Hypopituitarism was defined as the initiation of any hormone replacement therapy and visual deficit as loss of visual acuity or visual field after RS. Results: The median follow-up was 40,8 months.Tumor growth was controlled in 96% of the cases and tumor shrinkage ocurred in 8% of the cases. Hormonal control was observed in 14 of 20 (70%) and hormonal normalization in 7 of 20 (35%) patients after RS, with a median latency period of 28,2 months. The 3-year actuarial rate of hormonal control and normalization were 51% and 47,6%, respectively, and the 5-year actuarial rate were 74% and 68,6%, respectively. There were no patients with visual deficit or hypopituitarism after RS. Conclusions: RS is an effective and safe therapeutic option in the management of selected patients with pituitary adenomas. The short latency of the radiation response, the highly acceptable radiological and hormonal control and absence of complications at this early follow-up are consistent with literature. No significant financial relationships to disclose.
The relation between body mass index, comorbidity, choice of surgery, and prognostic factors in early breast cancer: Data from a nation-wide Danish cohort
Authors: A. R. Jensen, S. Christensen, R. Zachariae, S. Moller, A. B. Jensen
Journal: Journal of Clinical Oncology (2008)

11110 Background: Available evidence suggests that overweight is associated with incidence and prognosis of breast cancer. We explore the associations between Body Mass Index (BMI), prognostic factors and choice of surgery. Methods: The study included 4917 women aged 18–70 yrs. diagnosed with primary loco-regional breast cancer from October 2001 to March 2004. Sixty-eight percent (3343) returned a questionnaire including data on height and weight. Comorbidity was assessed using Charlson Comorbidity Index (CCI). The Danish Breast Cancer Cooperative Group provided data on surgery and prognostic factors. Differences in treatment associated with (BMI) and CCI- score were analysed with χ2-tests. Correlations between BMI, CCI, age, tobacco, alcohol, and prognostic factors were analyzed using Spearman‘s ρ. Results: Twenty-six percent had BMI >25 and 8% had BMI >30. Twelve percent had CCI-score>0, the majority (80%) having one comorbid condition. Prevalence of comorbidity increased significantly with both BMI and age (p<0.001). There was a positive association between CCI-score and mastectomy (p<0.001), whereas sentinel-lymphnode procedures decreased with increasing CCI-score (p<0.001). No associations were found between CCI-score and tumour size, grade, oestrogen-receptor status, number of removed or metastatic lymphnodes. Increasing BMI was positively correlated with age and use of alcohol or tobacco. The incidence of sentinel-lymphnode procedures decreased with BMI above 25, whereas the number of lymphnodes removed increased with higher BMI. BMI was not associated with the chance of mastectomy. Higher BMI was significantly correlated to 1)increasing tumour size, from median 14 mm in patients with BMI<18.5 to 22 mm for BMI≥30, 2)increasing number of positive lymphnodes, 3)stage and 4)grade, but not oestrogen-receptor status. Conclusions: The study suggest that higher BMI is associated with increased comobidity and negative prognostic factors. Patients with overweight had more extensive axillary surgery and more positive lymphnodes. Comorbidity did not influence prognostic factors. A correlation between surgery and comorbidity was found. However, these differences are not expected to affect outcome. No significant financial relationships to disclose.
Expression of 4-Integrin Defines the Earliest Precursor of Hematopoietic Cell Lineage Diverged From Endothelial Cells
Authors: Minetaro Ogawa, Masami Kizumoto, Satomi Nishikawa, Tetsuhiro Fujimoto, Hiroaki Kodama, Shin-Ichi Nishikawa
Journal: Blood (1999)
Evolution of messenger RNA structure and regulation in the genus Mus: the androgen-inducible RP2 mRNAs.
Authors: A Chaudhuri, K W Barbour, F G Berger
Journal: Molecular Biology and Evolution (1991)

The RP2 gene is one of several genes that are regulated by androgens in the mouse kidney. Previous studies have demonstrated that androgen inducibility of RP2 transcription varies among species within the genus Mus, indicating extensive evolutionary modification of the participating regulatory elements. Thus, while a five-fold induction of transcription occurs in M. domesticus, none is detectable in M. hortulanus or M. caroli. In the present paper, we have sequenced cDNAs representing the RP2 mRNAs of M. caroli and M. saxicola and have compared them with each other and with M. domesticus. Several findings from the sequence comparisons indicate that the encoded 41-kD polypeptide is physiologically functional. First, divergence within noncoding regions of the mRNAs exceeds that within coding regions. Second, the 357-codon open reading frame has been maintained among the species, with approximately 90% of the amino acid replacements being conservative. Finally, substitution rates at synonymous sites within the coding regions are from twofold to threefold greater than those at nonsynonymous sites. The genetic elements responsible for variations in RP2 inducibility among species were studied by cis/trans analyses of mice heterozygous for RP2 alleles, using a primer extension assay to measure expression of species-specific mRNAs. The results show that the absence of transcriptional induction in M. hortulanus is due to a cis-acting genetic element, while that in M. caroli is due to a trans-acting element. Thus, the androgen-resistant RP2 phenotypes of these two species derive from distinct genetic events.
Aster 70S Unicancer Phase III Trial : Adjuvant Treatment for Women Over 70 with Luminal Breast Cancer
Authors: C. Dubot, Y. Tazi, E. Bourbouloux, S. Kirscher, O. Rigal, S. Abadie-Lacourtoisie, J. Ferrero, H. Curé, E. Blot, D. Allouache, G. Romieu, P.H. Cottu, E. Malaurie, C. Terret, M. Triki Lacroix, F. Rollot, H. Peyro Saint Paul, C. Orsini, F. Bonnetain, E. Brain
Journal: Annals of Oncology (2014)
Yolk Sac Carcinoma Grown From Rat Egg Cylinders 2
Authors: Ivan Damjanov, Stewart Sell
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Yolk Sac Carcinoma Grown From Rat Egg Cylinders Get access Ivan Damjanov, Ivan Damjanov Search for other works by this author on: Oxford Academic PubMed Google Scholar Stewart Sell Stewart Sell Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 5, May 1977, Pages 1523–1525, https://doi.org/10.1093/jnci/58.5.1523 Published: 01 May 1977 Article history Received: 20 August 1976 Accepted: 03 November 1976 Published: 01 May 1977
Does VEGF facilitate local tumor growth and spread into the abdominal cavity by suppressing endothelial cell adhesion, thus increasing vascular peritoneal permeability followed by ascites production in ovarian cancer?
Authors: Inga Bekes, Thomas W. P. Friedl, Tanja Köhler, Volker Möbus, Wolfgang Janni, Achim Wöckel, Christine Wulff
Journal: Molecular Cancer (2016)

Ovarian cancer is mostly associated with pathologically regulated permeability of peritoneal vessels, leading to ascites. Here, we investigated the molecular regulation of endothelial permeability by the vascular endothelial growth factor (VEGF) and both tight and adherens junction proteins (VE-cadherin and claudin 5) with regards to the tumor biology of different ovarian cancer types.Serum and ascites samples before and after surgery, as well as peritoneal biopsies of 68 ovarian cancer patients and 20 healthy controls were collected. In serum and ascites VEGF protein was measured by ELISA. In peritoneal biopsies co-localization of VE-cadherin and claudin 5 was investigated using immunohistochemical dual staining. In addition, the gene expression of VE-cadherin and claudin 5 was quantified by Real-time PCR. Differences in VEGF levels, VE-cadherin and claudin 5 gene expression were analyzed in relation to various tumor characteristics (tumor stage, grading, histological subtypes, resection status after surgery) and then compared to controls. Furthermore, human primary ovarian cancer cells were co-cultured with human umbilical vein endothelial cells (HUVEC) and changes in VE-cadherin and claudin 5 were investigated after VEGF inhibition.VEGF was significantly increased in tumor patients in comparison to controls and accumulates in ascites. The highest VEGF levels were found in patients diagnosed with advanced tumor stages, with tumors of poor differentiation, or in the group of solid / cystic-solid tumors. Patients with residual tumor after operation showed significantly higher levels of VEGF both before and after surgery as compared to tumor-free resected patients. Results of an immunohistochemical double-staining experiment indicated co-localization of VE-cadherin and claudin 5 in the peritoneal vasculature. Compared to controls, expression of VE-cadherin and claudin 5 was significantly suppressed in peritoneal vessels of tumor patients, but there were no significant differences regarding VE-cadherin and claudin 5 expression in relation to different tumor characteristics. A significant positive correlation was found between VE-cadherin and claudin 5 expression. VEGF inhibition in vitro was associated with significant increase in VE-cadherin and claudin 5.Our results indicate that increased peritoneal permeability in ovarian cancer is due to down-regulation of adhesion proteins via tumor derived VEGF. Advanced ovarian cancer with aggressive tumor biology may be associated with early dysregulation of vascular permeability leading to ascites. These patients may benefit from therapeutic VEGF inhibition.
Risk of invasive cervical cancer after atypical glandular cells in cervical screening: nationwide cohort study
Authors: Jiangrong Wang, Bengt Andrae, Karin Sundström, Peter Ström, Alexander Ploner, K Miriam Elfström, Lisen Arnheim-Dahlström, Joakim Dillner, Pär Sparén
Journal: BMJ (2016)

<b>Objectives</b>&nbsp;To investigate the risks of invasive cervical cancer after detection of atypical glandular cells (AGC) during cervical screening. <b>Design</b>&nbsp;Nationwide population based cohort study. <b>Setting</b>&nbsp;Cancer and population registries in Sweden. <b>Participants</b>&nbsp;3 054 328 women living in Sweden at any time between 1 January 1980 and 1 July 2011 who had any record of cervical cytological testing at ages 23-59. Of these, 2 899 968 women had normal cytology results at the first screening record. The first recorded abnormal result was atypical glandular cells (AGC) in 14 625, high grade squamous intraepithelial lesion (HSIL) in 65 633, and low grade squamous intraepithelial lesions (LSIL) in 244 168. <b>Main outcome measures</b>&nbsp;Cumulative incidence of invasive cervical cancer over 15.5 years; proportion of invasive cervical cancer within six months of abnormality (prevalence); crude incidence rates for invasive cervical cancer over 0.5-15.5 years of follow-up; incidence rate ratios compared with women with normal cytology, estimated with Poisson regression adjusted for age and stratified by histopathology of cancer; distribution of clinical assessment within six months after the abnormality. <b>Results</b>&nbsp;The prevalence of cervical cancer was 1.4% for women with AGC, which was lower than for women with HSIL (2.5%) but higher than for women with LSIL (0.2%); adenocarcinoma accounted for 73.2% of the prevalent cases associated with AGC. The incidence rate of invasive cervical cancer after AGC was significantly higher than for women with normal results on cytology for up to 15.5 years and higher than HSIL and LSIL for up to 6.5 years. The incidence rate of adenocarcinoma was 61 times higher than for women with normal results on cytology in the first screening round after AGC, and remained nine times higher for up to 15.5 years. Incidence and prevalence of invasive cervical cancer was highest when AGC was found at ages 30-39. Only 54% of women with AGC underwent histology assessment within six months, much less than after HSIL (86%). Among women with histology assessment within six months, the incidence rate of cervical cancer after AGC was significantly higher than that after HSIL for up to 6.5 years. <b>Conclusions</b>&nbsp;AGC found at cervical screening is associated with a high and persistent risk of cervical cancer for up to 15 years, particularly for cervical adenocarcinoma and women with AGC at age 30-39. Compared with the reduction in risk of cancer seen after HSIL management, management of AGC seems to have been suboptimal in preventing cervical cancer. Research to optimise management is needed, and a more aggressive assessment strategy is warranted.
Mirza Basheer Baig
Authors: Samina Baig
Journal: BMJ (2015)

Mirza Basheer Baig was one of thousands of Indian doctors who answered the aspirational call in the 1950s and 60s to come and work for the NHS. Indeed, overseas doctors helped to maintain a smooth universal service. During a House of Lords debate in 1961, Lord Cohen of Birkenhead commented: “The whole of our hospital service would have collapsed had it not been for the enormous influx of junior …
临床证据（八）——肺癌
Authors: Alan, Neviue
Journal: BMJ (2002)

背景知识定义 肺癌或支气管癌是上皮细胞癌 ,起源于支气管表面上皮或支气管粘液腺体 (文后附表 )。发病率 /患病率 肺癌是导致男性和女性癌症患者死亡的主要原因。在美国每年大约有 1 0万男性和 8万女性患病。在英国每年约有 4万人患病。小细胞肺癌占肺癌总数的 2 0 %～ 2 5 % ,其余的是非小细胞肺癌 ,腺癌是非小细胞肺癌的主要类型1 。病因学 /危险因素 吸烟仍然是主要的可预防的危险因素 ,约 80 %～ 90 %的患者吸烟。预后 肺癌总的 5年生存率是 1 0 %～ 1 2 % 2 。诊断明确时 ,只有 1 0 %～ 1 5 %的肺癌患者无转移。即使给予这些患者根治性的外科手术治疗
The tyrosine kinase AXL sustains EMT and tumour-associated inflammation in triple-negative breast cancers
Authors: C. Raschioni, G. Bottai, B. Szekely, A. Losurdo, L. Di Tommaso, C. Tinterri, L. Paladini, J. Kulka, M. Roncalli, L. Santarpia
Journal: Annals of Oncology (2015)
Domiciliary non-invasive ventilation in patients 65 years or older. A case series study
Authors: María Antolina Gόmez Lόpez, María Josefa Díaz de Atauri Rodríguez de los Ríos, Salvador de la Torre Carazo, Jesús Muñoz Méndez, Beatriz Arias Arco, Trinidad Díaz Cambriles
Journal: European Respiratory Journal (2011)

Aim:  To describe the clinic characteristics of patients with domiciliary non-invasive ventilation (DNIV) in 65 years or older at BIPAP onset in a Sleep Disorders Unit (SDU).   Methods:  Transversal descriptive study of a case series between February 2000 and June 2010. Inclusion criteria: 1. Age ≥ 65 years at BIPAP onset. 2. Polisomnography or Polygraphy available prior BIPAP prescription.  Definitions: SAHS was considered when AHI ≥ 10 and severe SAHS if AHI ≥ 30; Obesity Hypoventilation Syndrome (OHS) was defined as a BMI ≥ 30 and PaCO 2  ≥ 45 mmHg at daytime; Excessive Daytime Somnolence (EDS) if Epworth Somnolence Scale (ESS) score ≥ 12.   Results:  82 out of 153 patients with DNIV met the inclusion criteria. 53 (65%) women and 29 (35%) men. Values expressed by mean ± standard deviation were: Age when starting treatment: 72±4; BMI: 37.54±6.9; neck circumference: 41.9±3.5 cm; ESS: 10.7±5.3; EDS: 37 (41%) patients; AHI: 31.7±22. SAHS was diagnosed in 75 (91.5%) patients and was severe in 36 (44%). BIPAP prescription was due to: OHS in 48 (59%) patients, combined pathology in 20 (24%) patients, neuromuscular disease in 9 (11%) and COPD in 5 (6%) patients.  BIPAP was initially prescribed in 38 (46%) patients, most of them with neuromuscular disease and combined pathology (p 0.017). Conversely, in 44 (54%) patients, most of them with OHS or COPD (p 0,017), it was prescribed CPAP at first and changed to BIPAP.   Conclusions:  Half of the patients with DNIV were ≥ 65 years old at the beginning of the treatment. All patients were obese and most of them, women. The most common cause of prescribing BIPAP was neuromuscular disease and the most common cause of change from CPAP to BIPAP was OHS.
Abstract 14678: Lower Serum Eicosapentaenoic Acid Predicts the Incidence of Paroxysmal Atrial Fibrillation During Hospital Stay in Patients With Acute Coronary Syndrome
Authors: Atsushi Sakamoto, Natsuko Hosoya, Toru Yoshizaki, Shigetaka Kageyama, Ryosuke Takeuchi, Koichiro Murata, Ryuzo Nawada, Tomoya Onodera, Akinori Takizawa, Masao Saotome, Hiroshi Satoh, Hideharu Hayashi
Journal: Circulation (2013)

Background: Emerging evidences have suggested the relationship between the lower serum omega-3 fatty acid fractions and the incidence of atrial fibrillation (A-fib). However, it is still elusive wh...
Leukemia Induced by 7 ,12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene in Germfree Rats&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Pollard, Morris, Kajima, Masahiro
Journal: JNCI Journal of the National Cancer Institute (1967)

Journal Article Leukemia Induced by 7 ,12-Dimethylbenz[a]anthracene in Germfree Rats Get access Morris Pollard, Morris Pollard Lobund Laboratory, University of Notre Dame, Notre Dame, lndiana 46556 Search for other works by this author on: Oxford Academic PubMed Google Scholar Masahiro Kajima Masahiro Kajima Lobund Laboratory, University of Notre Dame, Notre Dame, lndiana 46556 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 39, Issue 1, July 1967, Pages 135–141, https://doi.org/10.1093/jnci/39.1.135 Published: 01 July 1967 Article history Received: 17 January 1967 Published: 01 July 1967