tbuckley/cabot-search huggingface dataset:
Predictors of progression of bone metastases in breast cancer patients
Authors: W. El Ayass, S. Sereika, G. Van Londen, A. Brufsky
Journal: Journal of Clinical Oncology (2009)

e12011 Background: Breast cancer is mostly diagnosed in elderly women aged &gt;= 65 years and they constitute about 41% of all newly diagnosed cases. Bone metastases is a very common event in these patients especially those with estrogen receptor positive subtypes.Our aim is to identify factors that may be associated with progression of bone metastases in breast bancer (BC) patients with bone metastases only. Methods: Retrospective review of medical records of 50 females with breast cancer with only bone metastases evaluated at Magee Womens Hospital in Pittsburgh, Pennsyvlania, between June 1998 and September 2007. Patients’ progression of their bone disease was followed based on serial bone scans. Candidate predictors considered included: age at breast cancer diagnosis (as a continuous variable and dichotomized at 60 years), age at metastatic BC diagnosis (as a continuous variable and dichotomized at 60 years), time elapsed between breast cancer diagnosis, and metastatic BC diagnosis, ER status, PR status, ER/PR status, HER-2 status, use of radiation, type of bisphosphonate used (since all but two patients had this: aredia use, zometa use), type of disease (IDC, ILC), and stage of disease (I, II, III, IV). Marginal modeling using generalized estimating equations assuming a binomial error distribution was used considering potential candidate predictor variables univariately and then multivariately to identify predictors of progression of bone metastases at a significance level of 0.05. Results: Based on the univariate analysis, age at BC diagnosis (p = 0.03), age at metastatic BC diagnosis (p = 0.03), and being ER+ or PR+ (p = 0.04) were positively predictive of progression, with the latter two being also jointly significant in multivariate analysis. As anticipated, treatment with bisphosphonates and radiation therapy were found to have a protective role against progression. Conclusion: We found that age as a continuous variable and ER/PR + were positive predictors of progression of bone metastases in BC patients. These findings suggest an increased need of individualized treatment especially in elderly to prevent morbidity and lower cost. No significant financial relationships to disclose.
Stage-specific survival of patients with uterine leiomyosarcoma: A comparison of FIGO and AJCC staging system
Authors: O. Zivanovic, A. Iasonos, M. M. Leitao, Q. Zhou, R. A. Soslow, M. M. Juretzka, D. S. Chi, M. F. Brennan, M. L. Hensley
Journal: Journal of Clinical Oncology (2008)

5554 Background: Uterine Leiomyosarcoma (LMS) is staged by the modified International Federation of Gynecology and Obstetrics (FIGO) staging system for uterine cancer. We aimed to determine whether the American Joint Committee on Cancer (AJCC) Soft Tissue Sarcoma (STS) Staging System is more predictive of overall-survival (OS). Methods: We analyzed all patients (pts) with uterine LMS who presented at our institution from 1975 to 2005. The pts were staged retrospectively, according to the modification of the FIGO staging system for uterine cancer and the 6th edition of the AJCC STS staging system. OS estimates were determined using Kaplan-Meier method. The predictive accuracy of the two staging systems was compared using concordance estimation. Results: 220 pts had sufficient clinical and pathologic information for staging under both systems. 136 pts were upstaged in the AJCC staging system, whereas only 2 pts were down-staged. 126 patients were classified as FIGO Stage I. Of these, 25 patients were upstaged to AJCC Stage II and 84 to AJCC Stage III. Of 10 FIGO Stage II pts, 9 were AJCC Stage III. Of 33 FIGO Stage III pts 18 were upstaged to AJCC Stage IV and 2 were down-staged to AJCC stages I (low grade LMS) and II (<5cm) respectively. The median follow-up time for the surviving pts was 5.4 years (range: 0.6 to 21.8 years). Stage-specific OS rates for Stage I pts differed substantially between FIGO and AJCC (Table). In both systems there was prognostic overlap between Stages II and III. Thus, despite the marked stage-specific differences in 5-year OS rates for Stage I, the systems had similar concordance indices (0.64 for AJCC; 0.62 for FIGO). Conclusions: Estimates of stage-specific OS for uterine LMS were altered substantially when using AJCC v. FIGO. Adjuvant treatment strategies should be tested in patients at substantial risk for death. Neither FIGO nor AJCC is ideal for identifying such patients suggesting a need for a uterine LMS-specific staging system to better target pts for trials of adjuvant therapies. 5-year overall survival rate Stage FIGO AJCC I 58% (n=126) 94% (n=18) II 43% (n=10) 51% (n=27) III 36% (n=33) 51% (n=106) IV 16% (n=51) 19% (n=69) No significant financial relationships to disclose.
Isolated limb perfusion with high-dose ifosfamide in the treatment of locally advanced sarcoma. A pilot study
Authors: H. Martínez-Saíd, P. Alejandro, M. Cuellar, G. Rico, C. Lopez-Graniel, J.-L. Aguilar-Ponce, P. Cabrera, J. de la Garza
Journal: Journal of Clinical Oncology (2005)

9053 Background: Recent studies have evaluated the role of isolated limb perfusion (ILP) and hyperthermia in the management of extremity sarcoma. The agents most commonly employed for ILP have been melphalan and Tumor Necrosis Factor that increase significantly the response rate. We present the initial experience with ifosfamide in regional therapy. Methods: We conducted a prospective program of ILP and include five patients with histologically proved soft tissue and osseus sarcoma. All patients included had big tumors with no other option than amputation. All perfusions were done with ifosfamide (78 gr/m2 of perfunded limb area) and mild hyperthermia (39–40°C). The leakage monitoring was performed with Tc99 radiolabelled erythrocytes with a hand held gammaprobe. The clinical, pathologic and overall response rate was recorded. Results: There were five patients (2 women, 3 men) with a median age of 41 years. The median size was 19 cm. The level of perfusion was brachial (2) for the tumors located in the arm, iliac for the tumor located in the thigh and femoral for the tumor located in the knee. The clinical response rate was assessed with MRI, CT and Doppler ultrasound. The clinical response rate (CRR) was partial in three, for an overall CRR of 75%. The median leakage was 5% (0–6%). Regional toxicity was recorded according to Wieberdink scale; all the patients develop erithema and mild edema of the extremities (Wieberdink II). No late toxicity was recorded. There was transient neuropathy in the cases with clinical and pathologic response. The resection of residual tumor was done at two and three weeks after perfusion. The percentage of necrosis was recorded (Case 1:95%, Case 2: 10%, Case 3: 70%, Case 4: 70%). The patient with osseous sarcoma had a 95% of necrosis. A limb sparing procedure was successfully done in three cases. Adjuvant radiation therapy was included in all soft tissue cases, even with near complete pathologic response. With a median follow up of 8 months (2–16 months) three patients are alive, with no evidence of disease. Conclusions: Isolated Limb Perfusion with high dose ifosfamide and mild hyperthermia is efficient therapy for locally advanced soft tissue sarcoma. No significant financial relationships to disclose.
A challenging case of multiple splenic and pancreatic lesions in a patient with Crohn's disease
Authors: G Boschetti, S Assaad, B Balme, S Boyer, B Flourié, S Nancey
Journal: Gut (2015)

A 40-year-old woman with a history of ileocolonic Crohn's disease treated with oral mesalamine presented with fever and diffuse abdominal pain without diarrhoea. Laboratory tests were notable only for increased serum C-reactive protein (CRP) (46 mg/L) and leucocytosis (10 100 cells/μL) with neutrophilia (8700 cells/μL). Abdominal CT revealed multiple mesenteric lymph nodes (MLNs) without evidence of thickening of the bowel wall or complications such as stricture, fistula or abscess. Laparoscopic biopsy samples of some MLNs were performed; their histopathological analysis revealed a suppurative lymphadenitis, with a strong infiltration by neutrophils, oedema and tissue necrosis without granuloma or identification of any micro-organisms, including alcohol acid-resistant bacilli (AARB). Three …
Effect of pelvic exenteration type and vaginal reconstruction on quality of life.
Authors: Y. Rezk, F. Dao, K. Hurley, J. Carter, B. Bochner, J. Aubey, A. Caceres, N. Abu-Rustum, R. R. Barakat, D. Chi
Journal: Journal of Clinical Oncology (2010)

e19604 Background: This prospective study comprehensively examined quality of life (QOL) after pelvic exenteration (PE). The current analysis evaluates theeffect of PE type and vaginal reconstruction on QOL. Methods: 24 women enrolled on study since 2005, with > 6 months (m) of follow up. Median age was 57 yrs (28-78). Study battery (EORTC-QLQ-30, EORTC-CR38, BFI, BPI, IADL, CES-D, IES-R) was administered before and 6 m after PE. Additional 5-point Likert-scale questions supplemented these instruments. Partial PE (PPE; n=9)/total PE (TPE; n=15) and vaginal reconstruction (recon; n=10)/non-reconstruction (non-recon; n=14) groups were compared (Student t test). Results: QOL was comparable for all groups at baseline. At 6 m, overall QOL, ability to carry out daily activities, pain, fatigue, physical, emotional and social functions were comparable for PPE/TPE (t=1.29, t=1.13, t=0.88, t=−1.46, t=0.95, t=0.46, t=0.75, p's=NS; respectively) and the recon/non-recon (t=− 0.20, t=−1.83, t=−0.26, t=0.17, t=−1.64, t=0.37, t=−0.29, p's=NS; respectively) groups. No group differences were found for sexual function between PPE/TPE groups (t=−0.60, p=NS), but PPE pts reported better body image (t=2.19, p<0.039; 95% CI 1.38 to 48.49), the majority (89%) reporting moderate to extreme comfort with their bodily changes and adapting sooner than or as expected (versus 67% and 53% for TPE pts, respectively). Satisfaction with recovery time was also more common in the PPE group, with all pts being moderately to extremely satisfied versus 73% for TPE pts. For the recon/non-recon groups, body image was comparable (t=0.27, p=NS). However, stress-related ideation was more common (t=−2.16, p<0.041; 95% CI −1.10 to −0.02), possibly due to younger age and/or significantly better sexual function (t=−2.78, p<0.011; 95% CI −35.74 to −5.21) in the recon group. Conclusions: QOL was comparable regardless of PE type or vaginal reconstruction. However, PPE pts reported better adjustment and body image than TPE patients at 6 m. Longer follow up can determine if this domain is finally restored in TPE pts. Vaginal reconstruction had a positive impact on sexuality and ought to be considered when feasible. This information can be used to enhance patient counseling/support. No significant financial relationships to disclose.
For a better, safer and healthier tomorrow - Our commitment to research in emerging infectious diseases at the University of Hong Kong
Authors: P. C.Y. Woo, S. S.Y. Wong, K. H. Chan, Y. Guan, R. Y.T. Kao, K. Y. Yuen, S. K.P. Lau, J. S.M. Peiris, P. L. Ho, L. L.M. Poon, B. J. Zheng, W. C. Yam
Journal: Nature Medicine (2004)
Outcome Of Unrelated Umbilical Cord Blood Transplantation For Children With Osteopetrosis: An Eurocord and Inborn Errors Working Party (IEWP)-EBMT Study
Authors: Robert Chiesa, Annalisa Ruggeri, Marco Zecca, Franco Locatelli, Marta Gonzalez-Vincent, Victoria Bordon, Isaac Yaniv, Sarah Lawson, Xavier Poire, Giorgio Dini, Manuel Abecasis, Amal Al-Seraihy, Chantal Kenzey, Erick Xavier, Marc Bierings, Eliane Gluckman, Ansgar S Schulz, Andrew Gennery, Vanderson Rocha
Journal: Blood (2013)
The transcription factor BACH2 promotes tumor immunosuppression
Authors: Rahul Roychoudhuri, Robert L. Eil, David Clever, Christopher A. Klebanoff, Madhusudhanan Sukumar, Francis M. Grant, Zhiya Yu, Gautam Mehta, Hui Liu, Ping Jin, Yun Ji, Douglas C. Palmer, Jenny H. Pan, Anna Chichura, Joseph G. Crompton, Shashank J. Patel, David Stroncek, Ena Wang, Francesco M. Marincola, Klaus Okkenhaug, Luca Gattinoni, Nicholas P. Restifo
Journal: Journal of Clinical Investigation (2016)

The immune system has a powerful ability to recognize and kill cancer cells, but its function is often suppressed within tumors, preventing clearance of disease. Functionally diverse innate and adaptive cellular lineages either drive or constrain immune reactions within tumors. The transcription factor (TF) BACH2 regulates the differentiation of multiple innate and adaptive cellular lineages, but its role in controlling tumor immunity has not been elucidated. Here, we demonstrate that BACH2 is required to establish immunosuppression within tumors. Tumor growth was markedly impaired in Bach2-deficient mice and coincided with intratumoral activation of both innate and adaptive immunity. However, augmented tumor clearance in the absence of Bach2 was dependent upon the adaptive immune system. Analysis of tumor-infiltrating lymphocytes from Bach2-deficient mice revealed high frequencies of rapidly proliferating effector CD4+ and CD8+ T cells that expressed the inflammatory cytokine IFN-γ. Effector T cell activation coincided with a reduction in the frequency of intratumoral Foxp3+ Tregs. Mechanistically, BACH2 promoted tumor immunosuppression through Treg-mediated inhibition of intratumoral CD8+ T cells and IFN-γ. These findings demonstrate that BACH2 is a key component of the molecular program of tumor immunosuppression and identify therapeutic targets for the reversal of immunosuppression in cancer.
15-Deoxy-Δ12,14-prostaglandin J2 stabilizes p53 protein in human breast cancer (MCF-7) cells
Authors: Do-Hee Kim, Young-Joon Surh
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

754 

Cyclopentenone prostaglandins (cyPGs) exert cellular functions by multiple mechanisms. 15-Deoxy-Δ12,14-prostaglandin J2(15d-PGJ2), as a representative cyPG, has a wide range of pharmacological effects such as anti-tumor activity, inhibition of cell cycle progression and induction of heat shock protein expression. The distinct biological activity of 15d-PGJ2 has been attributed to the electrophilic α,β-unsaturated carbonyl moiety of its cyclopentenone ring which interacts preferentially with nucleophiles, such as thiol groups present in cysteine residues of diverse cellular proteins. In the present study, we found that 15d-PGJ2 (30 μM) inhibited proliferation of MCF-7 human breast cancer cells and induced up-regulation of the tumor suppressor gene product p53 which was accumulated in both cytosolic and nuclear fractions. Under the same experimental conditions, however, 15d-PGJ2 neither increased the mRNA level nor DNA binding of p53. We investigated the molecular mechanisms responsible for the 15d-PGJ2-mediated accumulation of p53. The stability of p53 protein has been known to be regulated via its phosphorylation mediated by JNK. In line with this notion, the expression of p53 protein was accompanied by up-regulation of the c-Jun through the JNK pathway. In addition, murine double-minute 2 (MDM2) was also transiently up-regulated in parallel with p53 accumulation. Failure of continuous MDM2 expression can cause the stabilization of p53 protein by blocking its degradation. It was anticipated that the electrophilic carbon center of 15d-PGJ2might be critical for the retardation of p53 degradation. We hypothesize that 15d-PGJ2-induced covalent modification of p53 could prevent its ubiquitination and subsequent proteolysis mediated by MDM2. In support of this assumption, MCF-7 cells treated with 9,10-dihydro-15-deoxy-Δ12,14-PGJ2 that lacks the electrophilic α,β-unsaturated functionality failed to accumulate p53 protein product. Moreover, we observed up-regulation of p21, which is a p53-responsive gene, in the MCF-7 cells treated with 15d-PGJ2 but not with its saturated 9,10-dihydro homolog. In summary, 15d-PGJ2 could stabilize p53 by post-translational modification in MCF-7 cells.
Safety and efficacy of percutaneous radio-frequency ablation (RFA) in patients (pts) with metastatic gastrointestinal stromal tumor (GIST) with clonal evolution of lesions refractory to imatinib mesylate (IM)
Authors: P. Dileo, R. Randhawa, E. Vansonnenberg, S. Shankar, J. Desai, J. A. Morgan, K. Tuncali, A. Van Den Abbeele, S. G. Silverman, G. D. Demetri
Journal: Journal of Clinical Oncology (2004)

9024 Background: IM is a highly effective treatment for metastatic/unresectable GIST. Although pts may exhibit durable systemic disease control, with time clonal evolution of lesions refractory to IM emerge and require alternative treatment approaches. We have evaluated the role of percutaneous RFA in this subset of pts with single or oligoclonal progressing GIST lesions who are in good performance status. Methods: Pts with limited sites of GIST progressing despite continuation of IM were treated with CT-guided RFA. All pts had staging with CT/MRI as well as functional imaging with 18FDG PET scans, both before and after RFA. Biopsy of the target lesions was performed before RFA. Results: Nine pts treated with imatinib for a median of 25 months (m) (range 18–36 m) underwent RFA for single or limited site(s) of progressing disease. Sites of progression: 8/9 pts with liver metastases, 1/9 with soft tissue disease. 5/9 of these pts developed a new nodule within a pre-existing GIST lesion, the remaining 4/9 had anatomic progression of pre-existing sites or developed a new site of disease. Pts undergoing the procedure were asymptomatic and had a good baseline performance status (ECOG 0–1). Progressing lesions were not 18FDG-avid by PET scanning in 5 pts. No pt developed early or late complications from the procedure. With median follow-up of 4.2 m (range 1–11 m), all pts had their lesions completely ablated. 5/9 pts progressed systemically and had an increase in their imatinib dosing (from 400 or 600mg/d to 800mg/d), resulting in disease control for an additional 1–6 m (median 3.5 m). 4 pts remain stable on continued treatment with imatinib (median follow-up 5.8 m). Conclusion: In this small cohort, percutaneous RFA appears to be a safe and effective treatment for localized sites of progression. This procedure helps to manage limited IM-resistant GIST. Continuation of IM to control systemic sites of IM-sensitive GIST despite emergence of limited clonal resistance can be justified on the basis of this exploratory work. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis; Pfizer Novartis; Pfizer
Is Anastrozole Superior to Tamoxifen as First-Line Therapy for Advanced Breast Cancer?: In Reply
Authors: J. M. Nabholtz, J. Bonneterre, A. Buzdar, J. F.R. Robertson, B. Thürlimann, M. Steinberg, A. Webster, M. von Euler
Journal: Journal of Clinical Oncology (2001)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.9.2580 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11331346 Is Anastrozole Superior to Tamoxifen as First-Line Therapy for Advanced Breast Cancer?: In Reply J. M. NabholtzxJ. M. NabholtzSearch for articles by this author , J. BonneterrexJ. BonneterreSearch for articles by this author , A. BuzdarxA. BuzdarSearch for articles by this author , J. F.R. RobertsonxJ. F.R. RobertsonSearch for articles by this author , B. ThürlimannxB. ThürlimannSearch for articles by this author , M. SteinbergxM. SteinbergSearch for articles by this author , A. WebsterxA. WebsterSearch for articles by this author , M. von EulerxM. von EulerSearch for articles by this author Show More University of California at Los Angeles, Los Angeles, CACenter Oscar Lambret, Lille, FranceM.D. Anderson Cancer Center, Houston, TXCity Hospital, Nottingham, United KingdomMedizinische Klinic C Kantonsspital, St Gallen, SwitzerlandAstraZeneca, Wilmington, DEAstraZeneca, Alderly Park, Cheshire, United Kingdom https://doi.org/10.1200/JCO.2001.19.9.2580 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
Survey of U.S. lung cancer media coverage between 1999/2000 and 2003/2004
Authors: D. Blum, W. Boerckel
Journal: Journal of Clinical Oncology (2005)

7223 Background: In preparation for the launch of a lung cancer awareness campaign in 2000, a survey was conducted to assess media coverage for the four major cancers (breast, prostate, lung, colorectal). Results found the majority of articles addressed breast cancer, while lung cancer (the leading cancer killer) was underreported, and articles carried negative messages, were unsympathetic to patients, and focused on tobacco-related issues. With a perceived increase in lung cancer research and celebrity-supported education initiatives, a 2004 follow-up was commissioned to determine if lung cancer coverage has increased and become more positive. Methods: Research firm Carma International conducted two parallel online searches (Aug. 1999 - July 2000 and Aug. 2003 - July 2004) to retrieve systematic random samples of 600 breast, prostate, lung and colorectal stories and transcripts from national newspapers, newswires, consumer magazines, newsweeklies, and broadcast news. Content analysis included symptoms, prevention, detection, treatment, survival, research, personal accounts, events and tobacco/smoking. Coverage was analyzed by volume, story type, topics, awareness events and celebrity outreach. Results: Findings showed lung cancer coverage increased 10% (105 to 116), while breast cancer coverage decreased 10% (368 to 333). Lung cancer coverage was more positive; treatment and research references increased from 21 to 29 and 22 to 32 respectively, while tobacco/smoking references decreased from 48 to 36. Patient-focused stories addressing clinical trials and psychosocial issues increased from 4 to 18. Celebrity-focused lung cancer articles increased from 2 to 10, while celebrity breast cancer articles decreased from 35 to 10. Conclusions: There are more lung cancer articles conveying positive messages and greater celebrity involvement than at the start of the campaign. Contributing factors are likely related to celebrity involvement and coverage of new treatments. Given lung cancer’s toll, education and awareness campaigns must continue to drive coverage. A follow-up survey should be conducted to determine if this increase in positive coverage translates into less stigma and blame toward lung cancer patients. No significant financial relationships to disclose.