tbuckley/cabot-search huggingface dataset:
Risk factors for late cytomegalovirus infection after allogeneic stem cell transplantation using HLA-matched sibling donor: Donor lymphocyte infusion and previous history of early CMV infection
Authors: D. H. Kim, J. H. Baek, J. G. Kim, S. K. Sohn, J. S. Suh, K. S. Lee, K. B. Lee
Journal: Journal of Clinical Oncology (2004)

6648 Background: An increased incidence of late cytomegalovirus (CMV) infection has been reported during the last decade since the introduction of ganciclovir (GCV) prophylaxis or GCV pre-emptive therapy. Given that a donor lymphocyte infusion (DLI) can induce more severe GVHD, this may predispose a patient to late CMV infection. Methods: Sixty-four patients (median age 36, M/F 38/26) underwent allogeneic stem cell transplantation (SCT) using a matched sibling donor with bone marrow (n=9) or peripheral blood stem cells (n=55). Results: The overall incidence of CMV infection, early, and late CMV infection was 46.9 (30/64), 42.2 (27/64), and 16.4% (9/55), respectively. Early CMV infection was treated with GCV pre-emptive therapy that produced a 92.6% success rate. Among the 20 patients who received 35 DLIs with a median of 1.31x108/Kg CD3+ cells, late CMV infection developed in 8 (42.1%) out of 19 evaluable cases with the median onset at 127 days post-transplant. The risk factors for late CMV infection in a logistic regression analysis included DLIs (p=0.001, HR 40.548, 95% CI [3.382, 486.094]) and a previous history of CMV infection (p=0.006, HR 40.548, 95% CI [3.382, 486.094]). Conclusions: In conclusion, late CMV infection was strongly associated with DLIs and a previous history of early CMV infection. Accordingly, extended surveillance of CMV antigenemia is recommended for patients receiving DLIs or who have a previous history of CMV infection. No significant financial relationships to disclose.
Importance of Innovations in Neonatal and Adolescent Health in Reaching the Sustainable Development Goals by 2030
Authors: Christopher R. Sudfeld, Wafaie W. Fawzi
Journal: JAMA Pediatrics (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
The p53/p21 Complex Regulates Cancer Cell Invasion and Apoptosis by Targeting Bcl-2 Family Proteins
Authors: Eun Mi Kim, Chan-Hun Jung, Jongdoo Kim, Sang-Gu Hwang, Jong Kuk Park, Hong-Duck Um
Journal: Cancer Research (2017)

Abstract The tumor suppressor p53 binds prosurvival Bcl-2 family proteins such as Bcl-w and Bcl-XL to liberate Bax, which in turn exerts proapoptotic or anti-invasive functions depending on stress context. On the basis of our previous finding that p53 interacts with p21, we investigated the possible involvement of p21 in these functions. Here, we report that although p53 can bind Bcl-w alone, it requires p21 to liberate Bax to suppress cell invasion and promote cell death. p21 bound Bcl-w, forming a p53/p21/Bcl-w complex in a manner that maintained all pairwise p53/p21, p21/Bcl-w, and p53/Bcl-w interactions. This allowed Bax liberation from the complex. Accordingly, a p53 derivative incapable of binding p21 failed to mediate radiotherapy-induced tumor cell death in mice. Bcl-XL also served as a target of the cooperative action of p53 and p21. Overall, our findings indicate that the p53/p21 complex rather than p53 itself regulates cell invasion and death by targeting Bcl-2 proteins. We propose that the p53/p21 complex is a functional unit that acts on multiple cell components, providing a new foundation for understanding the tumor-suppressing functions of p53 and p21. Cancer Res; 77(11); 3092–100. ©2017 AACR.
Continuous low-irradiance photodynamic therapy (CLIPT) as a novel treatment for cutaneous recurrences of breast cancer.
Authors: Justin Persico, David E. Wazer, Anne Marie Melanson, Gary S Rogers, Roger Graham
Journal: Journal of Clinical Oncology (2012)

e11548 Background: Photodynamic therapy (PDT) has been used for the treatment of many malignancies. This binary therapy involves the administration of a photosensitizer followed by exposure to light. Treatment toxicity has historically limited the use of PDT. Our study aimed to assess whether a novel approach, termed continuous low irradiance photodynamic therapy (CLIPT), would result in enhanced efficacy with reduced toxicity. Preclinical data suggest decreased toxicity and increased cell death by apoptosis with CLIPT. Methods: Breast cancer patients with chest wall progression were eligible for our study. No systemic anti-cancer therapy within 30 days and no radiation to the target site within 60 days of enrollment was allowed. All patients received porfirmer sodium intravenous 0.8mg/kg at time 0 and returned at time 48 hours for light exposure. A wavelength of 630nm was delivered continuously over 24 hours by a Diomed laser via a flexible light patch. An area of uninvolved normal skin was used as a control. Post-treatment biopsy was performed to assess for apoptosis by TUNEL assay. Results: Eight breast cancer patients were enrolled in our study. The initial dose of light was 100J/cm2 and was given to subjects 1 and 2 but resulted in partial-thickness ulceration of the epidermis. Subjects 3-8 received light at 50J/cm2 and experienced erythema at the intervention site, with no ulceration observed. All patients reported mild pain at the treatment site and 6 required short-term narcotic analgesia. Five of the 8 patients showed evidence of response, and no patients had progression of treated lesions. Four of 7 biopsy specimens showed evidence of apoptosis on TUNEL assay. Conclusions: CLIPT may prove to be a valuable option for treatment of breast cancer chest wall recurrence. The dose-limiting toxicity was skin ulceration and the maximum tolerated dose (MTD) was determined to be 50J/cm2/24h. A 50% response rate was seen in patients treated at the MTD, with apoptosis seen on post-treatment biopsy specimens. Further investigation of CLIPT as a therapeutic modality is warranted.
Blastic Plasmacytoid Dendritic Cell Neoplasm Evaluated by FDG PET/CT
Authors: Zu-Gui Li, Hai-Yu Mu
Journal: Clinical Nuclear Medicine (2017)

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological malignancy. A 34-year-old man with a biopsy-proven BPDCN underwent FDG PET/CT for staging. FDG PET/CT revealed multiple mild FDG-avid cutaneous lesions on the chest and back, involvement of left inguinal lymph node, and a markedly increased FDG-avid subcutaneous mass in the left lower leg.
Pheochromocytoma and Paraganglioma Susceptibility Genes
Authors: Lauren Fishbein, Katherine L. Nathanson
Journal: JAMA Oncology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
A Novel BRCA1-Associated Protein-1 Isoform Affects Response of Mesothelioma Cells to Drugs Impairing BRCA1-Mediated DNA Repair
Authors: Rossella Parrotta, Agata Okonska, Manuel Ronner, Walter Weder, Rolf Stahel, Lorenza Penengo, Emanuela Felley-Bosco
Journal: Journal of Thoracic Oncology (2017)
Physicians’ attitudes toward systematic symptom assessment and management: Results from all regional cancer centres in Ontario (Canada).
Authors: Martin Robert Chasen, Christopher Klinger, Michael Donald Brundage, Esther Green, Monika K. Krzyzanowska, Wenonah Mahase, Sean Molloy, Reena Tabing, Heidi Amernic, Serena Kurkjian, Omid Shabestari, Ravi Bhargava, Jose Pereira
Journal: Journal of Clinical Oncology (2015)

e17678 Background: Cancer patients experience a high symptom burden throughout the illness trajectory. Evidence suggests that the use of systematic symptom assessment instruments - such as the Edmonton Symptom Assessment System (ESAS) - might lead to better patient outcomes in terms of symptom management. Methods: Exploratory mixed methods approach. As part of a larger study, an electronic 21-item questionnaire concerning provider attitudes toward systematic symptom assessment and management was sent to all 960 physicians (general practitioners in oncology, medical oncologists, radiation oncologists, surgical oncologists and palliative care physicians) providing care at the Province of Ontario’s 14 Regional Cancer Centres in Spring of 2014. Systematic content analysis, descriptive statistics and Kendal Tau tests were utilized for data analyses, with Fisher’s Exact test employed for sub-group comparisons. Results: 256 physicians responded (27% response rate). Varying across Regional Cancer Centres and disciplines, the majority (66%) agreed that the regular use of standardized symptom assessment instruments should be considered ‘best practice’, with a range from 59% (surgical oncologists) to 97% (palliative care physicians). ESAS was overall seen as a useful starting point to assess symptoms (66%) and assisting with their documentation (59%). However, 53% of respondents revealed challenges to include the ESAS into the care plan, while 56% did not experience an enhancement of the efficiency of the meeting with the patient. Physicians with over 10 years of experience were more likely to: (i) look at their patients’ ESAS scores (p = 0.702) and (ii) talk to their patients about their ESAS scores (p = 0.362). Qualitative responses revealed some misperceptions about the use of standardized screening tools. Conclusions: Despite high regard toward usefulness and recognition as ‘best practice’, a gap toward the utilization of standardized symptom assessment instruments in daily practice/inclusion into the care plan does exist. Future research needs to explore the reasons for this disconnect and focus on avenues to overcome them to further enhance person-centered care.
Phase II study of HSPPC-96 in combination with GM-CSF and IFN-α in stage IV malignant melanoma
Authors: G. Parmiani
Journal: Journal of Clinical Oncology (2004)

7510 Background: We reported that vaccination with melanoma-derived HSPPC-96 resulted in melanoma-specific T-cell response (50%) and in clinical response (18%) in patients with residual disease. To investigate whether immune reaction to HSPPC-96 can be modulated by cytokines, we administered HSPPC-96 together with GM-CSF s.c. and IFN-α systemically. Methods: Patients with AJCC stage IV melanoma (n = 28) were vaccinated with autologous tumor-derived HSPPC-96. Most patients (n = 25) had received prior chemo- and/or bio-therapy. All patients underwent surgery to harvest tumor tissue for vaccine production. Subsequent treatment consisted of: HSPPC-96 (25 μg s.c. on day 2); GM-CSF (75 μg s.c. on days 1, 2, 3); IFN-α (3 MU i.v., twice weekly). This was repeated over 4 weeks followed by 4 weeks of rest. Then, 4 additional injections of HSPPC-96 were given biweekly with GM-CSF over 3 days followed by 5 injections of IFN-α at 2 days intervals. Anti-melanoma T-cell response was assessed on pre and post vaccination PBMCs, by ELISPOT assay using melanoma as targets. Results: Treatment was well tolerated. Eighteen patients received at least 4 vaccinations and were considered evaluable. Of these, 2 were free of disease (DF) and 16 had residual melanoma post surgery. Of the DF subjects, 1 remained DF for 419 days. Of the 16 patients with residual tumor, 10 showed SD lasting from 97 to 372 days. Six of the 16 patients showed an increased number of anti-melanoma T cells after vaccination and all had SD. The remaining patients had PD. Conclusions: These results suggest that GM-CSF, at this dose and schedule followed by systemic IFN-α, do not increase T-cell responses post HSPPC-96 vaccination as compared to our previous study. However, the present results continue to suggest a potential immunogenic and anti-tumor effect of HSPPC-96 vaccine in patients with metastatic melanoma. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Antigenics Antigenics, Inc, New York
A phase II randomized study of oral seliciclib in patients with previously treated nasopharyngeal carcinoma
Authors: W. Yeo, B. Goh, C. Le Tourneau, S. R. Green, J. H. Chiao, L. L. Siu
Journal: Journal of Clinical Oncology (2009)

6026 Background: Seliciclib is a selective inhibitor of cyclin dependent kinases (CDKs) 2, 7 and 9. In a phase I study of 2 weeks of oral administration, clinical antitumor activity was observed in patients with treatment-naive nasopharyngeal carcinoma (NPC) and biological effects consistent with CDK inhibition were detected in tumor biopsy samples. We are conducting a multicenter, randomized phase 2 study to evaluate the safety and efficacy of prolonged administration of seliciclib in patients with previously treated NPC. The study has a lead-in phase where the safety and tolerability of 2 dosing schedules of seliciclib are to be confirmed in patients with advanced solid tumors (including NPC) before being used in the randomized phase of the study where only NPC patients are eligible to participate. The primary efficacy endpoint is 6-month progression free survival. Here we report interim findings from the lead-in phase. Methods: Eligible patients must be ≥18 years with previously treated NPC or other incurable solid tumors; must have measurable disease according to RECIST, ECOG 0–1, and adequate bone marrow, hepatic and renal function. The planned sample size is 6 to 12 patients per dosing schedule. A dosing schedule is considered tolerable for proceeding to the randomized phase if &lt;33% patients experienced dose-limiting toxicities (DLT) during the first treatment cycle. Results: Twenty-three patients (age 38 - 74) were enrolled and treated. DLTs were observed in 4 patients: grade 3 increase in ALT or AST (n=3), and treatment delay &gt; 2 weeks for grade 1 creatinine (n=1). Common adverse events (all grades, regardless of causality) included fatigue, nausea/vomiting, constipation, cough, fever, hypokalemia, hyponatremia, and elevation in ALT/AST, most of which were mild to moderate in intensity. Conclusions: These interim data confirm that both dosing schedules are tolerable for proceeding to the randomized phase. Majority of stable disease occurred in NPC patients. Updated data will be presented at the meeting. [Table: see text] No significant financial relationships to disclose.
Preclinical evaluation of PARP inhibition in breast cancer: Comparative effectiveness of olaparib and iniparib.
Authors: Maura B. Cotter, Aisling Pierce, Patricia M. McGowan, Louise Flanagan, Cecily Quinn, Denis Evoy, John Crown, Enda McDermott, Michael J. Duffy
Journal: Journal of Clinical Oncology (2012)

1042 Background: The main function of PARP1 is repair of single-strand DNA. Phase I/II clinical trials have shown that the PARP inhibitor, olaparib has efficacy in BRCA1/2-related breast cancer. Due to the similarities between BRCA1/2-associated and triple negative breast cancer (TNBC), we hypothesise that TNBC may also be sensitive to PARP inhibition. In order to assess this we addressed the effects of 2 PARP/PARP-like inhibitors, on a panel of breast cancer cell lines. Methods: PARP1 was measured by immunohistochemistry in 101 TNBC and 116 non-TN cancers. Comparative growth inhibitory capacity of olaparib and iniparib was evaluated using cell viability (MTT) and colony formation assays in 12 breast cancer cell lines (TN=7, non-TN=5). Results: Using immunohistochemistry, PARP1 staining was predominantly nuclear with some cytoplasmic staining. High staining intensity for PARP1 was found more frequently in ER-negative (p = 0.001), in high grade (p = 0.013) and in Ki67-positive ( p = 0.003) samples. Potentially important was the finding that high PARP1 staining intensity was detected more frequently in TN than non-TN samples (p = 0.0001). IC 50 concentrations across 12 cell lines ranged from 3.7-31 µM for olaparib and 13-70 µM for iniparib. No difference in sensitivity was observed between the TN and non-TN cell lines (by MTT). Olaparib also reduced the ability of cells to form colonies with IC 50 values ranging from &lt;0.01-2.5 µM. Addition of the CDKI inhibitor CDK1i (Calbiochem) to olaparib resulted in formation of significantly fewer colonies compared with either inhibitor alone, in a cell line dependent manner. Conclusions: Our results suggest that although PARP1 is expressed in the majority of breast cancer, significantly higher staining intensity was found in TN than non-TN samples. Furthermore, our work suggests that olaparib is a more potent inhibitor of the in vitro growth of breast cancer cells than iniparib. Combined inhibition of PARP1 with olaparib and CDK1 with CDK1i may be a way forward for the treatment of TNBC. Acknowledgement: The authors thank SFI (SRC award, 08/SRC/B1410 MTCI) for funding this work.
Persisting risk of hepatocellular carcinoma after hepatitis C virus cure monitored by a liver transcriptome signature
Authors: Atsushi Ono, Nicolas Goossens, Richard S. Finn, Warren N. Schmidt, Swan N. Thung, Gene Y. Im, Yujin Hoshida
Journal: Hepatology (2017)

Ono, Atsushi; Goossens, Nicolas; Finn, Richard S.; Schmidt, Warren N.; Thung, Swan N.; Im, Gene Y.; Hoshida, Yujin; on behalf of Precision Liver Cancer Prevention Consortium Author Information
Aggressive care at the end of life: A study of practice based factors in patients with stage IV cancer.
Authors: Mohammad Omar Atiq, Rahul Ravilla, Ajay Kumar, Sajjad Haider, Ji-Ling Tang, Konstantinos Arnaoutakis, Pooja Motwani, Eric R Siegel, Appalanaidu Sasapu, Fade A. Mahmoud, Sarah Elizabeth Harrington
Journal: Journal of Clinical Oncology (2017)

80 Background: Numerous studies established that early utilization of palliative care-hospice services are beneficial to cancer patients. To reduce the incidence of aggressive care in terminal cancer patients, we conducted a quality improvement study to identify pertinent risk factors and develop interventions. Methods: Through chart review, we retrospectively identified patients with stage IV cancer that were followed by oncology clinic and were admitted to the University Hospital between 8/1/2015-10/31/15. For those patients who died during the last hospitalization or were discharged to hospice care, we obtained demographic, cancer related and practice related variables listed in Table. We used Mann Whitney U test and multivariable regression to find effects of factors related to length of stay (LOS) and cost of stay (COS). Results: Length of stay was significantly prolonged in those receiving chemotherapy within the past month (6 vs 3 p=0.035). Multivariate analyses found that patients with goals of care documented in the clinic had lower COS by 36.7% and LOS by 46.7%. On average, an ICU stay resulted in COS 2.2 times higher. No significant difference was seen in LOS based on a documented palliative care clinic visit or presence of an advanced directive. Conclusions: We identified practice based factors that need improvement including earlier goals of care conversations and less chemotherapy at the end of life. Identifying end stage patients in earlier admissions, collaborating with palliative care, and adding goals of care documentation to clinic note templates, are all interventions we are studying to improve care for end stage cancer patients. [Table: see text]
Phase I /II study of carboplatin with weekly ifosfamide and docetaxel in recurrent or metastatic head and neck squamous cell cancers (HN-SCC)
Authors: B. Chauhan, H. Wanebo, R. Rathore, P. Chougule, T. Kennedy, N. Ready
Journal: Journal of Clinical Oncology (2004)

5601 Background: Patients with recurrent or metastatic HN-SCC have a poor outcome with standard therapy. Current triplet chemotherapy regimens while highly active have major toxicities, especially hematologic. We are evaluating a novel, dose dense outpatient triplet regimen of every 4 week Carboplatin (C) with weekly Ifosfamide (I) and Docetaxel (D). Methods: Treatment consisted of C AUC=5 day 1; I 1 gm/m2 days 1, 8, and 15; and D (20, 25, 30, or 35 mg/m2) days 1, 8 and 15 every 28 days. Mesna 1 gm/m2 was co-administered in 500 ml 0.9 NaCl with I. Three patients (pts) each were entered at each dose level of D. Eescalation was done if patients received > 80% of planned chemotherapy and no Dose Limiting Toxicity (DLT) was observed during cycle one for each cohort. Standard eligibility criteria for organ function were utilized. Toxicities were evaluated by the NCI common toxicity criteria. Results: Eleven pts have been enrolled since March '03 and all are evaluable for toxicity assessment. No DLT's have been observed till date and accrual continues at dose level 4. Dose reductions due to cytopenias have been noted at all 3 levels. Major cycle 1 toxicities are tabulated below. In subsequent cycles gr. 3 hypoalbuminemia (n=1), gr.3 hyponatremia (n=1), gr. 3 anemia (n=1), gr. 2 urticaria (n=1) and gr. 2 infection (n=2) were noted. No neuropathy has been reported. Conclusions: This novel triplet regimen of Carboplatin with weekly Docetaxel and Ifosfamide is well tolerated in this setting. No DLT's have been observed at the penultimate dose level. Accrual to the study is continuing. No significant financial relationships to disclose.