tbuckley/cabot-search huggingface dataset:
Paclitaxel with mitoxantrone, fluorouracil, and high-dose leucovorin in the treatment of metastatic breast cancer: a phase II trial.
Authors: J D Hainsworth, S E Jones, R G Mennel, J L Blum, F A Greco
Journal: Journal of Clinical Oncology (1996)

Paclitaxel is a highly active single agent in the treatment of breast cancer. However, its optimal incorporation into combination regimens awaits definition. In this phase II study, we added paclitaxel, administered by 1-hour infusion, to a previously described combination regimen that included mitoxantrone, fluorouracil (5-FU), and high-dose leucovorin (NFL).Forty-six patients with metastatic breast cancer received the following regimen as first- or second-line treatment: paclitaxel 135 mg/m2 by 1-hour intravenous (i.v.) infusion on day 1, mitoxantrone 10 mg/m2 by i.v. bolus on day 1, 5-FU 350 mg2/m by i.v. bolus on days 1, 2, and 3, and leucovorin 300 mg i.v. over 30 to 60 minutes immediately preceding 5-FU on days 1, 2, and 3. Courses were administered at 3-week intervals for a total of eight courses in responding patients.Twenty-three of 45 assessable patients (51%) had major responses. Previous chemotherapy, and in particular previous treatment with doxorubicin, did not affect response rate. The median response duration was 7.5 months. Myelosuppression was moderately severe, with 76% of courses resulting in grade 3 or 4 leukopenia. Hospitalization for treatment of fever during neutropenia was required in 13% of courses, and two patients died as a result of sepsis. Two patients developed severe congestive heart failure after a large cumulative anthracycline dose.This combination regimen was active as first- or second-line therapy for metastatic breast cancer, although its activity compared with other combination regimens or with paclitaxel alone is unclear. Myelosuppression was more severe than anticipated based on previous results with the NFL regimen or with paclitaxel administered at this dose and schedule as a single agent. The infrequent development of cardiotoxicity in these patients suggests that the paclitaxel/mitoxantrone combination may not share the problems previously reported with the paclitaxel/doxorubicin combination.
Active Monitoring of Travelers Arriving from Ebola-Affected Countries — New York City, October 2014–April 2015
Authors: Alexander J. Millman, Shadi Chamany, Seth Guthartz, Sayone Thihalolipavan, Michael Porter, Andrew Schroeder, Neil M. Vora, Jay K. Varma, David Starr
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

The Ebola virus disease (Ebola) outbreak in West Africa has claimed approximately 11,300 lives (1), and the magnitude and course of the epidemic prompted many nonaffected countries to prepare for Ebola cases imported from affected countries. In October 2014, CDC and the Department of Homeland Security (DHS) implemented enhanced entry risk assessment and management at five U.S. airports: John F. Kennedy (JFK) International Airport in New York City (NYC), O'Hare International Airport in Chicago, Newark Liberty International Airport in New Jersey, Hartsfield-Jackson International Airport in Atlanta, and Dulles International Airport in Virginia (2). Enhanced entry risk assessment began at JFK on October 11, 2014, and at the remaining airports on October 16 (3). On October 21, DHS exercised its authority to direct all travelers flying into the United States from an Ebola-affected country to arrive at one of the five participating airports. At the time, the Ebola-affected countries included Guinea, Liberia, Mali, and Sierra Leone. On October 27, CDC issued updated guidance for monitoring persons with potential Ebola virus exposure (4), including recommending daily monitoring of such persons to ascertain the presence of fever or symptoms for a period of 21 days (the maximum incubation period of Ebola virus) after the last potential exposure; this was termed "active monitoring." CDC also recommended "direct active monitoring" of persons with a higher risk for Ebola virus exposure, including health care workers who had provided direct patient care in Ebola-affected countries. Direct active monitoring required direct observation of the person being monitored by the local health authority at least once daily (5). This report describes the operational structure of the NYC Department of Health and Mental Hygiene's (DOHMH) active monitoring program during its first 6 months (October 2014-April 2015) of operation. Data collected on persons who required direct active monitoring are not included in this report.
Intracranial Metastatic Tumors: An Overview
Authors: Keiji Sano
Journal: Neuro-Oncology (1991)

The author presented statistical data from the Brain Tumor Registry in Japan which collected 3,728 cases of intracranial metastatic tumors. 64.3% of these tumors were single. Primary tumors were lung cancers (50%), breast cancers (11.5%), gastro-intestinal cancers (10.3%) and others. It was stressed that for patients with single brain metastases in good clinical conditions and without metastases to other organs and without recurrence at the primary tumor sites, aggressive surgical removal of metastatic tumors with postoperative radiotherapy was effective to obtain longer and useful survival. Search for better chemotherapeutic agents or immunotherapeutic agents, however, should be continued.
Treating nonagenarians with cancer
Authors: E. J. Crane, M. Extermann
Journal: Journal of Clinical Oncology (2006)

8542 Background: In the U.S., the number of cancer patients who are greater than age 85 is expected to quadruple in the next 50 years. Barriers exist to treating this patient population because of concerns of frailty, lack of inclusion in clinical trials, and unknown outcomes when treating this patient population. This single institution retrospective evaluation provides data regarding treatment outcomes for cancer patients ages 90 or older at the time of their treatment at this cancer center. Methods: The charts of all patients registered at the Moffitt Cancer Center who were age 90 or older at during their treatment/evaluation were eligible to be reviewed. The total number of charts eligible was 643. Included patients: 1) had a diagnosis of cancer, 2) had a clear treatment plan with at least two follow-up visits over a one month time period, 3) patients with only one evaluation would be eligible if a clear treatment plan was outlined and their death occurred within 6 months of their evaluation at this cancer center. To date, 329 charts have been reviewed which has yielded 121 patients who meet the inclusion criteria. Results: Preliminary evaluation of reveals that the most common diagnoses are breast cancer (14%), malignant melanoma (11%), head and neck cancer (9%), SCC of the skin (9%), and prostate cancer (8%). Treatment plans included surgery for 45% of the patients with 36% of the patients undergoing general anesthesia. Chemotherapy was administered to 6.8% of the patients, and hospice was recommended to 7.8%. One year after evaluation at this cancer center 54% of the patients were alive, and 42% were alive at 2 years. The average number of medications that these patients used was 5.5 and greater than 95% of the patients had an ECOG performance status of 1. Conclusions: These preliminary results indicate that the nonagenarian cancer patients are probably healthy given the low number of medications taken, indicating fewer comorbid conditions. These patients do have months to years of survival after their therapies which included surgery under general anesthesia and chemotherapy. Although the nonagenarian cancer patient population found at a referral center is likely to be healthier than that found in the community, these findings indicate that nonagenarians with few comorbidities and a good performance status can be successfully treated for their cancer. No significant financial relationships to disclose.
Clinical pharmacokinetics of bevacizumab following every 2- or every 3-week dosing
Authors: J. Gaudreault, R. Bruno, F. Kabbinavar, A. Sing, D. H. Johnson, J. Lu
Journal: Journal of Clinical Oncology (2004)

3041 Background: Bevacizumab (BV) is an IgG1 monoclonal antibody that inhibits all isoforms of VEGF-A. The addition of BV to irinotecan/5-FU/LV (bIFL) in patients with metastatic colorectal carcinoma resulted in a 34% reduction in the risk of death, as compared to bIFL alone (p=0.00004), and in a median survival increase from 15.6 to 20.3 months (Hurwitz, ASCO 2003). Due to its long elimination half-life, BV was administered every 2 or 3 weeks in Phase II and III clinical trials. This analysis further characterizes the impact of dosing schedules on BV exposure. Methods: A retrospective non-compartmental analysis was conducted to compare several measures of drug exposure, using observed data from 2 Phase II dose-ranging trials (1 study in colorectal carcinoma (AVF0780g) and 1 in non small cell carcinoma (AVF0757g)), where BV was administered at doses of 5 and 7.5 mg/kg every 2 or 3 weeks, respectively. Simulations (500 subjects) were also performed to compare drug exposure for different administration frequencies, using a 2-compartment population PK model that was recently developed based on data from 491 subjects from 8 clinical trials. Results: Observed and simulated steady-state concentrations following BV dosing at 2.5 mg/kg/week every 2 or 3 weeks, are presented in the table below: Conclusions: Administration of BV at 2.5 mg/kg/week every 2 or 3 weeks results in similar overall exposure, due to its slow clearance and long elimination half-life of 20 days. Thus, the frequency of BV administration can easily be coordinated with the schedule of administration of the cytotoxic agents. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Inc. Genentech, Inc. Genentech, Inc. Genentech, Inc. Genentech Inc.
Differential spatial expression and activation pattern of EGFR and HER-2 in human breast cancer
Authors: A. Fink-Retter, D. Gschwantler-Kaulich, G. Hudelist, R. Mueller, E. Kubista, K. Czerwenka, C. Singer
Journal: Journal of Clinical Oncology (2006)

20041 Background: Overexpression of HER family members is a well-established prognositc factor and identifies potential targets for antibody-based receptor blocking strategies. While several studies have analyzed the expression of HER-2 and other HER-family members in malignant tumors, considerably less is known about their expression and activation in non-involved breast tissue from breast cancer patients. Methods: We have therefore investigated the differential expression of EGFR, HER-2 and their tyrosinekinase activated forms (ptyr-1248 HER-2 and ptyr-845 EGFR) by using immunohistochemistry (IHC) in 64 tumor specimens containing malignant epithelium (a), non-malignant tissue located at the peritumoral margin (b), and univolved breast tissue obtained at a distance of at least more than 5 cm from the malignant tumor (c). Results: We found significantly higher HER-2 protein expression levels in malignant epithelium than in non-malignant epithelium (p = 0.000004, Fisher’s Exact Test). Stromal HER-2 was absent in any of the tissues investigated. Epithelial EGFR expression did not differ between the three tissue types, but stromal EGFR protein was significantly more common in peritumoral and non-involved distant tissues when compared to tumor tissues (p = 0.008, Fisher’s Exact Test). We only found one case of intratumoral epithelial ptyr-1248 HER-2 expression, and interestingley two cases in peritumoral and peripheral normal tissue. Furthermore, we did not observe ptyr-845 EGFR in any of the samples analyzed.We found a significant overall correlation between epithelial and stromal EGFR expression (r = 0.442; p &lt; 0.0001; Spearman’s Rho). Furthermore, we found a significant overall correlation between stromal EGFR expression and normal tissue type (r = 0.170; p &lt; 0.02; Spearman’s Rho), and an inverse correlation between epithelial HER-2 and normal tissue type (r = 0.492; p &lt; 0.0001; Spearman’s Rho). Conclusion: We have found a differential expression pattern of EGFR, HER-2, and activated HER-2 that is dependent on the spatial relation to a malignant tumor. Our observation of decreased intratumoral EGFR expression and the absence of activated EGFR suggest that, in contrast to HER-2, EGFR inhibition might not be an ideal target for antibody therapy. No significant financial relationships to disclose.
Targeting arachidonic acid pathway by natural products for cancer prevention and therapy
Authors: Nagendra Sastry Yarla, Anupam Bishayee, Gautam Sethi, Pallu Reddanna, Arunasree M. Kalle, Bhadrapura Lakkappa Dhananjaya, Kaladhar S.V.G.K. Dowluru, Ramakrishna Chintala, Govinda Rao Duddukuri
Journal: Seminars in Cancer Biology (2016)
SDX-105 (Bendamustine) inhibits growth of SU-DHL-1 and Daudi lymphoma xenografts in SCID mice
Authors: Sarath Kanekal, Brian Crain, Gary Elliott, Saira S. Singh
Journal: Cancer Research (2004)

4575  SDX-105 is a structurally and functionally unique anticancer agent and has been demonstrated to be effective and relatively more potent in vitro than other alkylators in a variety of cell lines resistant to traditional alkylating agents. We now report SDX-105 inhibits growth of SU-DHL-1 and Daudi lymphoma tumor xenografts in SCID mice. SU-DHL-1 or Daudi cells (6.5 X 106 or 1.0 X 107 cells per mouse, respectively) were inoculated subcutaneously into the flanks of SCID mice. After the tumors reached approximately 100 mm3, mice were administered SDX-105 (2 to 32 mg/kg/d i.p. for 5 days), and tumor growth and body weight were monitored for 28 days. SDX-105-treated mice showed dose- and time-dependent tumor growth inhibition compared to untreated controls in both tumors: Daudi tumor volumes in SDX-105-treated (15 mg/kg/d) mice on day 7, 14 and 21 were 124+/−15, 106+/−25 and 212+/−46 mm3 respectively. Control tumors grew relatively faster: the respective tumor volumes were 272+/−13, 712+/−94 and 1428+/−176 mm3. Tumor growth inhibition in SU-DHL-1 xenografts was effective as well: tumor volumes in SDX-105-treated (16 mg/kg/d) mice on day 6, 13 and 20 were 155+/−30, 256+/−77 and 509+/−146 mm3 respectively. The respective control tumor volumes were 443+/−79, 1031+/−85 and 1725+/−129 mm3. There was a significant body weight loss and a few mortalities at doses of 20 mg/kg/d and higher. Cyclophosphamide at a four fold higher dose (60 mg/kg/d) showed tumor growth inhibition comparable to that of SDX-105 (15 mg/kg/d). These data corroborate our previous in vitro efficacy data and provide the first in vivo evidence for its efficacy in human lymphoma xenografts.
The relationship between asthma and depression among adolescences in Zanjan
Authors: Akefeh Ahmadiafshar, Saman Afkhami Ardakani, Payman Nickmehr, Abdolreza Ghoraishi
Journal: European Respiratory Journal (2014)

Back ground:  Asthma is the most common chronic disease in children. Thus determination and treatment of co morbid factors such as depression in these patients could be valuable . The aim of this study was to investigate the association between asthma and depression among 13 to 15- year-old adolescents.    Method  :This cross sectional study were carried out among 1500 students who randomly selected from 20 schools of Zanjan city. Asthma were detected on the basis of ISAAC questionnaire . The similar number of students who didn9t have atopy or asthma were selected as control group. Depression was assessed by Beck questionnaire in both groups. Data was analyzed by SPSS software   Results : Two hundred and twenty five students (15%) had asthma and among them  20%, 23.6% and 18.2% had severe, moderate and mild depression, respectively.  Meanwhile in non asthmatic group 7.5%m 14.5% and 14.5% students had mild, Moderate and  severe depression; respectively. The students with asthma were significantly 2.87 (95%CI:1.96-4.26, p=0.0001) times more likely to have depression. There was also a significant correlation between severity of asthma and depression(P=0.0001).   Conclusion:  The prevalence of depression among children with asthma is higher. Thus attention to psychosocial factors in these patients and psychiatric intervention could beneficently improve asthma symptoms.
Population testing for cancer predisposing BRCA1/BRCA2 mutations
Authors: J Wardle
Journal: JNCI Journal of the National Cancer Institute (2014)

Background: Technological advances raise the possibility of systematic population-based genetic testing for cancer-predisposing
mutations, but it is uncertain whether benefits outweigh disadvantages. We directly compared the psychological/quality-of-life
consequences of such an approach to family history (FH)–based testing.
Methods: In a randomized controlled trial of BRCA1/2 gene-mutation testing in the Ashkenazi Jewish (AJ) population, we compared
testing all participants in the population screening (PS) arm with testing those fulfilling standard FH-based clinical criteria (FH
arm). Following a targeted community campaign, AJ participants older than 18 years were recruited by self-referral after pretest
genetic counseling. The effects of BRCA1/2 genetic testing on acceptability, psychological impact, and quality-of-life measures were
assessed by random effects regression analysis. All statistical tests were two-sided.
Results: One thousand, one hundred sixty-eight AJ individuals were counseled, 1042 consented, 1034 were randomly assigned
(691 women, 343 men), and 1017 were eligible for analysis. Mean age was 54.3 (SD = 14.66) years. Thirteen BRCA1/2 carriers were
identified in the PS arm, nine in the FH arm. Five more carriers were detected among FH-negative FH-arm participants following
study completion. There were no statistically significant differences between the FH and PS arms at seven days or three months
on measures of anxiety, depression, health anxiety, distress, uncertainty, and quality-of-life. Contrast tests indicated that overall
anxiety (P = .0001) and uncertainty (P = .005) associated with genetic testing decreased; positive experience scores increased
(P = .0001); quality-of-life and health anxiety did not change with time. Overall, 56% of carriers did not fulfill clinical criteria for
genetic testing, and the BRCA1/2 prevalence was 2.45%.
Conclusion: Compared with FH-based testing, population-based genetic testing in Ashkenazi Jews doesn’t adversely affect shortterm
psychological/quality-of-life outcomes and may detect 56% additional BRCA carriers.
Influx and apoptosis of activated effector memory T cells in both lungs of patients with unilateral non-small cell lung cancer (NSCLC)
Authors: V. S. Donnenberg, J. D. Luketich, R. J. Landreneau, A. M. Popovic, A. D. Donnenberg
Journal: Journal of Clinical Oncology (2004)

7373 Background: Local suppression of immunity is a potential mechanism for tumor escape from immune surveillance, and may represent an obstacle to immunotherapy. We previously reported high apoptosis of lung resident T cells in NSCLC, and the presence of regulatory/suppressor CD4 T cells. Methods: We used multi-parameter functional flow cytometry to measure the differentiation state, activation, and apoptosis of lung resident CD4 and CD8 T cells in matched broncho-alveolar lavage (BAL) samples from 5 healthy volunteers and 66 patients with unilateral resectable lung tumors with paired BAL ipsilateral and contralateral to the tumor. Results: In healthy subjects, BAL T cells were predominantly CD4+ (mean +/- SEM: 68 +/- 3%) and expressed a phenotype consistent with mucosal memory-effector T cells (CD45RO+, CD45RA-, CD103+, CD27-) (77 +/- 6% and 73 +/- 10%, for CD4+ and CD8+, respectively). 18+/-3% of normal lung resident memory T cells bound Annexin V, an early marker of apoptosis. Effector-memory cells also comprised the majority of CD4 and CD8 lung T-cells in NSCLC BAL (67 +/- 5 and 87 +/- 2%), but CD8 predominated (54 +/- 4%). The great majority of CD4 and CD8 effector-memory cells bound Annexin V (81 +/-3 and 80 +/- 14%), and were CD28- (42 +/- 4 and 77 +/- 3%). These cells also bore the late activation marker HLA-DR (65 +/- 4 and 33 +/- 6%), but were not in cycle as indicated by transferrin (CD71) expression. BALs obtained ipsilateral and contralateral to the tumor were indistinguishable by all comparisons. Conclusions: The data indicate that lung T cells respond as a physiological unit. This may result from a common inflammatory stimulus affecting both lungs, or alternatively may represent sympathetic inflammation as has been observed following eye trauma. In either case, the preponderance of apoptotic memory-effector cells expressing late activation markers without evidence of proliferation suggests the chronic influx and activation of memory cells, followed by their rapid death and clearance. No significant financial relationships to disclose.
Bevacizumab in pediatric cancer patients (pts): Safety concerns.
Authors: A. Jenkner, M. De Pasquale, A. Castellano, R. Pessolano, I. Ilari, M. De Ioris, F. Demelas, F. Del Bufalo, A. Serra, A. Donfrancesco
Journal: Journal of Clinical Oncology (2010)

e20002 Background: Bevacizumab (BV) is a monoclonal antibody against vascular endothelial growth factor (VEGF) with a reportedly acceptable safety profile and some antitumor activity also in pediatric cancers. Feasibility and toxicity of BV were evaluated in a case-series of children with recurrent or resistant solid tumors. Methods: Pts received intravenous BV at 5-10 mg/kg every 14-28 days. 12 pts had a relapsed/refractory solid tumor while 5 pts had a poor prognosis tumor. The diagnoses were: relapsed metastatic neuroblastoma (7), relapsed rhabdomyosarcoma (4), hepatocellular carcinoma (3), metastatic renal cell carcinoma (1), Ewing sarcoma (1) and abdominal mesothelioma (1). Toxicity was reported according to CTC version 3. Results: 17 pts, M/F 9/8, median age 112 months (range 30-222) received a total of 156 courses, with a median of 5 courses per patient (range 2-25). BV was used in combination with chemotherapy in 15 pts, with sunitinib in one pt and was administered alone in one pt. Median treatment duration was 2 months (range 1-26). 9/17 patients progressed during treatment after a median progression-free survival of 2 months (range 1-13). Two patients (both hepatocellular carcinoma) are still receiving BV 21 and 26 months since diagnosis, while one pt (relapsed rhabdomyosarcoma) stopped treatment after 6 months in CR. One patient refused to continue treatment after one month while four patients discontinued treatment after a median of 5 months (range 3-21) for occurrence of severe adverse events (SAE). Grade II-III lymphopenia was reported in 11 patients while a grade III proteinuria and grade I epistaxis were recorded in one patient each. SAE were: 1) a reversible posterior leukoencephalopathy syndrome with grade IV seizures and grade IV severe hypertension, 2) postoperative grade IV entero-cutaneous fistula, 3) grade IV wound dehiscence and 4) grade IV hypertension. Conclusions: In this case series, the incidence of SAE (24%) was higher than previously reported. Further studies with BV alone or in homogeneous drug combinations are needed to better characterize the safety profile of BV in the pediatric patient population. No significant financial relationships to disclose.