tbuckley/cabot-search huggingface dataset:
Concurrent paclitaxel, carboplatin and radiation therapy for locally advanced non-small cell lung cancer
Authors: Y. Nakanishi, M. Kawasaki, H. Yamasaki, K. Ninomiya, S. Takeo, S. Hayashi, K. Oishi, M. Kuba, K. Takayama, N. Hara
Journal: Journal of Clinical Oncology (2004)

7336 Background:Standard therapy for inoperable stage III NSCLC is chemoradiotherapy. But optimal combination of these two modality is not established. To evaluate the efficacy and safety of chemoradiotherapy with a concurrent use of paclitaxel and carboplatin plus thoracic radiation for locally advanced NSCLC. Methods:The study is a phase II multi-institutional trial. Eligible patients had inoperable stage IIIA or IIIB disease, except cases with pleural or pericardial effusion, ECOG performance status 0 or 1, and no previous treatment. Paclitaxel (45 mg/m2) and carboplatin (AUC = 2) were administered every 7 days for 10 weeks. When PR was observed, chemotherapy was extended upto 16 weeks. Radiation therapy were concurrently administered 1.8∼2.0 Gy/day for 5∼7 week (total 60∼65 Gy). Results:Registration has finished on December 2002. Among the 72 patients registared, 68 patients were eligible and toxicity was evaluated for the 68 patients. There were 16 patients with stage IIIA and 52 with stage IIIB disease. The median age was 63.5 years (38–74). There were 33 patients with adenocarcinoma, 31 with squamous cell carcinoma and 3 with large cell carcinoma, one with undifferentiated carcinoma. The hematologic toxicities >= grade 3 were 24% leukopenia, 6% neutropenia, 3% thrombocytopenia, 12% anemia. There were 3 cases with treatment related death. One patient died of pulmonary toxicity, one with hemorrhage due to radiation necrosis, and one with pneumocystis carinii pneumonia which occurred after the recovery from hematologic toxicity. The response rate (intent-to-treat base) was 65% with 4 CR, 40 PR. Median follow-up time was 28 months and median survival has not been reached, and 1 year- and 2 year-survival (estimated survivals) were 57% and 41%, respectively. Conclusions:Concurrent use of radiation and paclitaxel plus carboplatin is active and promising regimen to stage III NSCLC. Updated survival data is to be presented. No significant financial relationships to disclose.
A study of pre-operative (neoadjuvant) letrozole in combination with bevacizumab in post-menopausal women with newly diagnosed operable breast cancer: A preliminary safety report
Authors: A. Forero-Torres, I. Percent, J. Galleshaw, L. Nabell, J. Carpenter, C. Falkson, C. Jones, H. Krontriras, J. De Los Santos, M. Saleh
Journal: Journal of Clinical Oncology (2007)

11020 Background: Our preclinical studies suggest that up-regulation of tumor cell VEGF is a mechanism to subvert estrogen dependence in hormone responsive breast cancer resulting in reduced efficacy or acquired resistance; we hypothesized that the combination of Bevacizumab (an anti-VEGF MoAb) and hormonal therapy would be more effective than hormonal therapy alone for breast cancer. Methods: Post-menopausal patients with ER and/or PR positive and Her-2-neu negative operable (T2–4a-c/N 0–2/M0) breast cancer were enrolled. Patients received letrozole (2.5 mg po daily) and Bevacizumab (15 mg/kg IV q 3 wks). Patients were reevaluated every 6 wks for a total of 24 wks; patients with CR/PR/SD in the first evaluation continued in the trial; after an additional 6 weeks of therapy patients with PD or SD were taken off-study and only patients with PR/CR completed 24 weeks of therapy. Definitive surgery was performed at the discretion of the surgeon no sooner than 4 wks after the last dose of bevacizumab. Patients continued letrozole while waiting for surgery. Up to December 2006, 27 patients have been enrolled with 13 patients too early to evaluate. Results: The 14 patients off-study had a median age of 63 years (range; 56 to 79) and an ECOG score of 0 for all patients. None of the patients received therapy for breast cancer before enrollment in the trial. 11 patients were stage II and 3 patients stage III. No treatment-related severe adverse events were seen. Treatment related toxicities were: grade 3 hypertension (n=1), grade 2 hypertension (n=7), grade 2 fatigue (n=2), grade 2 joint pain (n=3), grade 2 hot flashes (n=2), grade 1 proteinuria (n=1); 2 patients were taken off-study because of uncontrolled hypertension occurring on initial infusion of bevacizumab (not evaluable for efficacy). Of the 12 patients evaluable for response, 2 patients had pCR, 8 PR and 2 PD (at 9 weeks and 16 weeks). There have been no problems with wound healing or bleeding related to surgery or progressive disease while awaiting surgery. Conclusions: Combination letrozole and bevacizumab has substantial clinical efficacy and is well tolerated. The combination therapy will be evaluated in a randomized Breast Cancer Research Consortium Trial. [Table: see text]
The role of EGFR trafficking in neuroblastoma
Authors: P. E. Zage, Q. Yan, L. Zeng, A. J. Bean
Journal: Journal of Clinical Oncology (2007)

20003 Background: Signaling through growth factor receptors is important in neuroblastoma pathogenesis. Chromosome 1p36 is commonly deleted in neuroblastoma tumors and is associated with a poor prognosis. UBE4B, a gene in 1p36, has been reported mutated in high- risk neuroblastoma. We have found a direct interaction between UBE4B and hrs, a protein required for epidermal growth factor receptor (EGFR) trafficking, suggesting a link between EGFR trafficking and neuroblastoma pathogenesis. We have analyzed the role of UBE4B in the EGFR pathway in neuroblastoma cell lines. Methods: The expression of UBE4B, hrs and EGFR were analyzed by quantitative Western blot in a panel of 7 human neuroblastoma cell lines (SHEP, SKNAS, SKNSH, KCNR, SY5Y, LA155N, NGP). EGFR degradation rates were determined by examining the kinetics of cellular EGFR depletion following a pulse of ligand. Results: UBE4B levels were lowest in SKNAS and highest in NGP cells. Hrs levels were lowest in SKNSH cells and higher in other cell lines. EGFR levels were lowest in NGP and KCNR and highest in SKNAS cells. UBE4B levels were correlated with known 1p deletions. EGFR degradation rates were slowest in SKNAS cells and therefore correlated with cellular UBE4B levels. The low degradation rates were correlated with high cellular levels of EGFR. Conclusions: Expression levels of UBE4B are correlated in neuroblastoma cell lines with chromosome 1p deletions. Cell lines with lower levels of UBE4B degrade EGFR at a markedly slower rate, correlated with higher cellular EGFR levels. We hypothesize that UBE4B affects cell growth by interacting with hrs, directing EGFR for degradation. In its absence the ability of a cell to sort growth factor receptors for degradation is inhibited, resulting in growth factor receptor overabundance and uncontrolled cell growth. These results support the testing of EGFR inhibitors in a future phase I trial for children with neuroblastoma. No significant financial relationships to disclose.
Overview: foundations of cultural psychiatry
Authors: A R Favazza, M Oman
Journal: American Journal of Psychiatry (1978)

The authors demonstrate the significance of adding the cultural dimension to basic psychiatric concepts. They point out the areas in which the work of anthropology and social psychology are relevant to psychiatry, including understanding mental health and illness, child-rearing practices and their effects on personality, cognition, family and social networks, sex roles and behavior, alcohol use, communication, and therapy. They also present some of the major conceptual foundations of cultural psychiatry, which include ethnography, emic and etic approaches, the cross-cultural approach, and the study of subjective culture.
Analyzing white blood cell subpopulation for quick and simple predictors for autologous stem cell collection
Authors: Y. Gao, S. Lim, F. Gao, J. Ng, Y. Phoon, C. Tham, R. Quek, M. Tao
Journal: Journal of Clinical Oncology (2009)

7101 Background: For patients undergoing peripheral stem cell harvesting, the current standard predictor for successful harvest is the peripheral blood (PB)CD34 count, which may have a slow turn-around time. Daily monitoring of CD34 count may not be cost-effective. This study aims to identify simple hematological parameters that can be used to predict for a single day CD 34+ stem cell yield of at least 1 x 10(6)/kg. Methods: 57 patients with lymphoproliferative malignancies who underwent autologous stem cell (ASC) harvesting were studied following DHAP, ICE or ESHAP chemotherapy. Eight main parameters were investigated to predict for a single day CD34 stem cell yield above 1x10(6)/kg: PB CD34+ cells, absolute monocyte count (AMC), AMC ratio, total white count (WBC), absolute lymphocyte count (ALC), ALC ratio, immature granulocyte count (IMC), IMC ratio and non-neutrophil cells (NNC). NNC was calculated by subtracting absolute neutrophil count from the total white count. The ratios were calculated by dividing the respective values on the first day of harvest with the values on the day before mobilizing chemotherapy started. Results: Linear regression showed a strong correlation between stem cell yield and CD34+ cells (R2=0.79, p&lt;0.001), IMC ratio (R2=0.51, p&lt;0.001) and AMC ratio (R2= 0.46, P&lt;0.001). WBC and AMC showed a wide dispersion of results and were not reliable predictors of CD34 yield. On multivariate analysis, an IMC &gt; 1 (p=0.03) and AMC ratio &gt; 1 (p=0.002), ALC ratio &gt; 1 (p=0.03) were independently predictive of a single day CD34 stem cell yield exceeding 1x10(6)/kgConclusions: Incorporating simple, routine hematolgic indices such as ALC and AMC ratio into a simple formula can be used to predict for ASC collection in addition to CD34+ count. This may be particularly useful when the turn-around-time to attain enumeration of CD34+ cells is slow or delayed on the same day of collection. No significant financial relationships to disclose.
Physiological ranges of matrix rigidity modulate primary mouse hepatocyte function in part through hepatocyte nuclear factor 4 alpha
Authors: Seema S. Desai, Jason C. Tung, Vivian X. Zhou, James P. Grenert, Yann Malato, Milad Rezvani, Regina Español‐Suñer, Holger Willenbring, Valerie M. Weaver, Tammy T. Chang
Journal: Hepatology (2016)

Matrix rigidity has important effects on cell behavior and is increased during liver fibrosis; however, its effect on primary hepatocyte function is unknown. We hypothesized that increased matrix rigidity in fibrotic livers would activate mechanotransduction in hepatocytes and lead to inhibition of liver-specific functions. To determine the physiologically relevant ranges of matrix stiffness at the cellular level, we performed detailed atomic force microscopy analysis across liver lobules from normal and fibrotic livers. We determined that normal liver matrix stiffness was around 150 Pa and increased to 1-6 kPa in areas near fibrillar collagen deposition in fibrotic livers. In vitro culture of primary hepatocytes on collagen matrix of tunable rigidity demonstrated that fibrotic levels of matrix stiffness had profound effects on cytoskeletal tension and significantly inhibited hepatocyte-specific functions. Normal liver stiffness maintained functional gene regulation by hepatocyte nuclear factor 4 alpha (HNF4α), whereas fibrotic matrix stiffness inhibited the HNF4α transcriptional network. Fibrotic levels of matrix stiffness activated mechanotransduction in primary hepatocytes through focal adhesion kinase. In addition, blockade of the Rho/Rho-associated protein kinase pathway rescued HNF4α expression from hepatocytes cultured on stiff matrix.Fibrotic levels of matrix stiffness significantly inhibit hepatocyte-specific functions in part by inhibiting the HNF4α transcriptional network mediated through the Rho/Rho-associated protein kinase pathway. Increased appreciation of the role of matrix rigidity in modulating hepatocyte function will advance our understanding of the mechanisms of hepatocyte dysfunction in liver cirrhosis and spur development of novel treatments for chronic liver disease. (Hepatology 2016;64:261-275).
Anemia and physical function in older women with gynecologic cancer.
Authors: A. Ferrini, G. F. Colloca, F. Cerullo, G. Gambassi, M. Cesari
Journal: Journal of Clinical Oncology (2010)

e19510 Background: Anemia is very common in older cancer patients, and it is independently associated with negative health outcomes (e.g. disability, mortality). Although physical function and hemoglobin (Hb) concentration are crucial for a comprehensive evaluation of older cancer patients (affecting access to antineoplastic therapies), their relationship has never been formally explored. Aim of the study is to explore the relationship between Hb concentration and physical function in older cancer patients. Methods: Data are from the first 27 older women (mean age 72.9 [SD 6.0] years) with gynecologic cancer evaluated in an ongoing prospective study performed in an oncogeriatric unit. Physical function was measured by typical oncological (i.e. Karnofsky [KPS] and Eastern Cooperative Oncology Group Performance status [ECOG]) and geriatric (i.e. Activities of Daily Living [ADL], Instrumental ADL [IADL], and the Short Physical Performance Battery [SPPB]) scales. Unadjusted and adjusted (Model 1: age; Model 2: age, Modified Cumulative Illness Rating Scale) linear regression models exploring the association between Hb (independent) and physical function measures (dependent; per 1 SD increase) were performed. Results: Mean Hb concentration was 11.5 (SD 1.8) g/dL. Results (beta coefficient [SE]) from linear regressions are reported in the Table. Conclusions: Hb is inversely associated with physical function in older cancer patients. Stronger associations were reported (in decreasing order) for SPPB, ADL, and ECOG. In performing comprehensive geriatric assessment of older cancer patients, these three measures may represent better tools to use because able to capture underlying biological conditions (i.e. low Hb concentration). Unadjusted Model 1 Model 2 SPPB 0.315 (0.107) p = 0.008 0.373 (0.114) p = 0.004 0.343 (0.153) p = 0.04 ADL 0.353 (0.101) p = 0.002 0.372 (0.112) p = 0.004 0.307 (0.135) p = 0.04 IADL 0.254 (0.107)p = 0.03 0.289 (0.117)p = 0.02 0.226 (0.141)p = 0.13 KPS 0.213 (0.124)p = 0.10 0.239 (0.136)p = 0.09 0.114 (0.163)p = 0.49 ECOG -0.257 (0.103)p = 0.02 -0.294 (0.106)p = 0.009 -0.203 (0.104)p = 0.06 SDs: SPPB: 3.491; ADL: 1.577; IADL: 2.535; KPS: 11.773; ECOG: 0.537. No significant financial relationships to disclose.
The H1N1 influenza pandemy and pneumonia in Iceland 2009-2010: A one year follow up study
Authors: Hronn Hardardottir, Oskar Einarsson, Olafur Gudlaugsson, Kristbjorn Reynisson, Sigridur O. Haraldsdottir
Journal: European Respiratory Journal (2011)

Background: The influenza A (H1N1) pandemy in 2009 caused in a minority of infected severe pneumonia and respiratory failure.

Aims: To characterise patients admitted to our hospital with H1N1 influenza A infection and pneumonia and at one year follow up.

Methods: Patients with positive tests for H1N1 influenza and pneumonia with flulike illness and no other known pathogen were contacted 6 and 12 months after admission. Clinical examination with specific questionnaires (SI-36, HAD and St. George questionnaires) along with spirometry were performed to collect information on pulmonary symptoms, pulmonary status and health-related quality of life. Radiographs were reviewed and repeated when abnormal.

Results: 84 patients (42 women and 42 men) were admitted with influenza associated pneumonia. Th mean age was 51 years and mean BMI 33. The mean total hospital stay was 10 days. 50% of the patients required high-flow oxygen, and 25% of patients were admitted to the Intensive Care Unit. There was one death during the initial hospitalisation due to sequelae from H1N1.

44 patients participated in the follow up study. After 6 months only 3 patients had residual radiographic changes. Pulmonary function after 6 months in the patients admitted to the ICU were: FVC 102%, FEV1 100%, TLC 85% and DLCO 81% of predicted. Currently we are evaluating patients at the 1 year follow up including health-related quality of life.

Conclusions: The H1N1 pandemy in Iceland resulted in pneumonia with considerable morbidity. Our preliminary results indicate that the physiological and radiographic sequele are minor.
The use of a tandem serial measurement of circulating EBV DNA for the outpatient screening of EBV associated nasophayngeal carcinoma
Authors: A. W. Yeung, E. Ng, M. Law, C. N. Tam, T. S. Wong, A. Wan
Journal: Journal of Clinical Oncology (2005)

9617 Background: Epstein Barr virus (EBV) DNA has been found in the plasma of patients with nasopharyngeal carcinoma (NPC). The presence and quantity of EBV DNA has been used for the diagnosis, prognosis and monitoring of NPC patients. However, low copies of EBV DNA may also been found in a small percentage (1–3%) of normal individuals. This phenomenon may be due to the episodic lytic reactivations of the virus. The present study is to find out, by the use of a tandem and serial measurement of circulating EBV DNA in plasma, the positive and negative predictive value of this test for EBV positive nasopharyngeal carcinoma. Methods: Normal adults recruited during routine physicals and those with outpatient ear, nose and throat symptoms but with no confirmed diagnosis of cancer and age over 18 were admitted to the study. The quantity of circulating EBV DNA extracted from plasma was determined by a well described real-time PCR method using ABI Prism 7900 HT with specific primers and probe against the W1 fragment from the EBNA-LP region of the EBV genome. A second measurement of any positive case was offered to that individual 4–12 weeks after the first. All cases were followed for one year. Results: In this study group, 74 out of 3987 cases were determined as having positive EBV DNA values. Among the 74 positive EBV DNA cases, 27 cases returned to have second measurements within a 4 to 12 week period from the first. All except one saw their EBV DNA titers reduced to zero at the second measurement. The one that still showed a positive EBV DNA had a 50% reduction of its quantity compared with the first. He was given a third measurement 6 weeks later and the result was then negative. No EBV associated nasopharyngeal carcinoma case was identified in this study group. Conclusions: The negative predictive value using a tandem measurement of plasma circulating EBV DNA with the second measurement done within 4–12 week from the first has been close to perfect for a group of normal individuals and those with outpatient ear, nose and throat symptoms. The study is still ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Plasmagene Biosciences Ltd. Plasmagene Biosciences Ltd.
Implications from long-term follow-up after breast-conserving therapy for patient selection and duration of follow-up: The Edinburgh experience
Authors: I. H. Kunkler, U. Chetty, W. Jack, G. Kerr, J. Thomas, J. M. Bartlett
Journal: Journal of Clinical Oncology (2008)

555 Background: There are a few large population-based series assessing the long-term outcomes of breast-conserving therapy (BCT). Methods: A consecutive series (1981–98) of 1,812 women managed by wide local excision and postoperative radiotherapy (45Gy in 20–25 fractions). Results: Mean age was 54.9 years, range 24–91. Median clinical tumor size was 20mm. Histology was no special type in 1,477 patients (78.8%), tubular in 95 patients and lobular in 121. Tumor grade was available in 1,734 patients (450 grade 1, 767 grade 2, and 517 grade 3). Of 1,725 patients with margin status recorded, there was involvement by IBC in 250 and DCIS in 50. Axillary surgery was node sample in 1,385 patients (76.4%), level III clearance in 391 patients, and level II dissection in 36. Axillary lymph nodes were histologically node negative in 1,318 patients (72.7%). Adjuvant systemic therapy was tamoxifen alone in 1,179 patients (65.1%) and other hormone therapy in 250 patients. 306 patients received chemotherapy with half these patients also receiving hormone therapy. Minimum follow-up was 7 years (median 10 years). There were 572 deaths, 329 with breast cancer present. Actuarial estimates of survival from all causes were 88.5% at 5 years and 77.2% at 10 years. Actuarial cause specific survival (CSS) was 91.2% at 5 years (95% CI 89.9%-92.5%) and 85.1% at 10 years. Significant (p<0.0001) prognostic factors for CSS were number of positive nodes, tumor grade, and pathologic tumor size. The relapse rate in the treated breast was 4.5% at 5 years, 8.5% at 10 years, 14.6% at 15 years and 19.2% at 20 years. The number of positive nodes, pathologic tumor size, and age were significant prognostic factors for breast relapse. Conclusions: Poor local control in women aged <40 questions the appropriateness of BCT in this age group. A constant local relapse rate of just under 1% per year throughout 20 years of follow-up suggests that follow-up should continue beyond 10 years. Age Number of patients 5-year ipsilateral breast relapse (%) <30 15 40.7 30-39 134 13.1 40-49 380 4.6 50-59 651 3.5 60-69 484 2.2 70- 148 5.1 No significant financial relationships to disclose.
Ipilimumab (Ipi) expanded access program (EAP) for patients (pts) with stage III/IV melanoma: 10 mg/kg cohort interim results.
Authors: Omid Hamid, Wen-Jen Hwu, Jon M. Richards, Jeffrey S. Weber, Jedd D. Wolchok, Mario Sznol, David R. Minor, Anna C. Pavlick, Walter John Urba, F. Stephen Hodi, Arvin Yang, Tracy Michener, Agnes Balogh, David F. McDermott
Journal: Journal of Clinical Oncology (2012)

8508 Background: The EAP (CA184-045), begun in 8/07, currently provides the largest safety database for Ipi outside of controlled clinical trials (CCTs) and included pts with brain metastases (BM) and primary ocular (OM) and mucosal (MM) melanoma. The EAP was amended in 10/08 to administer a 3 mg/kg dose based on the current label (Hodi et al. NEJM 2010). We now report interim data from pts treated in the US at 10 mg/kg from 8/07-10/08. Methods: Pts with unresectable Stage III or IV melanoma who progressed on at least 1 systemic therapy or had no alternate treatment options were eligible. Pts received 10 mg/kg Ipi i.v. q 3 wks up to 4 doses (induction) followed by 10 mg/kg q 12 wks (maintenance) until no longer clinically benefiting or unacceptable/unmanageable toxicity occurred. All serious adverse events (SAEs) and on-study deaths were collected; overall survival (OS) was assessed retrospectively. Results: Of 906 treated pts, 830 were included in the analysis; 39 from prior Ipi trials + 37 from sites whose IRB did not agree to collect OS were excluded. Pts got a median of 4 doses; 31% got ≥5 doses. ECOG 0/1/2 was 53%/39%/8% (1 pt was ECOG 3); 27% had BM, 5% had OM, and 4% MM. Primary reasons for discontinuation were disease progression (67%) and drug toxicity (11%). Incidence of drug-related SAEs was 27% with diarrhea 10%, colitis 8%, endocrinopathies 4%, and dermatitis 0.8%. 2 pts (0.24%) had on-study hepatitis SAEs, both considered drug-related and resulted in discontinuation. There were 3 (0.36%) drug-related intestinal perforations. 2 deaths (0.24%) were the outcome of drug-related SAEs; 1 multi-organ failure and 1 acute respiratory distress syndrome (both ≤70 days from last induction dose). 72 (9%) pts currently remain on treatment (i.e. &gt;3 years). Available OS data showed that 138 pts (17%) were still at risk after 3 years. For 27% of pts the last known alive date was &gt;30 days before data cutoff (with most &gt;2 yrs). Conclusions: Data from the US EAP must be interpreted with caution compared to CCTs. To date, incidence of SAEs for hepatitis and intestinal perforation, and drug-related death at 10 mg/kg Ipi monotherapy is consistent with that seen in BMS clinical trials. Durable OS (&gt;3 yrs) was observed in at least 17% of pts.