tbuckley/cabot-search huggingface dataset:
Pattern of estrogen receptor positivity in breast cancer among the elderly
Authors: K. Cheung, D. A. Morgan, A. W. Wong, H. Parker, I. O. Ellis
Journal: Journal of Clinical Oncology (2007)

21122 Background: It is known that oestrogen receptor (ER) positivity in breast cancer increases with increasing age. Some clinical data show that radiotherapy can be safely avoided to achieve similar local control following lumpectomy in elderly patients taking tamoxifen; and that there is negligible benefit of adjuvant chemotherapy for patients approaching the age of 70. We postulate that biological differences (with ER being an important one) may be contributory. This study aimed to analyse the pattern of ER positivity in the elderly population. Methods: Among 2,061 patients &gt;70 years who had operable primary breast cancer (&lt;5cm) managed in a dedicated clinic from 1987, there were 1,557 tumours which had ER data available. Their pattern was studied and compared with that in 2,674 tumours from younger (= 70 years) counterparts treated during the same period in the same centre. Histochemical (H) score was measured using standard ER immunohistochemical assay and reported by the same team of dedicated breast pathologists. Results: The patterns of ER in different age groups are shown below. Conclusion: In all age groups there is a marked biphasal distribution of ER positivity, but in patients &gt;70 years this biphasal distribution is more marked than in other age groups , with a great preponderance of highly ER-positive tumours, and a substantial minority being ER-negative (H=0), with very few in intermediate groups. Endocrine therapy is clearly appropriate for the highly ER-positive majority, but management of those ER-negative ones (H = 0) is a challenge. [Table: see text] No significant financial relationships to disclose.
Detection of Philadelphia chromosome-positive acute lymphoblastic leukemia by polymerase chain reaction: possible eradication of minimal residual disease by marrow transplantation
Authors: K Miyamura, M Tanimoto, Y Morishima, K Horibe, K Yamamoto, M Akatsuka, Y Kodera, S Kojima, K Matsuyama, N Hirabayashi
Journal: Blood (1992)
PI3K signalling may explain differential response of lung cells to mechanical stretch
Authors: Stefan Hammerschmidt, Hartmut Kuhn, Hans-Jurgen Seyfarth, Christian Gessner, Hubert Wirtz
Journal: European Respiratory Journal (2012)

Alveolar epithelial cells may be subjected to increased mechanical stretch (MS) during ventilation although low tidal volume is applied. High amplitude MS impairs PI3K activity and leads to apoptosis in alveolar type II (ATII) cells. The response of human pulmonary microvascular endothelial cells (HPMEC), fibroblasts (HPF), human A549 cells and rat ATII cells to MS is compare in this study.

Stretching patterns (frequency/change in surface area) were chosen to mimic physiological breathing (P) and the effects of high frequency (hF), high amplitude (hA) and both (hFA). MS was compared with static cultures at 24h. Supernatant LDH, cell necrosis/apoptosis (Annexin-V binding/propidium iodide-staining) and cellular PI3K activity (measured as phosphorylated Akt-kinase, pAkt) were analyzed. MS increased the release of LDH in all cell types. This effect increased with the hF, hA and hFA stretching patterns. Viable HPMEC and ATII cells decreased significantly in response to MS with a minimum in the hFA and hA group; predominately due to apoptosis. A549 cells showed only a small decrease in viable cells with little change in necrotic and apoptotic cells. HPF, however, did not undergo apoptosis in response to MS. Cellular pAkt content was reduced in response to MS in HPMEC and ATII cells, unchanged in A549 cells and increased in HPF. PI3K stimulation increases the percentage of apoptotic cells.

In contradiction with endothelial and epithelial cells, pulmonary fibroblasts do not undergo apoptosis and show increased PI3K in response to MS. In lung injury fibroblast may remain as a scaffold for the pulmonary structure leading the way for repair.
The association between clinical characteristics, treatment modality, and outcomes of non-small cell lung cancer
Authors: J. Yorio, Y. Xie, J. Yan, D. E. Gerber
Journal: Journal of Clinical Oncology (2009)

7534 Background: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer death in the United States. NSCLC outcomes vary widely among patients. The degree to which these disparate outcomes reflect differences in treatment modality remains unclear. We therefore examined these associations at a medical center providing care to a diverse patient population. Methods: We performed a retrospective analysis of consecutive patients diagnosed with NSCLC stages I-III from 2000 to 2005 at the University of Texas Southwestern Medical Center. We recorded patient, disease, and treatment characteristics. The association between these characteristics and outcome was assessed using univariate analysis, multivariate logistic regression, and survival analysis. Results: A total of 482 patients met criteria for analysis. Mean age was 64 y, and 52 percent were men. For stage I/II disease, median survival was 6.7 y for patients aged &lt; 65 y vs 4.4 y for age ≥ 65 y (P=0.01); 3.1 y for men vs &gt;5.8 y for women (P=0.0002); 5.6 y for patients with household income below the national median ($41,995) vs 5.6 y for above-median income (P not significant). For stage III, median survival was 1.1 y for age &lt; 65 y vs 0.7 y for age ≥ 65 y (P=0.02); 0.8 y for men vs 1.2 y for women (P=0.02); 0.7 y for below-median income vs 1.2 y for above-median income (P=0.02). Race and hospital setting (public versus private) were not associated with survival. For stage I/II, patients treated with surgery had a median survival of 5.8 y, vs 1.7 y for non-surgical treatment (P&lt;0.0001). For stage III, patients who received surgery and/or radiation had a median survival of 1.2 y vs 0.5 y for other patients (P&lt;0.0001). For stage I/II, treatment modality was associated with hospital setting, race, and income. For stage III, treatment modality was associated with age, gender, hospital setting, race, and income. In multivariate analysis, age (for stage I/II), gender (for stage I/II), and treatment modality (for all stages) were associated with survival. Conclusions: For stages I-III NSCLC, a number of clinical characteristics are associated with outcomes. Differences in treatment modality may account in part for these disparities. These findings warrant further study. No significant financial relationships to disclose.
Lensless Imaging and Sensing
Authors: Aydogan Ozcan, Euan McLeod
Journal: Annual Review of Biomedical Engineering (2016)

High-resolution optical microscopy has traditionally relied on high-magnification and high-numerical aperture objective lenses. In contrast, lensless microscopy can provide high-resolution images without the use of any focusing lenses, offering the advantages of a large field of view, high resolution, cost-effectiveness, portability, and depth-resolved three-dimensional (3D) imaging. Here we review various approaches to lensless imaging, as well as its applications in biosensing, diagnostics, and cytometry. These approaches include shadow imaging, fluorescence, holography, superresolution 3D imaging, iterative phase recovery, and color imaging. These approaches share a reliance on computational techniques, which are typically necessary to reconstruct meaningful images from the raw data captured by digital image sensors. When these approaches are combined with physical innovations in sample preparation and fabrication, lensless imaging can be used to image and sense cells, viruses, nanoparticles, and biomolecules. We conclude by discussing several ways in which lensless imaging and sensing might develop in the near future.
Availability of whole-body positron emission tomography (PET) for the detection of metastatic sites in recurrent uterine sarcoma
Authors: M. Murakami, H. Tsukada, M. Ikeda, M. Watanabe, T. Muramatsu, T. Miyamoto, T. Makino, S. Yasuda, M. Ide, S. Nasu
Journal: Journal of Clinical Oncology (2004)

5100 Background: Uterine sarcomas are relatively rare and its prognosis is poor. About half of patients with stage I will have distant metastasis within two years after the complete operations. Accurate diagnosis of the metastatic sites is important for the treatment strategy. Unfortunately current diagnostic techniques, including CT, MRI, and ultrasonography (US) are not efficient for the detection of recurrence. There is little report of the experience with whole-body 18 fluorodeoxyglucose (FDG)-PET for the detection of recurrence in the follow up of patients with uterine sarcomas. The purpose of this study is to evaluate the availability of FDG-PET for the detection of recurrence in patients with uterine sarcomas. Methods: Twelve patients with pathologically proven uterine sarcomas (nine leiomyosarcoma and three carcinosarcoma) took FDG-PET, CT, MRI and US for the purpose of the detection of recurrence after the primary treatment. Post-void static images of PET were obtained in all cases to minimize bladder FDG activity. The final diagnoses of metastases were established by surgery or clinical follow-up for six months after the PET scan. Results: The final diagnoses of recurrence were established in five cases (three carcinosarcoma and two leiomyosarcoma). PET scan showed all recurrent sites of intraperitoneum, liver, lung and retroperitoneal lymph nodes. Images of CT scan showed false negative of intraperitoneal tumors in the two cases. Positive results of PET scan did not affect the prognosis in four patients, but another patient with solitary intraperitoneal tumor by PET scan could received the chemotherapy and operation, which histologically confirmed the recurrence of leiomyosarcoma. She survives now more than four years after the PET scan. Conclusions: Whole-body FDG-PET had high sensitivity for detecting both intraperitoneal and/or retroperitoneal metastases. PET was useful to detect solitary small intraperitoneal tumor, which was very difficult to detect by CT or US. Application of PET scan for the early detection of recurrence may affect the prognosis of some patients with uterine sarcoma. No significant financial relationships to disclose.
Impact of diabetes mellitus on complications of chemotherapy and outcomes in older patients with breast cancer
Authors: T. P. Srokowski, S. Fang, G. N. Hortobagyi, S. H. Giordano
Journal: Journal of Clinical Oncology (2008)

553 Background: Diabetes mellitus (DM) is a recognized risk factor for several cancers and it can affect treatment toxicities and cancer outcomes. To date no studies have reported on specific complications of chemotherapy in patients with breast cancer (BC) and DM. Effect of DM on BC outcomes is unclear as studies have found conflicting results. We evaluated how diabetes affects patterns of care, complications of chemotherapy, and BC outcomes. Methods: Using a SEER-Medicare database we identified women age 66 years or older with Stage I-III breast cancer diagnosed between 1992 and 2002. We used ICD-9 and other codes to identify patients with DM, chemotherapy use, and toxicities of therapy. Multivariate Cox logistic regression analyses were performed to determine effect of DM on chemotherapy use, related toxicities, and outcomes. The risks of all-cause mortality and BC-specific mortality were estimated with Kaplan-Meier method. Results: Our cohort had 70,781 patients including 14,414 (20.4%) patients with DM. DM was associated with reduced odds of receiving anthracyclines (OR 0.78, CI 0.71–0.87) and taxanes (0.86, 0.75–0.99). 1,850 (15.6%) patients experienced any toxicity of chemotherapy. DM was associated with increased odds of experiencing hospitalization for toxicity of chemotherapy (1.38, 1.23–1.56), and with hospitalizations for infection/fever (1.43, 1.2–1.7), neutropenia (1.22, 1.03–1.45), and anemia (1.24, 1.05–1.47). DM negatively influenced all- cause mortality (HR 1.35, CI 1.31–1.39). There was a significant interaction between DM and chemotherapy use for BC-specific mortality. DM patients who did not receive chemotherapy had similar BC-specific mortality to non-DM patients (0.95, 0.88–1.03), but diabetics who did receive chemotherapy had worse BC-specific mortality than non-diabetics (1.20, 1.07–1.35). Conclusions: Patients with BC and DM despite receiving less toxic chemotherapy regimens are at increased risk of toxicities and hospitalization. This group of patients needs especially close attention in selection of chemotherapy and monitoring for toxicities. DM is associated with significantly higher risk of all-cause mortality and with worse BC-specific mortality among patients receiving adjuvant chemotherapy. No significant financial relationships to disclose.
Metronomic chemotherapy (MC) with irinotecan (CPT-11) in patients with diagnosis of metastatic colorectal cancer (MCRC): clinical and pharmacodynamic evaluation
Authors: F. Loupakis, G. Bocci, G. Allegrini, E. Cerri, M. T. Barletta, G. Masi, A. Fioravanti, P. Orlandi, M. Del Tacca, A. Falcone
Journal: Journal of Clinical Oncology (2006)

13111 Background: Preclinical studies have demonstrated that the frequent administration of low doses of cytotoxic drugs over prolonged periods of time (MC) reduces tumour cell growth through inhibition of angiogenesis. The antitumor effect of a MC with cyclophosphamide is due to an increase of thrombospondin-1 (TSP-1) plasma level, an endogenous inhibitor of angiogenesis. Methods: An exploratory study was conducted to assess the feasibility, the activity and the optimal metronomic dose of CPT-11 when administered as protracted continuous infusion (c.i.) in pretreated MCRC. A pharmacodynamic evaluation of anti- and pro-angiogenic factors, such as TSP-1 and vascular endothelial growth factor (VEGF), was performed. Weekly blood samples were taken. Three different CPT-11 dose levels have been evaluated: 1.4, 2.8 and 4.2 mg/sqm/day; 25%, 50% and 75% of the maximum CPT-11 tolerated dose in c.i. (5.6 mg/sqm/day), respectively. Results: Between Apr 04 and May 05 20 patients have been enrolled. Patients characteristics were: M/F = 11/9, median age = 71 years (range 51–79); PS 0/1/2 = 8/11/1; sites of metastasis: single/multiple = 7/13; median of previous lines of chemotherapy: 3 (range 1–5). No toxicities of grade &gt;1 NCI scale have been observed. No objective responses were observed, but 4 patients (20%) had a stable disease with a median duration of 14 weeks (range 11–20). TSP-1 plasma levels significantly increased after one week and remained higher than the baseline for more than 8 weeks (120.1±10.3% vs. 100% of day 0). VEGF levels did not significantly change during the CPT-11 infusion. No statistical differences have been found for TSP-1 and VEGF concentrations among the three dose levels. Conclusions: CPT-11 metronomic chemotherapy is feasible. Plasma TSP-1 markedly increased during metronomic CPT-11 administration, suggesting a modulation of the angiogenic process in cancer patients. Supported by A.I.R.C. [Table: see text]
Effective Response Metric (ERM-D8) Using Time-Series Gene Expression Profiling at Diagnosis and Day 8 of Remission-Induction Therapy Is a Novel Early Prognostic Marker to Predict Relapse in Childhood Acute Lymphoblastic Leukemia (ALL) — a Malaysia-Singapore ALL Study
Authors: Allen Eng Juh Yeoh, Zhenhua Li, Difeng Dong, Yi Lu, Jan Trka, Shirley Kow Yin Kham, Ah Moy Tan, Hany Ariffin, Limsoon Wong
Journal: Blood (2014)
A randomized phase III study of maintenance therapy with bevacizumab (B), pemetrexed (Pm), or a combination of bevacizumab and pemetrexed (BPm) following carboplatin, paclitaxel and bevacizumab (PCB) for advanced nonsquamous NSCLC: ECOG trial 5508 (NCT01107626).
Authors: S. E. Dahlberg, S. S. Ramalingam, C. P. Belani, J. H. Schiller
Journal: Journal of Clinical Oncology (2011)

TPS218 Background: In ECOG 4599, bevacizumab was continued as maintenance therapy following 6 cycles of PCB. This study led to the approval of PCB followed by B for first-line treatment of advanced non-squamous NSCLC by the FDA. Switch maintenance therapy with Pm has recently demonstrated survival benefit for non-squamous NSCLC. Therefore ECOG 5508 will compare the efficacy of continuation of B vs. switch to Pm or the BPm combination after 4 cycles of PCB. Methods: The primary objective is to compare OS with B, Pm or BPm as maintenance therapy in pts with advanced stage NSCLC. Secondary objectives include PFS, response, toxicity and correlative studies focusing on polymorphisms, population pharmacokinetics and expression levels association with these outcomes. Eligibility criteria: ECOG PS 0 or 1 and adequate hematologic, renal and hepatic function, no brain metastases. All eligible pts receive PC (200 mg/m2, AUC=6 on day 1 every 3 wks) + B 15mg/kg day 1 (PCB) every 3 weeks. After 4 cycles pts with CR/PR/SD are randomized to B 15mg/kg day 1, Pm 500mg/m2 day 1, or BPm day1 until progression or intolerable toxicity. The study is designed to have 81% power to detect a 25% reduction in the hazard rate for death, while maintaining a Bonferroni-adjusted one-sided overall significance level of 0.0125 for each of B versus BPm and for B versus Pm. This corresponds to an improvement in post-induction median OS from 12 mos to 16 mos. Full information will be reached at 490 events per comparison. The randomization and the primary test will be stratified by gender, stage, smoking history and response. Unique design features: If the B versus BPm comparison reaches criteria for demonstrating futility, the combination arm will be dropped and the B arm and the Pm only arm will continue as planned. If the B arm is shown to be inferior to the BPm arm, then the B only arm will be dropped. At that point, if the estimated OS hazard ratio comparing Pm to BPm is less than 1.2, consideration will be given to amending the trial to address a noninferiority question between these two arms. Current enrollment is 18 out of 1282 planned pts.
Medical histories of delinquent and nondelinquent children: an epidemiological study
Authors: D O Lewis, S S Shanok
Journal: American Journal of Psychiatry (1977)

The authors studies the hospital records of 109 delinquent children and a matched comparison group of 109 nondelinquent children. The number, reasons for, and timing of hospital contacts significantly differentiated the delinquent from the nondelinquent children; perinatal difficulties did not. The authors hypothesize that an interaction of developmental factors and parental inadequacies accounts for the clustering of hospital contacts before age 4 and between ages 14 and 16 in the delinquent sample. They discuss the implications of their findings for prevention.
Enhancing DNA repair in the skin: A pilot study of low-dose chloroquine and ultraviolet light.
Authors: H. E. Kanavy, M. A. Warycha, H. Hamilton, A. Souza, I. Osman, L. Chiriboga, H. Yee, N. Soter, B. Strober, D. Polsky
Journal: Journal of Clinical Oncology (2010)

8566 Background: Inability to repair ultraviolet light (UV)-induced DNA damage causes skin cancer. Chloroquine has been shown to activate the DNA damage response pathway. The aim of this pilot study is to determine the potential role of chloroquine in skin cancer chemoprevention through upregulation of DNA damage repair pathways. Methods: Thirty subjects aged 23-60 years with fair skin were enrolled. Each subject was given chloroquine 500 mg per week for 4 weeks. The minimal erythema dose (MED) of artificial UV light was determined for each subject, and skin biopsies of MED sites (24 hours after UV exposure) were obtained before and after chloroquine therapy. DNA damage was assessed using immunohistochemical detection of thymine dimers; activation of p53 was assessed by detection of its downstream target p21. Image analysis was performed with Aperio Digital Pathology software. Our hypothesis is that chloroquine upregulates DNA repair pathways prior to UV irradiation leading to increased repair of UV-induced DNA damage. Twenty-four hours after UV irradiation we expect to observe less DNA damage and lower p21 levels in skin biopsies after chloroquine treatment than before treatment. Results: Fifteen of 30 subjects showed an increase in MED, indicating decreased sensitivity to UV light after chloroquine treatment. Six subjects had MED increases of 200 mj/cm2 and 9 had increases of 100 mj/cm2. Fourteen subjects showed no change in MED and 1 subject had a decrease in MED by 100 mj/cm2. Preliminary immunohistochemical analyses for thymine dimers and p21 expression demonstrate consistency with respect to the response to chloroquine in 82% of subjects. Decreased thymine dimers, decreased p21 levels and/or increased MED was observed in 55% of subjects. Increased dimers, increased p21 and/or no change in MED was observed in 27% of subjects. Discordant results were observed in 18% of subjects. Conclusions: Chloroquine can exert a measurable photoprotective response in human skin. It may also upregulate DNA damage repair pathways leading to decreased DNA damage after UV exposure. These results may lead to further studies regarding the role of chloroquine and similar drugs in the repair of DNA damage and the prevention of skin cancers. No significant financial relationships to disclose.
Chemotherapy with capecitabine plus temozolomide (CAP-TEM) in patients with advanced neuroendocrine neoplasms (NENs): an Italian multicenter retrospective analysis.
Authors: Francesca Spada, Lorenzo Antonuzzo, Riccardo Marconcini, Fabio Gelsomino, Caterina Fumagalli, Luca Messerini, Francesco Di Costanzo, Sergio Ricci, Gabriele Luppi, Anna Maria Frezza, Salvatore Galdy, Chiara ALESSANDRA Cella, Massimo Barberis, Nicola Fazio
Journal: Journal of Clinical Oncology (2015)

e15174 Background: Capecitabine (CAP) and temozolomide (TEM) have been reported to be active as first-line treatment in pancreatic neuroendocrine neoplasms (pNENs). We retrospectively evaluated activity and toxicity of CAP-TEM regimen in patients with advanced NENs with of different primary sites and correlation with clinical/biological factors. Methods: Patients received CAP (1500 mg/m2 b.d. day 1-14) and oral TEM (150-200 mg/m2 day 10-14) of each 28-day cycle. Disease control rate (DCR; PR+SD), time to progression (TTP) were calculated and toxicity recorded. MGMT methylation-status ( > 5% = responders) and TS-polymorphisms (2R/2R, 2R/3R = responders, 3R/3R = non-responders) in tumor-tissue/peripheral-blood were evaluated by pyrosequencing. Results: 58 consecutive patients treated since October 2009 were retrospectively reviewed (median age 58 years, 32 males, 47 non-functioning). The primary tumor sites included: 12 lung (21%), 32 pancreas (55%), 14 gastrointestinal tract and unknown (24%). Among lung primaries, 3 (25%) were typical and 9 (75%) atypical carcinoids (Travis' classification). Among the others, 5 (11%) were G1, 30 (65%) G2, 10 (22%) G3 (7