tbuckley/cabot-search huggingface dataset:
Clonogenicity and Experimental Metastatic Potential of Spontaneous Mouse Mammary Neoplasms&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: J E Price
Journal: JNCI Journal of the National Cancer Institute (1986)

Spontaneous primary mammary tumors of C3H-Avy mice differ in metastatic colonization potential, some producing many lung deposits (high-colonization potential) and others producing few or none (low-colonization potential) after iv inoculation of cells. The degree of metastasis from undisturbed neoplasms also varies from tumor to tumor. This study examined whether these differences between tumors could be accounted for by differences in clonogenic or stem cell content. Tests for clonogenic cells were: growth in 0.3% agarose and limiting dilution assays. Mammary tumor cells of known colonization potential were inoculated iv at serially reduced doses, and the relationship between number of cells injected and number of lung deposits formed was determined. Parallel in vitro dose-response assays in 0.3% agarose were performed with the use of cells from the same primary tumors. Colony-forming efficiency in 0.3% agarose cultures varied between individual primary mammary tumors and was positively associated with experimental metastatic potential, suggesting that the stem or clonogenic cell content of primary tumors is one of the important determinants of the metastatic phenotype.
Risk management and eligibility criteria for QTc assessment in patients with advanced cancer
Authors: N. Sarapa, X. Huang, M. Varterasian, H. Fingert
Journal: Journal of Clinical Oncology (2005)

3047 Background: Emerging regulatory and industry practices (ICH E14, 2004) require the potential for QTc interval prolongation to be characterized in a 'Thorough QT' (TQT) study with eligibility restricted based on screening QTc criteria (<430 ms in men, <450 ms in women) derived from non-oncology experience. For patients with advanced cancer who volunteer for Phase 1–2 clinical studies of promising new agents, risk-benefit implications of these and other TQT components have not been well defined. Methods: We surveyed baseline QTc interval in 160 adult patients with advanced malignancy enrolled into two Phase 2 trials with an experimental anticancer agent [97 GIST, 63 renal cell carcinoma; mean age 55.7 years (range 24, 87)]. QTc was measured by the ECG recorder's automated algorithm on single 12-lead ECG obtained prior to treatment. Results: No significant differences in mean or median QTc were observed for patients aged <65 versus >=65 years. Distribution by gender-specific QTc risk categories showed that 94 men (87.9%) and 49 women (92.5%) had normal QTc (<430 and <450 ms, respectively). Eleven men (10.3%) and 4 women (7.6%) had borderline QTc (430–450 and 450–470 ms, respectively), while 2 men (1.9%) and no women had prolonged QTc (>450 and >470 ms, respectively). No QTc was >500 ms (CTCAE Grade 3). Overall, 17 of 160 patients (10.6%) had baseline QTc above the upper limits of normal. Conclusions: These data are consistent with anecdotal reports that cancer patients may have longer QTc than other segments of the population. Over 10% of our patients would have been excluded from treatment with a promising anticancer agent if eligibility criteria from TQT studies in non-oncology populations were applied. Given risk-benefit considerations and expectations for access to new agents in clinical trials, our data support alternative approaches to eligibility criteria and risk management in studies designed to evaluate QTc prolongation in patients with advanced cancer. No significant financial relationships to disclose.
Detection of discordant HER2 status by FISH in circulating tumor cells and disseminated tumor cells in early-stage breast cancer using a microfluidic-based cell enrichment and extraction platform (OncoCEE).
Authors: Savitri Krishnamurthy, Farideh Z. Bischoff, Julie Ann Mayer, Henry Mark Kuerer, Ashutosh Lodhi, Anirban Bhattacharyya, Carolyn S. Hall, Karina Wong, Tam Pham, Tony J Pircher, Anthony Lucci
Journal: Journal of Clinical Oncology (2012)

TPS10631 Background: Evaluation of HER2 in circulating (CTCs) and disseminated (DTC) tumor cells may aid therapy in breast cancer. We report here the discordance in HER2 status in CTCs and DTCs in early stage breast cancer by fluorescence in situ hybridization (FISH) using a microfluidic cell platform (OncoCEE). Methods: Blood (10ml) and BM (1-2ml) from patients with Stage T1 and T2 breast cancer was collected in OncoCEE-Sure collection tubes. Mononuclear cells were recovered using a Percoll density gradient method, incubated with a mixture of 10 primary capture antibodies (Abs), and introduced into streptavidin coated OncoCEE microchannels for tumor cell capture. For blood samples, captured cells were stained with anti cytokeratin (CK) and CD45 Abs for CTC enumeration followed by FISH using probes specific to centromere 17 and HER2. For BM samples, captured cells were subjected to HER2 FISH analysis. The ratio of HER2:CEP17&gt;2.0 in any CK+/ CD45- and CK-/CD45- cell was regarded as positive for HER2. Results: Blood and BM from 68 patients (68 Blood, 54 BM; 54 matched blood and BM) with stage T1N0 (41), T1N1 (6), T2N0 (11), T2N1(2), T2N2 (1), T2N3 (2) with HER2+ (n=7) and HER2- (n=61) breast cancers were studied. The 7 patients with HER2 + primary tumor had HER2+ DTCs in 3/7 (43 %) and HER2 + CTCs in 1/6 (17 %) patients. HER2 + DTCs and HER2 + CTCs occurred in 10/47 (21%) and in 4/57 (7%) patients with HER2- primary breast tumors. The discordance of HER2 status was observed in 14% in CTCs and in 22% in DTCs. Conclusion: 1. The cell enrichment and extraction microfluidic platform (OncoCEE) provides a sensitive approach for evaluation of HER2 in CTCs and DTCs. 2. CTCs and DTCs acquired HER2 gene amplification in 21% and 7% of patients with HER2 negative early stage primary breast cancer. 3. CTCs and DTCs lost HER2 gene amplified status in 57% and 83% of patients with HER2 positive early stage primary breast cancer. 4. The clinical significance of alterations in HER2 status among CTCs and DTCs in early stage breast cancer needs further investigation.
Tamoxifen dosage and bioequivalence: a correction.
Authors: A M Mondzac
Journal: Journal of Clinical Oncology (1994)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1994.12.9.1993 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8083720 Tamoxifen dosage and bioequivalence: a correction. A M MondzacxA M MondzacSearch for articles by this author https://doi.org/10.1200/JCO.1994.12.9.1993 PDF "Tamoxifen dosage and bioequivalence: a correction.." Journal of Clinical Oncology, 12(9), pp. 1993–1994© 1994 by American Society of Clinical Oncology
Cerebral and muscle oxygenation during intermittent hypoxia in healthy human
Authors: Samuel Verges, Arthur Peyrard, Jean-Louis Pépin, Thomas Rupp, Patrick Levy
Journal: European Respiratory Journal (2014)

Sleep apnoea is characterized by episodes of intermittent hypoxia (IH) known to have critical cardiovascular consequences. IH is defined based on changes in arterial oxygen saturation (SpO 2 ), but the impact of intermittent hypoxemia on human tissue oxygenation remains unknown. Some data in animal models suggest differences between arterial and tissue oxygenation as well as between organs during IH. We hypothesised that the brain would exhibit greater oxygenation changes than the muscle during IH. 10 healthy subjects were exposed, awake, for 45 min to IH (FiO 2 =11%, 20-s oxygen administration at 2 L/min every 2 min). Earlobe SpO 2 , prefrontal and brachial biceps near infrared spectroscopy signals (tissue saturation index – TSI, oxy/deoxy- and total-haemoglobin concentration changes), ventilation and blood pressure were continuously recorded. SpO 2  oscillated by 9±3% on average (range 88%-97%) during IH. Prefrontal TSI during IH (mean 65±8%, max 67±9%, min 64±7%) was significantly reduced compared to normoxic baseline (71±7%). Muscle TSI did not change significantly during IH compared to normoxic baseline. The brain showed greater 2-min oxy/deoxy-haemoglobin oscillations compared to the muscle (Fig 1). This study shows for the first time in human tissue-specific sensitivity to IH and major impact of systemic IH on cerebral but not muscle oxygenation.  Fig 1. Arterial, muscle and brain mean oxygenation changes over 2-min IH cycles.
Inhibition by Retinoic Acid of Murine Retrovirus-Induced Cellular Transformation and Tumor Formation&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: N A Giese, K E Neary, N Levine, T J Lindell, J J Duffy
Journal: JNCI Journal of the National Cancer Institute (1985)

The effect of all-trans-retinoic acid (RA) on cellular transformation and on tumorigenicity of retrovirally transformed cells was investigated. RA treatment of NRK and NIH/3T3 cells transformed by BALB/c murine sarcoma virus (MuSV), Kirsten murine sarcoma virus (K-MuSV), and simian sarcoma virus resulted in a significant reduction in anchorage-dependent growth of only K-MuSV-transformed NRK cells. A 62% reduction in cell number was observed at 10(-5) M RA. In contrast, anchorage-independent growth induced by each of the viruses tested was suppressed by RA. Balb/cMSV3T3 cells showed the greatest level of sensitivity with a significant reduction in anchorage-independent growth occurring at 10(-9) M RA. The level of cytoplasmic retinoic acid-binding protein (CRABP) was determined in both parent and transformed cell lines. CRABP was present at a high level in all 3T3 cell types but was absent in all NRK cell lines. For testing the antineoplastic activity of RA in vivo, Balb/cMSV3T3 cells were injected intradermally into nude mice. Subsequent treatment of the tumor sites of these animals by topical application of RA resulted in a significant reduction in both tumor incidence and tumor size, confirming the in vitro results. Analysis of the level of v-onc mRNA revealed that inhibition of retroviral transformation by RA was not due to a decrease in transcription of the v-onc genes.
Chemotherapy of metastatic seminoma: the Southeastern Cancer Study Group experience.
Authors: P J Loehrer, R Birch, S D Williams, F A Greco, L H Einhorn
Journal: Journal of Clinical Oncology (1987)

From 1978 to 1984, 62 patients with advanced seminoma of testicular or extragonadal origin were entered on two consecutive Southeastern Cancer Study Group (SECSG) protocols. All patients had progressive disease and were stratified according to tumor burden. Randomization on SEG 78-GU240 was cisplatin, vinblastine, and bleomycin (PVB), with or without doxorubicin; on SEG 81-GU332, randomization was to PVB or cisplatin, etoposide (VP-16), and bleomycin (PVP16B). Dosages of etoposide, vinblastine, and doxorubicin were decreased by 25% in patients who had received prior radiotherapy. Thirty patients (55%) had received prior chest and/or abdominal radiotherapy. Overall, 41 of 60 evaluable patients (68%) achieved a complete remission (CR) and 37 patients are alive and free of disease. CR was obtained in 13 of 15 patients (87%) with minimal disease, 13 of 16 (81%) with moderate disease, and 15 of 29 (52%) with advanced disease. Patients with no prior radiotherapy or limited-field (chest or abdomen) radiotherapy were more likely to achieve CR than those with prior chest and abdominal radiotherapy (75% v. 42%). Using univariate analysis, the extent of disease is the only significant prognostic factor, whereas both extent of disease and extent of prior radiotherapy are significant in a multivariate analysis. This study confirms the chemosensitivity of metastatic seminoma in a cooperative group setting and defines prognostic factors useful for comparison of other chemotherapeutic trials in seminoma.
The Epidemic of Infantile Paralysis
Journal: JAMA (2016)

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Risk factors of recurrence after adjuvant concurrent chemoradiotherapy following radical hysterectomy in high-risk patients with cervical cancer
Authors: H. Chung, J. Kim, N. Park, Y. Song, S. Kang, H. Lee
Journal: Journal of Clinical Oncology (2008)

16543 Background: This study was undertaken to evaluate the risk factors of recurrence after postoperative concurrent chemoradiotherapy (CCRT) and to investigate the survival rates after adjuvant CCRT in high-risk early cervical cancer (stages IA2, IB, IIA) patients who were treated by radical hysterectomy and pelvic lymphadenectomy. Methods: From January 2000 to December 2006, we retrospectively reviewed the medical records of 311 patients who had undergone radical hysterectomy with pelvic lymphadenectomy for early cervical cancer (stages IA2, IB, IIA). CCRT was performed in 107 patients with high-risk factors such as positive pelvic lymph nodes, parametrial involvement, or positive surgical margins. Adjuvant chemotherapy consisted of platinum-based combination chemotherapy for three cycles every 3 weeks or beginning 2–3 weeks after surgery. Pelvic radiotherapy was started concurrently at the first cycle of chemotherapy. We analyzed the factors of recurrence and survival rates of the patients. Results: A total of 107 patients with median age of 55 years (range 33–77) were eligible for analysis. Squamous cell carcinoma was the most common (77.6%) histologic type, and over half (57.9%) the patients were FIGO stage IB1. Lymph node metastasis, positive resection margins, and full cervical stromal invasion were present in 42.1%, 29.9%, and 59.8% respectively. The presence of endometrial involvement of tumor was associated with poor progression-free survival (OR 3.645, 95% CI, 1.918, 6.926, p<0.001) while not associated with overall survival difference. Conclusions: This study confirms that endometrial involvement is associated with tumor recurrence after adjuvant CCRT in stages IA2-IIB cervical cancer patients with high-risk factors. No significant financial relationships to disclose.
Abstract P181: Cardiac Structure is Associated with Obesity and Blood Pressure But Not Inflammation
Authors: Robert A Palermo, Samuel S Gidding, Stehpanie S DeLoach, Scott W Keith, Bonita Falkner
Journal: Circulation (2012)

Purpose: The aim of this study was to identify risk factors associated with cardiac structure in a cohort of African American adolescents oversampled for obesity and high blood pressure (BP). Additional associations of cardiac structure with a pro-inflammatory adipokine profile (low adiponectin, elevated IL6, PAI-1 and CRP) were sought. Methods: A cross-sectional study was conducted using a two-by-two factorial design with four groups of African American adolescents based on BP (prehypertension or stage 1 hypertension=high BP) and body mass index (BMI &gt; 95% =obese) designation. Measurements included: echocardiogram, anthropomorphics, BP (on 3 separate occasions), high sensitivity CRP and plasma adipokines (adiponectin, IL6, PAI-1). Standardized echocardiogram measurements were used to obtain left ventricular mass index (LVMI, g/m 2.7 ) and left atrial diameter index (LADI, mm/m 2 ). Ordinary least-squares regression with model selection by Mallow's Cp was used to determine if pro-inflammatory adipokine profile predicted LV mass and LA diameter in models including age, gender, BMI z-score, and systolic BP. Results: Data on 251 African American adolescents, ages 13-19, were analyzed. BMI-z score was strongly associated with a pro-inflammatory adipokine profile whereas high BP was not. Variation in LADI was significantly associated with BMI (β=0.12, p&lt;0.01) and female gender (β=0.08, p=0.04). LVMI variation was significantly associated with BMI (β=3.53, p&lt;0.01), age (β=0.71, p&lt;0.01), female gender (β=-4.32, p&lt;0.01), and systolic BP (β=0.10, p=0.03). Though significant in univariate models, inflammatory markers were not significantly associated with LADI or LVMI after BMI adjustment. Conclusions: In African American adolescents, BMI is an important determinant of LADI and LVMI. Obesity is associated with a pro-inflammatory adipokine profile but LADI and LVMI are not. Table. Regression modeling results after variable selection by Mallow C p : Left Atrium Diameter Index and Left Ventricular Mass Index (N = 251) LADI LVMI Estimate (95% CL) p-value Estimate (95% CL) p-value Age (yr) 0.00063 (-0.021, 0.023) 0.955 0.71 ( 0.18, 1.24) 0.009 Gender (F) 0.08 ( 0.01, 0.16) 0.036 −4.32 (-6.13,-2.51) &lt;.001 BMI z-score 0.12 ( 0.08, 0.16) &lt;.001 3.53 ( 2.66, 4.40) &lt;.001 Systolic BP 0.0019 (-0.0017, 0.0055) 0.306 0.0952 ( 0.0085, 0.1819) 0.032
Anxiety levels in patients randomized to adjuvant therapy versus observation for early breast cancer.
Authors: B R Cassileth, M W Knuiman, M D Abeloff, G Falkson, E Z Ezdinli, C R Mehta
Journal: Journal of Clinical Oncology (1986)

We studied anxiety levels in 68 patients who had been randomized to adjuvant chemotherapy v observation on two Eastern Cooperative Oncology Group (ECOG) protocols. All subjects were women who had undergone total or modified radical mastectomy for breast cancer. Immediately before breast protocol randomization and again 3, 6, and 12 months later, patients completed two self-report measures: the State-Trait Anxiety Inventory and the SCL-90. There were no consistent trends in anxiety levels over time. At each test point, patients under observation displayed higher anxiety scores than did patients receiving adjuvant therapy, but these differences failed to attain statistical significance. Power calculations indicate that these results rule out the possibility of major differences in anxiety levels among patients randomized to observation v adjuvant therapy, but a larger patient sample is required before a definitive statement can be made about smaller differences.
Incidence and time course of bleeding after long term amenorrhea following breast cancer treatment: A prospective study
Authors: P. Sukumvanich, J. A. Petrek, M. J. Naughton, D. Case
Journal: Journal of Clinical Oncology (2005)

575 Background: A gynecological work-up for pathological causes of vaginal bleeding is commenced if a woman has had no menstrual period for 12 months. In lieu of clinical studies this recommendation stands even for young women with amenorrhea due to chemotherapy. Methods: 595 US women ages 20–45 were accrued from January 1998 to July 2002 within 8 months of diagnosis with Stages I-III breast cancer (median follow-up 45 months). Daily bleeding and spotting records were obtained throughout the study. Baseline extensive clinical, demographic, and treatment data (with each drug, dose and date) were obtained and followup every 6 months. Episodes of vaginal spotting were excluded from analysis. Kaplan-Meier analysis was used to estimate the incidence of at least one bleeding episode after prolonged amenorrhea. Results: The median age of the patients was 39.5 years old (range 20–45 years old). 29% of the patients became amennorheic for 12 months after chemotherapy with no significant difference seen among the 3 regimens (31%, 20% and 29% in the AC (doxorubicin, cyclophosphamide), ACT (doxorubicin, cyclophosphamide, taxol) and CMF (cyclophosphamide, methotrexate, 5-FU) respectively). 42% of the AC group bled within the following 4 years as compared to 33% and 16% in the ACT and CMF treated patients respectively. 22% of the patients experienced an initial two-year period of amenorrhea; only 9% of these women bled in the ensuing 3 years. Younger women were more likely to bleed after prolonged amenorrhea when analyzed with a repeated measures logistic regression (p = .03) and Cox proportional hazards model (p = .03). Conclusions: A considerable portion of patients treated with chemotherapy have at least one bleeding episode despite an initial 12 months of amenorrhea. Given this high proportion, a negative gynecological work-up for uterine pathology may not be unexpected especially in younger women and those treated with AC and ACT. This prospective study is the first to provide information that bleeding is common after chemo-induced amenorrhea (29%). More research is necessary to make recommendations pertaining to the appropriate work-up of vaginal bleeding after chemo-induced amenorrhea. No significant financial relationships to disclose.
The effects of VEGF and VEGFR-2 on survival in patients with gastric cancer
Authors: F. Aydin, F. Ozdemir, R. Akdogan, A. Reis, H. Kavgaci
Journal: Journal of Clinical Oncology (2005)

9651 Background: Prognostic criteria of the patients with gastric cancer are of critical importance in their management and follow-up. Angiogenesis is essential for the growth and metastasis of solid tumors. Tumor angiogenesis is a multi-step interactive process; and vascular endothelial growth factor (VEGF) and its receptors have a major role in tumor angiogenesis. Thus, we investigated the effects of VEGF and VEGF receptor-2 (VEGFR-2, KDR) on survival in patients with gastric cancer. Methods: We analyzed 51 patients who had undergone total or subtotal gastric resection. The patients were divided into two subgroups according to their VEGF and VEGFR-2 (KDR) expression in resected specimens. Results: There was no significant difference between sex, surgical method, lymph node metastasis, serosal invasion, hematogenous metastasis, chemotherapy status of the two subgroups. Mean follow-up time was 24.22±15.38 months. We found the survival rates of the patients with VEGF positive tumors to be significantly shorter than those of the patients with VEGF negative tumors. There was no significant difference between the survival rates of VEGFR-2 (KDR) positive and negative patients. Conclusions: It was established that the presence of VEGF expression was significantly associated with the short survival rates in patients with gastric cancer. Analysis of VEGF expression in resected specimens may provide additional guidance in determining the prognosis of such patients. If more extensive studies confirm the significance of VEGF and its receptors in gastric cancer, new therapeutic approaches targeting VEGF and its receptors may be considered in gastric cancer management. No significant financial relationships to disclose.