tbuckley/cabot-search huggingface dataset:
Randomized study comparing efficacy/toxicity of monotherapy trastuzumab followed by monotherapy docetaxel at progression, and combination trastuzumab/docetaxel as first-line chemotherapy in HER2-neu positive, metastatic breast cancer (MBC) (HERTAX study)
Authors: M. Bontenbal, C. Seynaeve, J. Stouthard, M. Bos, H. Braun, F. L. Erdkamp, G. van Deijk, P. Schmitz, I. Van der Stelt-Frissen, P. Hamberg, J. Klijn
Journal: Journal of Clinical Oncology (2008)

1014 Background: Treatment with trastuzumab and chemotherapy has improved the outcome of HER2-positive MBC. It is unknown what the outcome and toxicity is of monotherapy trastuzumab, followed by chemotherapy at progression, as compared to the combination of chemotherapy/trastuzumab. Methods: HER2-positive MBC pts., being eligible for first line chemotherapy were randomised between combination treatment docetaxel (TAX) (100 mg/m2, q3wks)/trastuzumab (HER) (loading dose 4mg/kg, whereafter weekly 2mg/kg) (arm A) or monotherapy HER, followed upon progression by TAX (similar doses as arm A) (arm B). Further in- /exclusion criteria were adjuvant non-taxoid chemotherapy allowed, previous HER treatment not; normal ejection fraction (EF), adequate liver/renal functions and bone marrow reserve. Primary endpoint was PFS, secondary endpoints: response rate (RR), overall survival (OS) and toxicities. Kaplan-Meier curve was tested by log-rank test, RR by Pearson χ2-test. Results: Of the 101 randomly selected patients, 2 were ineligible. Patient characteristics in arms A/B were not significantly (NS) different, being: median age 52/53 yrs (range 32–74); ER/PgR positive 47/47%; adjuvant chemo-/hormone therapy in 46/25% and 42/33%, respectively; prior hormone therapy for MBC in 37/36%. Objective RRs were 57% and 34% (p=0.03). PFS in arm A was 9.1 mo, while PFS on HER was 3.9 mo (p=0.0001), and after consecutive TAX 9.8 mo (arm B) (p=0.22). OS data is being analysed, and will be presented. Grade 3/4 neurosensory toxicity was only seen in arm A (6%). Other grade 3/4 toxicity was NS different (pulmonary complaints (9%), fatigue (8%), other ≤5%). Serious adverse events more frequently occurred in arm A (25/4), 2 toxic deaths in arm A, neutropenic fever 27/16%. LVEF decline >20% occurred in 16/15%. Conclusions: Monotherapy HER followed by monotherapy TAX yields a similar PFS as compared to combination therapy HER/TAX, and is associated with less grade 3/4 toxicity. Cardiac toxicity is NS different between both treatment modalities. Delaying cytotoxic therapy by using monotherapy HER may be a treatment option for particular patients. No significant financial relationships to disclose.
Morphologic Characteristics of Thymic Lymphomas Induced by &lt;italic&gt;N&lt;/italic&gt;-Nitroso-&lt;italic&gt;N&lt;/italic&gt;-propylurea in F344 Rats&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Y Suzuki, M Matsuyama, T Ogiu
Journal: JNCI Journal of the National Cancer Institute (1984)

Eighty-two thymic tumors induced by N-nitroso-N-propylurea in inbred F344/DuCrj rats were examined by light and electron microscopy. These tumors were diagnosed as malignant lymphomas and classified according to light microscopic features into three types: 1) lymphoblastic (57%), 2) large cell (32%), and 3) pleomorphic (11%). Electron microscopy revealed no epithelial cells in all 82 malignant lymphomas, except for 2, in which one sheet of epithelial cells was found under the capsule. This finding confirmed that all of these thymic tumors were malignant lymphomas, not thymomas. The tumors of the lymphoblastic and large cell types consisted of lymphoid cells with a few macrophages. Lymphoid cells of the lymphoblastic type were medium sized and contained a moderate amount of polyribosomes and a few clustered dense bodies; cells of the large cell type were much larger than those of the lymphoblastic type and contained many more polyribosomes and larger nucleoli. The tumors of the pleomorphic type consisted of lymphoid cells with severely infolded nuclei and interdigitating reticulum cells that were thought to be nonneoplastic in nature. No viral particle was found in these cells among the three types of thymic lymphomas.
Demographic difference in elderly patients with breast cancer
Authors: N. Mullai, Z. Lissanu
Journal: Journal of Clinical Oncology (2005)

872 Background: The elderly population in the United States is growing. There is enough evidence to suggest that elderly patients with cancer, who has good performance status, should be treated equally aggressively as younger patients. Based on these facts a retrospective analysis was done to look at the demographic difference in elderly patients with breast cancer. Methods: Records of 120 patients with breast cancer diagnosed and treated in rural Kentucky were analyzed for their demographics. Subsequently a comparison was done between patient groups of age younger than 70 years (Group-I) and age 70 years and older (Group-II). Results: Ninety-six patients were in Group-I and thirty-four patients were in Group-II. The oldest patient seen was 89 years of age. The important findings were as follows. An interesting observation was seen in six patients who were age 80 years or over. Four had stage II disease, four were hormone receptor negative, of which three had 2–3+ over expression of her2neu by immunohistochemistry. Conclusions:High number of elderly patients still had self /exam detected breast cancer, in spite of the recommendation for routine annual mammogram. Stage II breast cancer was 45%, similar to younger patients. Bilateral breast cancer even though uncommon was seen in 6%. Very elderly women (more than 80 years of age), showed bad prognostic factors like hormone negative status and her2neu over expression in more than 50% of the time. The above findings suggest that the trend is different in elderly population especially at age of 70 years and over. Further it supports the recent study from the University of Chicago that behavior of breast cancer is not more indolent in older patients compared to younger patients. Further attention and studies are recommended in this increasingly common very elderly sub-population to target treatments accordingly and aggressively. No significant financial relationships to disclose.
Fractionated total-body irradiation, etoposide, and cyclophosphamide plus autografting in Hodgkin's disease and non-Hodgkin's lymphoma.
Authors: S J Horning, R S Negrin, J C Chao, G D Long, R T Hoppe, K G Blume
Journal: Journal of Clinical Oncology (1994)

PURPOSE High-dose etoposide was incorporated into a regimen of fractionated total-body irradiation (FTBI) and high-dose cyclophosphamide before autologous transplant with the goal to enhance the antitumor effect of the myeloablative regimen in poor-risk lymphoid malignancies. PATIENTS AND METHODS Ninety-six patients, 24 with recurrent or refractory Hodgkin's disease and 72 with poor-risk non-Hodgkin's lymphoma (NHL), were treated on this study. Cytoreduction with conventional therapy was attempted before administration of the preparatory regimen. The preparatory regimen consisted of 12 Gy total-body irradiation administered in 10 1.2-Gy fractions on day -8 through day -5, etoposide 60 mg/kg on day -4, and cyclophosphamide 100 mg/kg on day -2. Patients with NHL received bone marrow purged with a panel of monoclonal antibodies and complement on day 0, while patients with Hodgkin's disease received peripheral-blood stem cells alone or with unmanipulated bone marrow. RESULTS The major morbidities of transplant were mucositis and skin toxicity. Eight patients (8.6%) died of regimen-related toxicities within 100 days of transplant. Engraftment was related to the rescue product; the median time to a neutrophil count more than 500/microL was 10 days for patients with Hodgkin's disease and 16 days for NHL patients. With a maximum follow-up duration of longer than 5 years, the 3-year actuarial survival rate is 57%. At 3 years, the actuarial freedom from progression (FFP) rate is 55% and the event-free survival rate is 47% for patients with Hodgkin's disease, while the respective figures for NHL patients are 60% and 53%. Among 32 patients with intermediate- and high-grade lymphoma transplanted subsequent to first relapse, 70% are free of lymphoma and 60% are event-free at &gt; or = 3 years. CONCLUSION The preparatory regimen consisting of FTBI, etoposide, and cyclophosphamide demonstrates relative efficacy in patients with Hodgkin's disease and NHL selected for high-dose therapy. Longer follow-up duration is needed to determine the rate of cure and to assess late complications. Major remaining challenges for high-dose therapy are a more inclusive strategy for all poor-risk patients and the need to reduce posttransplant relapses.
E7389, a novel anti-tubulin, in patients with refractory breast cancer
Authors: J. BlumL. Forero, M. K. Heiskala, N. Meneses, K. Chandrawansa, F. Fang, G. Shapiro, S. Z. Fields, S. Silberman, L. Vahdat
Journal: Journal of Clinical Oncology (2006)

653 Background: E7389 is a synthetic analog of halichondrin B, with a broad anti- proliferative activity against tumor cells. Methods: E7389 was evaluated in an open-label, single-arm Phase II trial as monotherapy for patients with refractory breast cancer (≥2 prior chemotherapy regimens, which must have included an anthracycline and a taxane). E7389 was administered as an IV bolus of 1.4 mg/m 2 on Days 1, 8, and 15 of a 28-day cycle (group 1), or on Days 1 and 8 of a 21-day cycle (group 2). The primary efficacy endpoint was ORR. Results: As of 9 December 2005, 88 patients had received treatment, 68 in group 1 and 20 in group 2. Median age was 55 yrs (range 36–84) and ECOG performance status 0–1. Sixty-six percent of the tumors were ductal carcinomas, 6% lobular, and 27% were unclassified. Sixty percent of the tumors were ER+, 47% PR+, and 17% Her2/neu 3+. The patients had received at least two previous regimens, with a median number of 5 (range 2–14). Forty-eight percent of the patients had also used hormonal therapy. Forty-nine patients in group 1 and 12 patients in group 2 had completed their 2 nd cycle of treatment, and twenty-one in group1 and 1 in group 2 their 4 th cycle. Safety: The major toxicity related to study drug was neutropenia. Among 73 patients with preliminary safety data available, two patients had Grade 3 febrile neutropenia, and 31 had Grade 3 or 4 neutropenia or leukopenia. The other Grade 3 toxicities encountered in more than two patients were dehydration (4 patients) and dyspnea (4 patients). Grade 3 peripheral neuropathy was reported in 2 patients. Efficacy: At the end of cycle four there were 10 (15.2%) confirmed partial responses (PRs) out of 66 evaluable patients in group 1, and 1 confirmed PR (5.6%) out of 18 evaluable patients in group 2. The median duration of confirmed responses was 113 days. Conclusions: Based on the safety and efficacy in this refractory breast cancer population, E7389 appears to be a therapy worthy of continued investigation in patients with heavily pretreated breast cancer. In order to comply with the current demand for individualized cancer care, bio-markers which would predict the sensitivity to E7389 are being searched in the tumor samples of the patients in the current and forthcoming studies. [Table: see text]
Association of Malignancy With Rapid Growth in Early Lesions Induced by Irradiation of Rat Skin&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J F McGregor
Journal: JNCI Journal of the National Cancer Institute (1979)

Epithelial lesions induced by irradiation of rat skin were studied to determine a) the relationship of malignancy to dose, b) the types of lesions and circumstances leading to overt malignancy, and c) the growth rates of lesions progressing to malignancy versus those of lesions remaining benign. High doses of radiation were shown to be associated with the production of epidermal cancers, the maximum yield being obtained at 6,400 rads. Conversely, a peak yield of noncancerous lesions was obtained at 1,600 rads. This association between malignancy and high dose was consistent for cancers evolving from warts, cysts, and chrnoic ulcers. Although the proportion of warts among the induced lesions was much higher than that of the cysts or chronic ulcers (76, 14, and 10%, respectively), the likelihood of warts becoming cancerous was substantially lower (14, 23, and 21%). The combined data for all doses showed that the latency period of the epidermal cancers was significantly (P = 0.015) shorter than that of the benign tumors. Rapid growth rates were observed for warts, cysts, and chronic ulcers progressing to overt cancer, and these did not overlap at any point on the growth scale with rates for benign tumors. This finding suggested that the potential for malignant development had been established early in the carcinogenic process, very likely at induction.
Ultrasound as the Primary Screening Test for Breast Cancer: Analysis From ACRIN 6666
Authors: Wendie A. Berg, Andriy I. Bandos, Ellen B. Mendelson, Daniel Lehrer, Roberta A. Jong, Etta D. Pisano
Journal: JNCI Journal of the National Cancer Institute (2015)

Mammography is not widely available in all countries, and breast cancer incidence is increasing. We considered performance characteristics using ultrasound (US) instead of mammography to screen for breast cancer.Two thousand eight hundred nine participants were enrolled at 20 sites in the United States, Canada, and Argentina in American College of Radiology Imaging 6666. Two thousand six hundred sixty-two participants completed three annual screens (7473 examinations) with US and film-screen (n = 4351) or digital (n = 3122) mammography and had biopsy or 12-month follow-up. Cancer detection, recall, and positive predictive values were determined. All statistical tests were two-sided.One hundred ten women had 111 breast cancer events: 89 (80.2%) invasive cancers, median size 12 mm. The number of US screens to detect one cancer was 129 (95% bootstrap confidence interval [CI] = 110 to 156), and for mammography 127 (95% CI = 109 to 152). Cancer detection was comparable for each of US and mammography at 58 of 111 (52.3%) vs 59 of 111 (53.2%, P = .90), with US-detected cancers more likely invasive (53/58, 91.4%, median size 12 mm, range = 2-40 mm), vs mammography at 41 of 59 (69.5%, median size 13 mm, range = 1-55 mm, P < .001). Invasive cancers detected by US were more frequently node-negative, 34 of 53 (64.2%) vs 18 of 41 (43.9%) by mammography (P = .003). For 4814 incidence screens (years 2 and 3), US had higher recall and biopsy rates and lower PPV of biopsy (PPV3) than mammography: The recall rate was 10.7% (n = 515) vs 9.4% (n = 453, P = .03), the biopsy rate was 5.5% (n = 266) vs 2.0% (n = 97, P < .001), and PPV3 was 11.7% (31/266) vs 38.1% (37/97, P < .001).Cancer detection rate with US is comparable with mammography, with a greater proportion of invasive and node-negative cancers among US detections. False positives are more common with US screening.
Eltrombopag and High-Dose Dexamethasone As First Line Treatment For ITP
Authors: David Gomez-Almaguer, Miguel Angel Herrera-Rojas, Andres Gomez-de Leon, Olga Graciela Cantú-Rodríguez, Cesar H Gutiérrez-Aguirre, Jose Carlos Jaime-Pérez, Luz C. Tarin-Arzaga, Guillermo J. Ruiz-Arguelles, Jesus Hernandez-Reyes
Journal: Blood (2013)
Proton ATPases and urinary acidification.
Authors: J G Kleinman
Journal: Journal of the American Society of Nephrology (1994)

Acidification of the urine is mediated by vectorial H+ transport from cells at a number of sites in the kidney. A proton ATPase has been described that appears to mediate a significant proportion of this H+ transport. In particular, in proximal tubule and collecting duct, there is evidence both for the presence of transporter protein and for H+ transport with features that have been identified with it. This review highlights some of the unresolved questions regarding this transporter, specifically, its distribution and relationship to the vacuolar pump present in endocytotic vesicles, how physiologic control is asserted, and its role in pathophysiology. The review discusses in greater detail the issue of whether the vacuolar H+ ATPase is responsible for all of the urinary acidification and concludes that it probably is not. Specifically, compelling evidence for acidification at sites in the kidney that appear to lack this transporter is presented. In addition, the evidence for the presence in the kidney of a gastric-type H(+)-K+ ATPase is also reviewed. The evidence appears to be strong for a K(+)-stimulated ATPase that is sensitive to omeprazole and SCH 28080, the prototypical H(+)-K+ ATPase inhibitors; however, uncertainties remain because of problems of transport inhibition specificity and discordant results of molecular biologic studies.
Clinical Impact of TP53 Gene Mutations in Diffuse Large B-Cell Lymphoma (DLBCL): An International DLBCL Rituxan-CHOP Consortium Program Study.
Authors: Ken H. Young, Nancy Patten, Sim Truong, Jens Eickhoff, Gabrielle L. Rocque, Jeffrey T. Malik, Yan Li, Kazunori Kanehira, Matthew Twohig, William M. Rehrauer, Michelle A. Waknitz, Brad S. Kahl, Michael B. Moller, Alexander Tzankov, Santiago M. Moreno, Miguel A. Piris, Carlo Visco, Karen Dybkaer, April Chiu, Attilio Orazi, Jeff C. Chang, Govind Bhagat, Jane N. Winter, Huan-You Wang, Cherie Dunphy, Stacey O'Neill, Eric D. Hsi, Xianfeng Zhao, Kristin Hunt, Weina Chen, Ronald S. Go, William W.L. Choi, Fan Zhou, Magdalena Czader, Yong Li, Suzanne Selvaggi, James S. Malter, Lin Wu
Journal: Blood (2009)
Differential Modulation Of cKIT Signaling By CD63 Dictates The Magnitude Of Response To Stem Cell Factor Of Erythroblasts From Adult Blood, Cord Blood and Polycythemia Vera
Authors: Ann Zeuner, Giulia Federici, Paola Contavalli, Emanuel F. Petricoin, Valentina Tirelli, Francesca Masiello, Gabriella Girelli, Giuliana Alimena, Agostino Tafuri, Giovanni Migliaccio, Anna Rita F Migliaccio
Journal: Blood (2013)
Degarelix: A gonadotropin-releasing hormone receptor (GnRH) blocker, tested in two one-year multicenter, randomized, dose-finding studies in prostate cancer patients
Authors: M. Gittelman, P. Pommerville, J. De La Rosette, B. E. Persson, J. K. Jensen, T. K. Olesen
Journal: Journal of Clinical Oncology (2006)

14516 Background: The GnRH receptor blocker degarelix has immediate onset of action in suppressing gonadotropins (LH and FSH), testosterone (T) and prostate specific antigen (PSA) and does not cause T surge. Its long-term efficacy and safety in different maintenance dosing regimens were evaluated in prostate cancer (CaP) patients. Methods: Degarelix was investigated in two multicenter, one-year studies in North America and Europe/South Africa. Degarelix initiation doses of 200 and 240 mg administered subcutaneously, followed by three maintenance doses (80, 120 and 160 mg). Therapeutic effect was assessed by measuring T and PSA levels. 314 patients (age 47–93, median 73 years) with histologically confirmed CaP, PSA ≥2 ng/mL received degarelix subcutaneously every 28 days. Median baseline T was 4.1 ng/mL and PSA was 20 ng/mL. 19% of patients had metastatic, 24% had locally advanced and 30% had localized CaP. 27% were M0/MX and not T-staged. Tumour grade was well differentiated (Gleason 2–4) in 13%, moderately differentiated (5–6) in 38%, and poorly differentiated (7–10) in 49% of the patients. Results: T levels ≤0.5 ng/mL were achieved in 92% of patients at Day 3 and 95% of patients at Day 28 among those treated with 240 mg (40 mg/mL) degarelix. From Day 28 until Day 364, 100% of patients receiving maintenance doses of 160 mg had T levels consistently ≤0.5 ng/mL. No evidence of T surge was detected. PSA decreased by 90% at 8 weeks after starting therapy, 94% at 12 weeks and 96% at 24 weeks. Twelve patients (6%) withdrew from the study due to adverse events, largely related to androgen deprivation. There were no cases of systemic allergic reactions. Conclusion: Degarelix treatment for one year resulted in fast, profound and sustained suppression of T (≤0.5 ng/mL) and fast, profound and sustained reduction of PSA levels. Degarelix was well tolerated without evidence of T surge or systemic allergic reactions. [Table: see text] [Table: see text]
Human Papillomavirus and Prognosis of Invasive Cervical Cancer: A Population-Based Study
Authors: Stephen M. Schwartz, Janet R. Daling, Katherine A. Shera, Margaret M. Madeleine, Barbara McKnight, Denise A. Galloway, Peggy L. Porter, James K. McDougall
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To determine the association between human papillomavirus (HPV) type and prognosis of patients with invasive cervical carcinoma. PATIENTS AND METHODS: Patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IB to IV cervical cancer between 1986 and 1997 while residents of three Washington State counties were included (n = 399). HPV typing was performed on paraffin-embedded tumor tissue using polymerase chain reaction methods. Patients were observed for a median of 50.8 months. Total mortality (TM) and cervical cancer–specific mortality (CCSM) were determined. Hazards ratios (HR) adjusted for age, stage, and histologic type were estimated using multivariable models. RESULTS: Eighty-six patients had HPV 18–related tumors and 210 patients had HPV 16–related tumors. Cumulative TM among patients with HPV 18–related tumors and among patients with HPV 16–related tumors were 33.7% and 27.6%, respectively; cumulative CCSM in these two groups were 26.7% and 18.1%, respectively. Compared with patients with HPV 16–related cancers, patients with HPV 18–related cancers were at increased risk for TM (HR TM , 2.2; 95% confidence interval [CI], 1.3 to 3.6) and CCSM (HR CCSM , 2.5; 95% CI, 1.4 to 4.4). The HPV18 associations were strongest for patients with FIGO stage IB or IIA disease (HR TM , 3.1; 95% CI, 2.3 to 4.2; and HR CCSM , 5.8; 95% CI, 3.9 to 8.7), whereas no associations were observed among patients with FIGO stage IIB to IV disease. Virtually identical associations were found in the subset of patients with squamous cell carcinoma (n = 219). CONCLUSION: HPV 18–related cervical carcinomas, particularly those diagnosed at an early stage, are associated with a poor prognosis. Elucidating the mechanism or mechanisms underlying this association could lead to new treatment approaches for patients with invasive cervical carcinoma.