tbuckley/cabot-search huggingface dataset:
Weekly paclitaxel/estramustine phosphate plus carboplatin administered either weekly or every 4 weeks in the treatment of hormone refractory prostate cancer (HRPC): A randomized phase II trial of the Minnie Pearl Cancer Research Network
Authors: A. A. Meluch, F. A. Greco, H. A. Burris, J. B. Erland, R. A. Khan, G. I. Rodriguez, J. G. Gandhi, J. D. Hainsworth
Journal: Journal of Clinical Oncology (2004)

4659 Background: Treatment with combination antimicrotubule agents improves the response rate in patients (pts) with HRPC. Carboplatin, when added to paclitaxel/estramustine, is also well tolerated and active. However, the optimal scheduling of carboplatin is uncertain. In this randomized phase II trial, we compare the toxicity and efficacy of carboplatin administered weekly versus monthly, along with weekly paclitaxel/estramustine. Methods: Pts with metastatic HRPC and ≤ 1 previous chemotherapy regimen were eligible. Additional eligibility criteria: ECOG PS 0–2; adequate organ function; informed consent. All pts received paclitaxel (90mg/m2 IV days 1, 8, 15) and estramustine (140mg PO tid days 1–3, 8–10, 15–17). Pts were randomized to receive carboplatin either weekly (AUC 2.0 days 1, 8, 15) or monthly (AUC 6.0 day 1). Courses were repeated every 28 days. Pts were evaluated for response after 2 courses; responders continued treatment for 6 courses. Results: Between 8/00 and 7/03, 86 pts were randomized; 81 pts are currently evaluable, with median follow-up of 24 months. The 2 groups were well balanced in terms of PS, age, sites of metastases, previous treatment. Both groups received a median 6 courses of treatment. Response rates and PFS were similar with the 2 regimens (see table). Both regimens were well tolerated. Grade 3/4 neutropenia occurred in 7% of pts, with only 2 episodes of neutropenia/fever. Grade 3/4 nonhematologic toxicities occurred in < 10%. There were no significant differences in any toxicity between the 2 treatments. Conclusions: The combination of weekly paclitaxel, estramustine, and carboplatin is effective and well tolerated for pts with HRPC. The scheduling of carboplatin did not affect response rate or toxicity in this group of patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis Bristol-Myers Squibb
Success rates in psychiatry and neurology certification examinations
Authors: M Greenblatt, J Carew, C M Pierce
Journal: American Journal of Psychiatry (1977)

The authors traced the progress of a sample of 200 psychiatrists and 150 neurologists on the ABPN examination. Overall success rates were high-64% of psychiatrists and 75% of neurologists became Board-certified. Performance on the written exam was a significant predictor of outcome for both groups-88% of psychiatrists and 94% of neurologists who passed Part I on their first try eventually obtained certification. Given the criticism that has been directed toward the oral exam, it was interesting that only 10% of psychiatrists and 5% of neurologists failed to become diplomates because of difficulties with Part II. Future research will deal with the validity and reliability of the oral exam.
Amyloid imaging using fluorine-19 magnetic resonance imaging (19F-MRI)
Authors: Ikuo Tooyama, Daijiro Yanagisawa, Hiroyasu Taguchi, Tomoko Kato, Koichi Hirao, Nobuaki Shirai, Takayuki Sogabe, Nor Faeizah Ibrahim, Toshiro Inubushi, Shigehiro Morikawa
Journal: Ageing Research Reviews (2016)
Bicalutamide Monotherapy Versus Flutamide Plus Goserelin in Prostate Cancer Patients: Results of an Italian Prostate Cancer Project Study
Authors: Francesco Boccardo, Alessandra Rubagotti, Mario Barichello, Michele Battaglia, Giorgio Carmignani, Giancarlo Comeri, Giario Conti, Giorgio Cruciani, Sandro Dammino, Umberto Delliponti, Pasquale Ditonno, Valentino Ferraris, Sergio Lilliu, Franco Montefiore, Filippo Portoghese, Giovanni Spano
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To compare the efficacy of bicalutamide monotherapy to maximal androgen blockade (MAB) in the treatment of advanced prostatic cancer. PATIENTS AND METHODS: Previously untreated patients with histologically proven stage C or D disease (American Urological Association Staging System) were randomly allocated to receive either bicalutamide or MAB. After disease progression, patients treated with bicalutamide were assigned to castration. The primary end point for this trial was overall survival. Secondary end points included response to treatment, disease progression, treatment safety, quality-of-life (QOL), and sexual function. RESULTS: A total of 108 patients received bicalutamide and 112 received MAB. There was no difference in the percentage of patients whose prostate-specific antigen returned to normal levels. At the time of the present analysis (median follow-up time, 38 months; range, 1 to 60 months), 129 patients progressed and 89 died. There was no difference in the duration of either progression-free survival or overall survival. However, a survival trend favored bicalutamide in stage C disease but MAB in stage D disease. Overall and subgroup trends were confirmed by multivariate analysis. Serious adverse events and treatment discontinuations were more common in patients receiving MAB (P = .08 and P = .04, respectively). Fewer patients in the bicalutamide group complained of loss of libido (P = .01) and of erectile dysfunction (P = .002). Significant trends favored bicalutamide-treated patients also with respect to their QOL, namely relative to social functioning, vitality, emotional well-being, and physical capacity. CONCLUSION: Bicalutamide monotherapy yielded comparable results relative to standard treatment with MAB, induced fewer side effects, and produced a better QOL.
Trimodality treatment (TMT) for locally advanced esophageal cancer in Pakistan; Analysis of prognostic factors influencing survival
Authors: A. A. Syed, A. Jamshed, B. Muhammad, R. Azhar, M. A. Yusuf, Y. I. Khan, Q. Ahmed, K. Shehzad, K. Rehman, Z. Faruqui
Journal: Journal of Clinical Oncology (2007)

15185 Background: The prognosis of patients with locally advanced esophageal cancer is poor. TMT for locally advanced esophageal cancer is being utilized with increasing frequency. In this study, we investigate the prognostic factors influencing survival in patients with locally advanced esophageal cancer following TMT. Methods: The study included 22 patients with esophageal carcinoma treated between January 2003 and December 2005 at Shaukat Khanum Memorial Hospital and Research Centre. Median age was 49 years (range 26 - 68). There were 15 (68%) males and 7 (32%) females. All patients had EGD with biopsy and CT chest. Twelve (54.5%) had squamous cell carcinoma and 10 (45.5%) patients had adenocarcinoma. Five patients (23%) had tumour in the middle third and 17 (77%) had lower/gastroesophageal lesions. Preoperative radiation consisted of 50.4 Gy / 28 fractions with concomitant chemotherapy day 1 and 29 (Cisplatin 75 mg/m 2 day 1 and infusional 5FU 1000 mg/m 2 day 1–5). Esophagectomy was done at 6 - 12 weeks following chemoradiation. The pathologic down-staging was evaluated by the 5-score tumor regression grade (TRG) of Mandard. Results: Post TMT pathologic TNM stage was; Stage 0 in 8 pts (36%), stage II in 5 pts (23%) and stage III in 9 pts (41%). 13 (59%) pts had R0 and 9 (41%) pts had R1 resection. The 4-year disease free survival was 29% with a median survival of 19 months. The number of patients with TRG score 1, 2, 3, 4 and 5 were 7 (32%), 4 (18%), 5 (23%), 2 (9%) and 4 (18%) respectively. Tumor regression grade 1–2 (p=.0016) and negative circumferential margins &gt;2 mm (p=.0019) had a positive influence on DFS. Age (&lt; 50 vs ≥ 50 years), sex, hemoglobin at presentation (≤ 12 vs &gt; 12 gm/dl), tumor site (middle vs lower/GE junction), pathological nodal status (node positive vs node negative) and histological subtype (squamous cell vs adenocarcinoma) did not influence survival (p= 0.92, p= 0.82, p= 0.69, p= 0.79, p= 0.41 and p= 0.32 respectively). Conclusions: TMT results in prolonged disease free survival in patients with complete response or microscopic residual foci (TRG 1–2). Positive or circumferential margins &lt;2mm is associated with poor prognosis. No significant financial relationships to disclose.
Abstract 19114: Ultrasound-targeted Destruction of Nucleic-acid Loaded Microbubbles Enhances Payload Delivery at the Treatment Site: A Quantitative Comparison of Delivery Strategies
Authors: Andrew R Carson, Jonathan A Kopechek, Xucai Chen, Charles F McTiernan, Linda Lavery, Bima Hasjim, Malabika Sen, Jennifer R Grandis, Flordeliza S Villanueva
Journal: Circulation (2014)

Background:  Custom designed microbubbles (MB) can carry therapeutic agents to target tissues. It has been posited, but not proven, that when MB are exposed to ultrasound (US) directed at the target, therapeutic agents are locally released and concentrated at the target site. Accordingly, we studied local delivery using MB and US, utilizing STAT3 transcription factor decoy as a model therapeutic, which has previously been shown to suppress tumor growth by inhibiting STAT3 signaling.   Methods:  Cationic MB loaded with P 32  labeled STAT3 decoy (8 μg per 1х10 9  MBs) were intravenously infused into mice bearing squamous cell carcinoma (n=6). US was delivered to the tumor with a clinical scanner (MI setting 1.6; 4 frames/burst, burst interval 2 s, f=1.3MHz) during a 20 min MB infusion and 5 min thereafter. Tumors were harvested at 5 min or 8 hrs after therapy and analyzed for decoy content. Intact decoy was isolated by ethanol precipitation, quantified by scintillation counting, and expressed as percent input signal/gram tissue. Controls (no US) received decoy alone or decoy-loaded MB (decoy-MB).   Results:  5 min after treatment, total decoy in the tumor was higher in the decoy-only group (0.74±0.20%/g) compared to decoy-MB (0.24±0.08%/g) or decoy-MB+US groups (0.46±0.15%/g; p intact  decoy were 2-3 fold higher in decoy-MB+US treated mice (0.26±0.16%/g) compared to decoy-MB (0.09±0.08%/g) or decoy alone (0.09±0.02%/g).   Conclusions:  To our knowledge, this is the first comparative quantification of molecular therapeutic delivery to target tissue resulting from directed US-induced destruction of circulating MBs. Decoy-MB + US treatment enhanced transcription factor decoy deposition in target tissue at 8 hours compared to control groups subjected to non-US targeted delivery strategies. These data substantiate the rationale for targeted therapeutics using US and loaded MBs.
A phase I study evaluating two dosing schedules of bortezomib (Bor) with rituximab (R), cyclophosphamide (C) and prednisone (P) in patients with relapsed/refractory indolent and mantle cell lymphomas
Authors: J. F. Gerecitano, C. Portlock, P. Hamlin, C. Moskowitz, A. Noy, D. J. Straus, A. D. Zelenetz, P. Schulman, O. Dumitrescu, O. A. O’Connor
Journal: Journal of Clinical Oncology (2008)

8512 Background: To determine the safety and efficacy of Bor with modified R-CVP (omitting vincristine). Rationale: Vincristine has marginal activity in indolent lymphomas, and preclinical data suggests that Bor dosed after chemotherapy may be synergistic and overcome drug resistance. Methods: In this phase I trial, Bor (see doses below) and C (750 mg/m2 or 1000 mg/m2) were alternately escalated. R (375 mg/m2) and C were dosed on day one, and P (100 mg daily) on days 2–6. In schedule 1, Bor was given on days 2 and 8, with doses escalated from 1.3 to 1.8 mg/m2. In schedule 2, Bor was given on days 2, 5, 9 and 12 with doses escalated from 1.1 to 1.5 mg/m2. Patients with PR or SD (modified Cheson (1999) criteria) after 4 cycles received 4 further cycles, those with CR got 2 further cycles. Toxicity was assessed using NCI-CTC, v. 3.0. DLT was defined as: grade ≥ 3 nonhematologic toxicity (NHT); grade 4 neutropenia (NTP) ≥ 7 days and/or neutropenic fever (NTPF); platelets ≤ 25k/mm3 for 7 days or requiring transfusion, or <10k/mm3 for 1 day. Results: The median patient age was 65. Histologies included: 18 FL, 9 MCL, 4 SLL, 3 MZL, 5 transformed lymphoma. Schedule 1: 15 patients were accrued. The only cohort expansion was triggered by a grade 3 diarrhea in cohort 2. No DLT was seen at maximum doses of Bor and C. Schedule 2: Has accrued 24 of 27 planned patients at the time of submission. Due to 2 neutropenic fevers, G-CSF was added, allowing accrual to the highest planned dosing level. Both schedules were well tolerated, with similar toxicity profiles. Most hematologic toxicities (HTs) and NHTs across all dose levels and cycles were grade 1–2. Significant grade 3–4 NHTs included diarrhea (n=1), dehydration (n=1), and neuropathy (n=2). Of 12 patients assessable for response on schedule 1, 2CR, 5 PR, and 5 SD were seen. Of 15 patients thus far assessable on schedule 2, 3 CR, 8 PR, 3 SD and 1 POD were seen. Conclusions: R-CBorP is well-tolerated in patients with NHL when Bor is dosed on a weekly schedule up to 1.8 mg/m2 and twice-weekly up to 1.5 mg/m2. A randomized phase II study is planned to compare these two dosing schedules at their respective MTDs. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech, Millennium Millennium
Oncologic patients in the emergency room
Authors: I. Pajares, M. Tobeña, A. Ferrer, S. Serrano, M. Vidal, D. Lopez, J. Lambea, M. Ruiz-Echarri, E. Millastre, A. Tres
Journal: Journal of Clinical Oncology (2009)

e20748 Background: Cancer is a very frequent pathology with a gradual increase of its prevalence. Oncologic patients are exposed to suffer many complications which may need emergency attention. The aim of this study is to describe patients which consult in the emergency room and frecuency of different causes of complaint. Methods: Between October 2007 and October 2008, we collected all oncologic patients who consulted in our emergency room. We describe tumor location and causes of complaint. Results: 560 oncologic patients were attended in 12 months (median 12 per week). By tumor location, 134 (23,9%) patients had not small cell lung cancer (NSCLC), 101 (18%) colorrectal cancer, 64 (11.4%) breast cancer, and 261 (53%) other malignancies. Of all patients, 440 (82.7%) had stage IV disease and 318 (56.8%) were receiving chemotherapy treatment The most common causes to complaint were oncologic pain (22.5%), fever (17.5%), dysphnea (12.7%), neurologic symptoms (9.1%), and asthenia (8.6%). Conclusions: Oncologic patients consult frecuently in the emergency room, mainly those with NSCLC and colorrectal cancer. Metastasic disease and chemotherapy treatment are common too. Oncologic pain, fever and dysphnea are the most frequent causes of complaint,with an important impact on their quality of life. No significant financial relationships to disclose.
The association of a 17-gene genomic prostate score with adverse surgical pathology and recurrence following surgery for localized prostate cancer (PCa): A comparison of African American and Caucasian patients.
Authors: Jennifer Cullen, Inger L. Rosner, Timothy C. Brand, Amina Ali, Yongmei Chen, Nan Zhang, Athanasios C. Tsiatis, Dejan Knezevic, Tara Maddala, H. Jeffrey Lawrence, Phillip G. Febbo, Shiv Srivastava, Isabell Sesterhenn, David G. Mcleod
Journal: Journal of Clinical Oncology (2015)

86 Background: Molecular assays can improve risk assessment for newly diagnosed PCa, but it is imperative to characterize assay performance in different racial groups, since tumor biology and clinical outcomes may vary. A racially diverse cohort of men (20% AA) with PCa in the Center for Prostate Disease Research multi-center national database was used to determine the association of GPS with outcomes in men treated with radical prostatectomy (RP) for localized PCa. Methods: Biopsy specimens from 431 men treated with RP for NCCN very low, low or intermediate risk PCa at 2 U.S. military medical centers were tested with a 17-gene RT-PCR assay to validate the association between GPS (scale 0-100) and 1) biochemical recurrence (BCR) following RP, and 2) adverse pathology (AP) at RP. BCR was defined as 2 successive PSA levels &gt; 0.2 ng/mL. AP was defined as high-grade (primary Gleason pattern 4 or any pattern 5) and/or pT3 disease. Cox proportional hazards and logistic regression models were used. Results: GPS was obtained in 402 cases (93%), including 82 AA men. A broad range of GPS results was observed in both AA and CA men; GPS distributions were similar between AA (median GPS = 30.3; inter-quartile range (IQR): 23-38) and CA (median GPS = 30.3; IQR: 23-40); no correlation was observed between GPS and race (r = -0.04, p = 0.45). No differences in expression of individual genes or gene groups in the assay were observed between the two groups. In univariable analysis, PSA, biopsy GS and NCCN risk group were associated with BCR and AP, but race was not. The associations between GPS and clinical outcomes were similarly strong and statistically significant in both AA and CA men - BCR HR/20 GPS units = 3.0 (95% CI: 2.0-4.3) for CA vs. 3.5 (95% CI: 1.0-11.7) for AA; AP OR/20 units = 4.0 (95% CI: 2.6-6.6) for CA vs. 2.9 (95% CI: 1.2-7.6) for AA (p &lt; 0.05 for all). Conclusions: In this cohort of patients treated in a health care system with equal access, clinical outcomes and the tumor biology measured by GPS were similar between AA and CA patients. GPS is a significant predictor of BCR and AP in men treated with RP for localized PCa in both AA and CA men.
Abstract #5612: Sulfatase 2 (SULF2) functions as a novel oncogenic protein in hepatocellular carcinoma (HCC)
Authors: Jinping Lai, Tao Han, Catherine Moser, Ileana Aderca, Ju-Seog Lee, Snorri Thorgeirsson, Lewis Roberts
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Background : We are currently investigating new pathways that regulate cell growth, apoptosis and angiogenesis in HCCs, and have shown that the human sulfatase enzyme SULF1 functions as a tumor suppressor. The tumor suppressor activity of SULF1 is mediated through desulfation of cell surface heparan sulfate proteoglycans, which leads to decreased sensitivity to heparin-binding growth factors and increased sensitivity to pro-apoptotic chemotherapeutic agents. The related sulfatase, SULF2, has 61% amino acid sequence identity with SULF1. Aims and Methods : Using oligonucleotide microarray analysis, realtime quantitative PCR, gene transfection, ELISA assay and western blotting, we are investigating the role of SULF2 in carcinogenesis. Results : SULF2 mRNA is high in 8 out 11 HCC cell lines and upregulated in more than half of HCCs as compared with adjacent benign tissues. HCC patients with upregulated SULF2 expression in the tumor tissue have a worse prognosis than those with decreased SULF2 expression (P<0.01). Forced expression of SULF2 in the SULF2-negative Hep3B cell line significantly increases Hep3B cell proliferation and migration and also induces resistance to chemotherapy-induced apoptosis. Forced expression of SULF2 activates both the AKT and ERK44/42 pathways and downregulates activity of the apoptotic caspases 3 and 7. Conversely, knockdown of SULF2 using an shRNA construct targeting the SULF2 mRNA induces profound cell growth arrest and sensitizes the SULF2-expressing HCC cell lines Huh7 and SNU182 to chemotherapy-induced apoptosis. Conclusions : Our results suggest that SULF2 has oncogenic effects in liver carcinogenesis, opposite to the tumor suppressor effects of SULF1 (Supported by NIH Grants CA82862 and CA100882).

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5612.
Progressive varicella presenting with pain and minimal skin involvement in children with acute lymphoblastic leukemia.
Authors: P Rowland, E R Wald, J R Mirro, E Yunis, V C Albo, M R Wollman, J Blatt
Journal: Journal of Clinical Oncology (1995)

Here we report the experience at the Children's Hospital of Pittsburgh (CHP) with varicella zoster virus (VZV) in children with acute lymphoblastic leukemia (ALL). This record review was prompted by a patient with ALL who died suddenly of varicella hepatitis within 24 hours of presentation with a single skin lesion.We reviewed the medical records of children diagnosed with ALL at the CHP from January 1984 through December 1993, who subsequently developed VZV infection.Of 294 patients aged 0 to 15 years, 41 (14%) were identified as having had 42 episodes of VZV infection. Twenty patients (49%) had received prophylaxis with varicella zoster immunoglobulin (VZIG), and all 39 patients in whom the diagnosis was made premortem were treated with acyclovir. Twenty-nine of the 42 cases (70%) had disease limited to the skin. Thirteen cases (30%) had extracutaneous involvement, and five of these episodes (12% of all cases) ended in death. Risk factors for progressive varicella included age greater than 6 years and intensive immunosuppressive therapy at the time of exposure. Six of eight patients with progressive varicella, including two who died, had received VZIG. The clinical presentation in 10 of 13 patients with progressive disease and in four of five patients who died was dominated by severe abdominal and/or back pain. In seven cases, these symptoms preceded the development of skin lesions by several days, and in six patients were associated with extensive involvement of the spleen by varicella, as demonstrated histopathologically by the presence of Howell-Jolly bodies on peripheral-blood smear or radiographically. No patient with uncomplicated varicella was reported to have had premonitory pain.Recognition of these prodromes and suspicion of varicella even in the absence of skin lesions and even in children with a history of prior disease or VZIG administration should prompt early diagnostic and therapeutic measures.
High expression of the chemokine receptor CCR7 is associated with worse outcome in breast cancer
Authors: M. M. Abu-Khalaf, J. Wheler, M. Zerkowski, R. L. Camp, D. L. Rimm, G. G. Chung
Journal: Journal of Clinical Oncology (2005)

9593 Background: Breast cancers can express chemokine receptors to varying degrees, notably CCR7 and CXCR4, whereas their ligands can be expressed on organs that represent important sites of breast cancer metastasis. These findings have implicated chemokines and their receptors in directing breast cancer cells to specific sites of metastasis. Using a breast cancer tissue microarray (TMA), we analyzed the protein expression and sub-cellular localization of CCR7 and CXCR4. Methods: Our TMA consisted of 659 cases of primary breast cancers, nearly equally divided between node negative and node positive cancers. We used our automated quantitative image analysis software (AQUA), which uses a modified immuno-histochemistry technique with fluorochromes as a detection method. Primary antibodies were monoclonal CCR7 (BD Pharmagin, Minneapolis, MN) and CXCR4 (R&D Systems, Minneapolis, MN). All statistical analyses were performed using Statview software (version 5.0.1; SAS Institute Inc., Cary, NC). The total tumor and sub-cellular distribution pattern of CCR7 and CXCR4 were then correlated with clinico-pathologic factors and outcome. Results: CCR7 stained predominantly in a membrane/cytoplasmic distribution, whereas CXCR4 stained more diffusely throughout the entire tumor. We chose to divide the AQUA continuous data into traditional quartiles. This showed that the highest 25% of CCR7 expressers had a worse disease-specific survival when compared to the lowest 25% expressers (p=0.03). No significant correlation was identified between CCR7 expression and ER/PR, HER2/neu, nodal status, tumor size or nuclear grade. CXRC4 expression within the entire tumor or within the subcellular compartments was not associated with any of the clinico-pathologic variables or clinical outcomes. Conclusions: CCR7 and CXCR4 are variably expressed in breast cancers. Highest expression of the chemokine receptor CCR7 correlates with poor survival, without significant correlation with other clinico-pathologic factors. No significant financial relationships to disclose.