tbuckley/cabot-search huggingface dataset:
Immunochemotherapy with temozolomide and rituximab for central nervous system lymphomas in an elderly population
Authors: P. Spadaro, V. Pitini, C. Arrigo, C. Amata, I. La Torre, G. Toscano
Journal: Journal of Clinical Oncology (2005)

6633 Background: Primary central nervous system lymphoma (PCNSL) is an aggressive non-Hodgkin’s lymphoma arising within the brain in the absence of a systemic disease. High-dose methotrexate (MTX) followed by whole-brain irradiation therapy has consistently improved the length of survival in PCNSL, however, it is noteworthy that patients with an age >60 years and with renal dysfunction are precluded to high-dose systemic MTX.Previous studies have confirmed the activity of temozolomide and rituximab in the treatment of PCNSL. This association would be favourable for patients with impaired renal function. We report our experience with an immunochemotherapy regimen consisting of rituximab and temozolomide in patients with PCNSL. Methods: Between May 2003 and February 2004, 10 consecutive non- immunocompromised patients with PCNSL histologically documented CD20+ (6 males and 4 females) older than 60 years and with poor renal function were enrolled in this study, median Karnofsky status was 70%. Patients were scheduled to receive rituximab (375 mg/m2) on day 1 and temozolomide at a dose of 200 mg/m2 on days 1–5, repeated after 28 days for 8 cycles. A gadolinum-enhanced magnetic resonance image of the head was obtained after every two cycles of treatment. Results: After four cycles of rituximab and temozolomide, confirmed objective responses were observed in 6 patients (4 CR + 2 PR) resulting in a response rate of 60%, 4 patients had progression disease. Among the six responder patients after completion of planned therapy, the four patients, with a CR after 4 cycles, maintained a CR. One patient with PR achieved a CR. The median response duration was 7 months and the median survival time was 10 months. Three patients experienced grade 3 neutropenia and two patients experienced grade 3 thrombocytopenia. Conclusions: Initial results indicate that immunochemotherapy with rituximab and temozolomide is well tolerated and exhibited efficacy in these elderly patients. Treatment with rituximab followed by an alkylator such as temozolomide may offer synergic killing lymphoma cell without overlapping toxicities. No significant financial relationships to disclose.
Correlation of RRM1 expression in muscle invasive locally advanced urothelial cancer with age
Authors: L. C. Harshman, G. Bepler, Z. Zheng, J. P. Higgins, G. I. Allen, R. Tibshirani, S. Srinivas
Journal: Journal of Clinical Oncology (2009)

e16021 Background: RRM1, the regulatory subunit of ribonucleotide reductase, plays a role in DNA repair after chemotherapy damage and in gemcitabine metabolism. Prior studies demonstrated a survival benefit to high expression in resected early stage lung cancer and a trend toward longer time to progression with low expression in advanced bladder cancers treated with gemcitabine and cisplatin. We hypothesized that patients with resected locally advanced (T2–4NxM0) urothelial transitional cell carcinoma (TCC) whose tumors had higher RRM1 expression would have longer overall survival (OS). Methods: 84 radical cystectomy specimens with muscle invasive TCC were identified from existing tissue microarrays (TMAs) containing 343 specimens. The medical records of these patients were retrospectively reviewed to confirm pathology and stage. Presence of muscle invasion was required. Specimens were analyzed for RRM1 expression using AQUA. The median value of RRM1 was established a priori as the cutoff for high and low expression. Results: Median age of the patients was 69.3 years. There was near equal distribution of stages: 30%, 38%, and 32% for stage II, III, and IV respectively. The majority were high grade (99%) with no nodal involvement (69%). Median OS was 2.0 years (0–13.1). Median RRM1 expression was 1493.3. Degree of RRM1 expression did not correlate with OS, but when adjusted for age, adding an interaction term, high RRM1 expression in younger patients correlated with increased OS (p = 0.0278). Median OS for high expressors age &lt;69.3 years was 6 years compared to 2.3 years for low expressors. 35% of patients less than 70 years were high expressors. Conclusions: Our results suggest that high RRM1 expression may be a prognostic factor for improved survival in locally advanced TCC patients less than 70 years old. These results deserve further study in a larger prospective analysis with disease-specific survival assessment and correlation with other possible prognostic genes such as ERCC1. [Table: see text]
The rGel/BLyS fusion toxin inhibits malignant B cells and blocks endogenous NF-κB signaling pathways
Authors: Mi-Ae Lyu, Kwang Seok Ahn, Bharat Aggarwal, Lawrence Cheung, Michael Rosenblum
Journal: Cancer Research (2007)

4876   Mantle cell lymphoma (MCL) and diffuse large B cell lymphoma (DLBCL) are aggressive sub-types of B-cell, non-Hodgkin’s lymphomas. Growth signaling pathways mediated in part through the NF-κB signaling pathway and the growth factor B lymphocyte stimulator (BLyS) are commonly constitutively expressed in malignant B cell lines. Activation of NF-κB signaling and BLyS expression both play important roles in B-cell development and survival. We previously generated a fusion toxin designated rGel/BLyS for receptor-mediated delivery of the rGel toxin to the malignant B cells. Three MCL cell lines (JeKo-1, Mino, and SP53) and two DLBCL cell lines (SUDHL-6 and OCI-Ly3) expressing all three distinct BLyS receptors (BAFF-R, TACI, and BCMA) were found to be the most sensitive to the cytotoxic effects of the fusion toxin compared to rGel itself. The rGel/BLyS fusion toxin inhibited NF-κB DNA-binding activity after 7 hr of treatment (80% and 60% inhibition for Mino and OCI-Ly3, respectively) and suppressed constitutive NF-κB activity in a dose and time-dependent manner in both MCL and DLBCL lines. The rGel/BLyS fusion toxin blocked Akt phosphorylation after 1 hr of treatment and induced down-regulation of phospho Akt in a time-dependent manner. We also found that rGel/BLyS down-regulated levels of Mcl-1, Bcl-x L  and cyclin D1, but not Bcl-2 and Bax. In addition, treatment of cells with rGel/BLyS induced apoptosis through caspase-3 activation and PARP cleavage. Our results suggest that constitutive NF-κB expression plays an important role in regulating B-cell growth and that the cytotoxic effects of this fusion toxin appear to be mediated, at least in part, by inhibiting these critical growth stimulatory pathways. This also suggests that rGel/BLyS may be an excellent candidate for the treatment of B-cell malignancies including MCL and DLBCL. Research conducted, in part, by the Clayton Foundation for Research.
Criticisms of the psychopathological interpretation of witch hunts: a review
Authors: T J Schoeneman
Journal: American Journal of Psychiatry (1982)

The psychopathological interpretation of the European witch hunts of the 16th and 17th centuries, which has been prominent in histories of psychiatry, contends that demonology overwhelmed psychiatry in the late middle Ages, with the result that the mentally ill were executed by the thousands as witches. The author reviews the criticisms and contrary evidence that have been brought to bear on this paradigm in the past 20 years, including critiques of its data collection and interpretation, historical evidence which has failed to support its contentions, and questions about its implicit approach to the history and philosophy of science.
Hepatic intra-arterial chemotherapy with gemcitabine: An ongoing phase II study in patients with liver metastases of breast cancer
Authors: K. Eichler, S. Zangos, M. G. Mack, J. O. Balzer, O. Söllner, C. Herzog, K. Engelmann, T. J. Vogl
Journal: Journal of Clinical Oncology (2004)

738 Background: Purpose: To evaluate the efficacy and tolerability of hepatic intra-arterial chemoembolization with gemcitabine as a cytostatic agent in pts with inoperable liver metastases of breast cancer. Methods: Ongoing, open-label, single-center study design; pts had histologically confirmed breast cancer with inoperable liver metastases, adequate bone marrow reserve, sufficient liver/renal function, no active CNS metastases, KPS >70%, and life expectancy > 12 weeks. A suspension of gemcitabine 1,200 mg/m2, 10 ml/m2 of iodised oil (Lipiodol), and 5 ml of a degradable starch microsphere (Spherex) suspension, is administered intra-arterially up to 3 times every 4 wks. Dose-limiting toxicity (DLT) is defined as grade 4 thrombocytopenia, neutropenia, or nonhematologic toxicity > grade 3. Tumor response is evaluated by magnetic resonance (MRT) and computed tomography (CT) imaging. Results: 15 pts enrolled (median 58 yrs, range 48–65). All pts tolerated the treatment well, with no DLTs. Five pts (33%) achieved a partial response, 8 stable disease, and 2 progressed. Conclusions: These first results indicate that hepatic intra-arterial chemotherapy with gemcitabine is well tolerated and achieved encouraging response rates in pts with liver metastases of breast cancer. (This study is supported in part by Eli Lilly Oncology.) No significant financial relationships to disclose.
Abstract 3555: Akt kinase-interacting protein1 as a potential therapeutics target in CREB1 signaling in malignant pleural mesothelioma
Authors: Tadaaki Yamada, Joseph M. Amann, Konstantin Shilo, Naoya Fujita, Seiji Yano, David P. Carbone
Journal: Cancer Research (2015)

Abstract Background: Diffuse malignant mesothelioma (DMM) is an aggressive tumor arising from the mesothelial cells of serosal membranes. As conventional treatment regimens are commonly unsuccessful in changing its outcome, novel effective therapeutic strategies based on the molecular mechanisms of disease are needed to improve the prognosis of DMM. Akt kinase-interacting protein1 (Aki1), known as a scaffold protein of PI3K/PDK1/Akt that determines receptor signal selectivity for EGFR, has been suggested as a therapeutic target in lung cancer. The aim of this study was to evaluate Aki1 as a potential therapeutic target for treatment of DMM. Methods: DMM cell lines (211H, H290, H2052, H2373, H2452, Y-meso8A, and Y-meso14) and immortalized human mesothelial cells (Met-5A) were employed for evaluation of effects of treatment with Aki1 or CREB1 siRNAs on cell viability by MTT assay, cell cycle by FACS analysis, cell signaling by WB, and CREB transcriptional activity. The efficacy of Aki1 siRNA against growth of 211H cells was investigated in an orthotropic implantation model using SCID mice. We further examined Aki1 and p-CREB1 expression in DMM tumors from 35 patients utilizing tissue microarray and resection specimens. Results: Cell based assay showed that silencing of Aki1 inhibited cell viability and caused cell arrest of mesothelioma cell lines but not immortalized mesothelial cells (Met-5A). Importantly, we identified that the efficacy of Aki1 is regulated by CREB1 signaling which is involved in cell viability, cell cycle, and transcriptional activity. Application of Aki1 siRNA significantly inhibited growth of 211H cell line within pleural cavity compared with that of control siRNA in an orthotropic implantation model (p = 0.006). Aki1 and phosphorylated CREB1 were frequently expressed in DMM patients (65/68 and 30/35 cases, respectively). Furthermore, the expression of Aki1 correlated with phosphorylation of CREB1 (Spearman rank correlations = 0.521; p = 0.002). Conclusions: Our data suggest that Aki1/CREB axis may regulate the survival signaling, and may therefore be a potent target for DMM patients. Citation Format: Tadaaki Yamada, Joseph M. Amann, Konstantin Shilo, Naoya Fujita, Seiji Yano, David P. Carbone. Akt kinase-interacting protein1 as a potential therapeutics target in CREB1 signaling in malignant pleural mesothelioma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3555. doi:10.1158/1538-7445.AM2015-3555
Extended-field radiotherapy is superior to MOPP chemotherapy for the treatment of pathologic stage I-IIA Hodgkin's disease: eight-year update of an Italian prospective randomized study.
Authors: G P Biti, G Cimino, C Cartoni, S M Magrini, A P Anselmo, R M Enrici, G P Bellesi, A Bosi, G Papa, D Giannarelli
Journal: Journal of Clinical Oncology (1992)

PURPOSE To compare the effectiveness of chemotherapy (CHT) with extended-field radiotherapy (RT) in the treatment of early-stage Hodgkin's disease (ESHD), we report an 8-year updated analysis of a study in which treatment with six cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) CHT was randomly compared with extended-field RT. PATIENTS AND METHODS From August 1979 to December 1982, 89 adult patients with pathologic stage I-IIA Hodgkin's disease (HD) were randomly allocated to receive either RT with mantle field followed by periaortic irradiation (n = 45) or six monthly courses of MOPP CHT (n = 44). RESULTS All patients in the RT arm and 40 of 44 in the CHT arm achieved complete remission. Twelve relapses occurred in each group. Eight patients treated with MOPP and two of the RT arm died of HD. Three other patients of the CHT group died because of a second cancer. With a median follow-up greater than 8 years, the overall survival rate is significantly higher in the RT than in the CHT group (93% v 56%; P less than .001), whereas the rates of freedom from progression and relapse-free survival (RFS) were similar in the two groups (76% v 64% and 70% v 71%, respectively). Of the 12 patients relapsing after RT, 11 (92%) achieved a second CR, compared with only six of the 12 (50%) in the MOPP group. Analysis of the response rate to salvage treatments showed that the type of relapse in the MOPP group was a prognostic indicator for the achievement of a second CR, whereas in the RT group, a second CR was obtained regardless of the characteristics of the relapses. At 80 months, the probability of survival of relapsing patients calculated from time of relapse was 85% and 15% in the RT and CHT groups, respectively (P = .02). CONCLUSION We conclude that RT alone is the treatment of choice for adult patients with ESHD with favorable prognostic factors.
Government “attack on local democracy” could undermine ethical and pro-health investing
Authors: Adrian O’Dowd
Journal: BMJ (2016)

Proposals to change the rules on where local authorities can invest their pension funds could restrict decisions about disinvestment in what some councils see as unethical projects, particularly in the tobacco and oil industries.

MPs, campaigners, and charities have all raised concerns over planned amendments to the Local Government Pension Scheme Regulations 2009, which are currently out for consultation until next month.1

The Department for Communities and Local Government is consulting on changes to pension regulations, alongside new procurement guidelines to stop local authorities operating “municipal foreign and defence policies” through “politically motivated boycott and divestment campaigns.”

Although the changes seem to be focused on foreign policies, they could also affect any decisions by councils to stop investing in the tobacco industry or oil industry.

A spokesman for the Department for Communities and Local Government told The BMJ , “Councils should not be using pensions and procurement policies to pursue their own boycotts and sanctions against foreign nations. We are tightening up the rules …
Detection of the AT1 and AT2 receptors of <i>angiotensin II</i> in malignant breast tumors and its correlation to cellular proliferation, hormonal profile and prognosis
Authors: O. Arrieta, T. Ceron-Lizarraga, D. Morales-Espinoza, G. Vizcaino, A. Gamboa, B. Pineda
Journal: Journal of Clinical Oncology (2006)

10632 Background: Angiotensin II (ANG II) is the main effector peptide of the Renin-Angiotensin-Aldosterone System. ANG II has multiple physiologic effects and recent studies have demonstrated that is an angiogenic factor in non-tumoral experimental models. We demonstrated that malignant glioma cells express both receptors and the blockage of AT1 inhibits tumoral growth in vivo, and induces apoptosis. Studies on the ANG II receptors’ subtypes in adenocarcinoma of the breast in mice have demonstrated high expression of AT1; nevertheless, their expression in breast cancer hasn’t been studied. The objective of this study was to determine the presence of the ANG II receptors AT1 and AT2 in human breast cancer and their association to vascularity, cellular proliferation, hormone receptors; as well as to the disease free survival. Methods: Malignant breast tumors (n = 78) from patients who underwent surgery were collected between 2000 and 2004. Patients with neoadjuvant chemotherapy or radiotherapy were excluded. The AT1 and AT2 receptor expression was performed by RT-PCR and immunohistochemistry. The control samples were 8 breast fibromas. Results: The median age of patients was 54.7 years, the pathological stage included stage I (15.5%), II (65.5%) and III (18.9%). The patients underwent radical mastectomy in 61.4 % and conservative surgery in 39%. The median survival was 82 ± 5 months. AT1 and AT2 expression was found in 66% and 55%, respectively The coexpression of AT1 and AT2 receptors was positive-positive in 55% o and negative-negative in 16% of the tumors (p = 0.045). None of the benign tumors showed AT1 and AT2 expression (p = 0.01). The associated factors survival were stage (p = 0.03, log rank = 0.05) and differentiation grade. The AT1 receptor expression was associated with presence of estrogen receptors (p = 0.05), mitosis index (p = 0.05), cellular proliferation index (p = 0.01) and vascular density (p = 0.05). Conclusions: There is an important expression of the ANG II receptors AT1 and AT2 in breast cancer. AT1 and AT2 participate in cellular proliferation mechanisms of breast cancer and may play an important role in its biology, thus making them potential therapeutic targets. No significant financial relationships to disclose.
Lack of apparent difference in outcome between clinically staged IIIA and IIIB non-small-cell lung cancer treated with radiation therapy.
Authors: W J Curran, P M Stafford
Journal: Journal of Clinical Oncology (1990)

The current American Joint Committee on Cancer (AJCC) staging system for bronchogenic carcinoma, which divides stage III M0 cases into stages IIIA and IIIB, is based on the observation that selected patients with IIIA disease (T3 or N2) can undergo complete surgical resection, in distinction to IIIB patients (T4 or N3). To understand the value of this system when applied to clinically staged (CS) patients treated with a standard nonoperative approach, the records of patients with squamous cell, large-cell, and adenocarcinoma of the lung treated with radiation therapy (RT) at the Fox Chase Cancer Center from 1978 to 1987 were reviewed. Three hundred sixteen patients were identified as having CS III M0 disease treated with single daily fraction RT without chemotherapy or sensitizers. Of these, the distinction between IIIA (166) and IIIB (140) could be made for 306 patients. The median survival time (MST) for all CS III patients was 9.6 months, and the 2-year survival was 17%. No difference was observed in MST between CS IIIA and IIIB patients (9.4 v 9.8 months, P = .78), in 2-year survival (17% v 18%), or in rate of first failure within the RT field (43% v 44%). MSTs for the 157 CS IIIA and IIIB patients with less than 5% weight loss and Zubrod performance status (PS) 0 to 1 were 13.0 and 15.8 months (P = .29), respectively. This lack of difference in outcome for CS IIIA and IIIB patients receiving RT has important implications in the design and stratification of future nonoperative trials for stage III lung cancer.
Gemcitabine, cisplatin and methylprednisolone (GEM-P) in patients with T-cell lymphoma: Results from The Royal Marsden Hospital
Authors: H. Arkenau, M. Trumper, B. Sirohi, G. Chong, I. Chau, A. Wotherspoon, A. Norman, A. Horwich, E. Matutes, D. C. Cunningham
Journal: Journal of Clinical Oncology (2006)

17507 Background: There is a need for novel, effective therapies for T-cell non-Hodgkin’s lymphoma (NHL). The combination of gemcitabine, cisplatin and methylprednisolone (GEM-P) has shown activity in patients (pts) with relapsed Hodgkin’s disease and NHL (Chau I et al. Br J Haematol 2003, Baetz T et al. Ann Oncol 2003). We report a single institution retrospective analysis of GEM-P for pts with T-cell NHL. Methods: Sixteen pts with T-cell NHL treated at the Royal Marsden Hospital between June 2001 and March 2005 with GEM-P (gemcitabine 1 g/m 2 D1, 8, 15; cisplatin 100 mg/m 2 D15; methylprednisolone 1 g D1–5, repeated every 28D) were identified. Results: 16 pts (9 males and 7 females) were analysed. Histological subtypes were: angioimmunoblastic (n = 5), T-cell enteropathy (n = 2), NK/T cell nasal-type (n = 2), T-cell anaplastic (n = 3) and peripheral T-cell unspecified (n = 3). Median age was 55 years (range: 18–71 years), 69% had IPI-score ≥ 2 and 69% had stage III/IV disease. 15 /16 pts were pre-treated: median number of prior treatments: 1 (range: 0–4). At the start of GEM-P treatment pts presented with: primary refractory disease (n = 3), 1 st relapse (n = 6), 1 st relapse refractory (n = 3), 2 nd relapse (n = 2) and 4 th relapse (n = 1). Median time from diagnosis of T-cell NHL to start of GEM-P was 8.9 months(m) and median number of cycles given was 3 (range: 1–6). Of 16 evaluable patients, 3 pts (19 %) achieved complete remission (CR), 8 pts (50 %) achieved partial remission (PR), (ORR= 69%; CI-95% 41.4–89.0) and 5 pts (31%) progressed while on GEM-P. One pt received high dose chemotherapy (melphalan/etoposide) after CR to GEM-P. After a median follow up of 17.4m the mean progression free survival (PFS) was 9m (range 1.15–37.5). The median overall survival (OS) has not been reached and the survival probability at 1 year was 68.2% (95% CI: 40–85). The main grade 3/4 toxicities were myelosuppression (leucopenia 62%, neutropenia 62% and anaemia 12%) and required granulocyte colony stimulating factor (GCSF) in 3 pts with neutropenic sepsis and in 1 pt with neutropenia. Conclusion: GEM-P has encouraging efficacy with an acceptable toxicity profile in pts with previously treated T-cell NHL. [Table: see text]
Bowel Preparation, Colonoscopy Withdrawal Time and Adenoma Detection Rate: A Prospective Study of Screening Colonoscopies
Authors: Martin C.S. Wong, Simon S.M. Ng, Jessica Y.L. Ching, Victor C.W. Chan, Jeffrey P. Shum, Siew C. Ng, Sunny H. Wong, Thomas Y.T. Lam, Arthur K.C. Luk, Justin C.Y. Wu, Francis K.L. Chan, Joseph J.Y. Sung
Journal: Clinical Gastroenterology and Hepatology (2015)