tbuckley/cabot-search huggingface dataset:
Overpopulation and overconsumption. Combating the two main drivers of global destruction [editorial]
Authors: Smith R
Journal: BMJ (1993)

Commentary is directed to the accomplishments of the Earth Summit in Rio de Janeiro and responses to overpopulation.  The benefit of the summit was not in the agreements but in the debate.  The overwhelming understanding was that environmental degradation is linked with overpopulation poverty development excessive consumption and relations between rich and poor nations.  Inadequate attention in the final statement was directed to overpopulation and overconsumption.  The US President in a reelection position remained noncommittal on overconsumption.  The Vatican and anti-abortion lobbies influenced the position on overpopulation.  Population control will be a sensitive issues in the 1990s because rich countries are in an awkward portion to preach about overpopulation to poor countries where most population growth is occurring.  There are many complex factors involved with the issue of population growth.  State intervention in personal decision making has not always as in the case of India and China been without excess.  Politicians are afraid of losing the Catholic vote.  Mistakes have been made in the dire predictions of the 1960s.  None of these reasons is sufficient to ignore or become bored with overpopulation. Population growth has resulted from lower global death rates and birth rates which have fallen only in the rich world.  It is likely that world population will grown by 3.5 billion or more to reach 8 billion in 2025.  This means a fourfold decrease over 100 years.  Population must be kept on government agendas at the village state and international level.  One way to accomplish this end is for physicians to become more politically involved within their profession and in conjunction with other professions.  Collaboration between professions will contribute to better solutions and to a larger pressure group at the world conference on overpopulation in Cairo in order to overwhelm the small interests that dominated past world conferences.  Notwithstanding population increases energy consumption increases grew even faster.  Energy consumption grew from 1 terawatt in 1890 to 3.3 terawatts in 1950 and to 13.7 terawatts in 1990.  So far growth is concentrated in developed countries and is linked with standard of living.  Energy availability will not keep pace with demand.
Delivery of oncolytic adenovirus into the nucleus of tumorigenic cells by tumor microparticles for virotherapy
Authors: Li Ran, Xiaohua Tan, Yanchun Li, Huafeng Zhang, Ruihua Ma, Tiantian Ji, Wenqian Dong, Tong Tong, Yuying Liu, Degao Chen, Xiaonan Yin, Xiaoyu Liang, Ke Tang, Jingwei Ma, Yi Zhang, Xuetao Cao, Zhuowei Hu, Xiaofeng Qin, Bo Huang
Journal: Biomaterials (2016)
Phase I trial of lomeguatrib (PN) combined with dacarbazine (DTIC) for treatment of patients with melanoma and other solid tumors: Initial results
Authors: H. Tawbi, A. Tarhini, S. Moschos, M. Sulecki, F. Viverette, R. Radkowski, J. Shipe-Spotloe, C. Kunkel, M. Rae, J. Kirkwood
Journal: Journal of Clinical Oncology (2006)

8016 Background: TheDNA repair enzyme O 6 -Alkylguanine Alkyltransferase (AGT) directly reverses the O 6 -methylguanine (O 6 -MeG) base lesion induced by treatment with DTIC. Depletion of AGT using O 6 -MeG analogs enhances the cytotoxicity of DTIC in preclinical models and in early phase trials of O 6 -Benzylguanine. Lomeguatrib (Patrin, PN) is an orally bioavailable highly potent O 6 -MeG analog that is well tolerated as a single agent. We report the first phase I experience of PN combined with DTIC in patients who have failed prior systemic therapy. Methods: This open-label phase I study was performed to determine the toxicity profile and maximum tolerated dose (MTD) of PN given orally for 5 or 10 days (d) combined with a single dose of DTIC administered IV on d 2, repeated on a 21 d schedule. Of 30 pts enrolled 25 (83%) had metastatic melanoma, and all had ECOG PS ≤2. Dose escalation started at 40 mg of PN once daily for 5 d and 500 mg/m 2 of DTIC. 6 pts failed prior chemotherapy, 16 failed prior immunotherapy, and 3 failed both. 5 pts had no prior systemic therapy. Results: Adverse events observed in more than 50% of pts included gr 1–2 nausea and vomiting and gr 1–2 fatigue. Hematologic toxicity was prominent with gr 3–4 neutropenia (13/30, 43%) and gr 3–4 thrombocytopenia (4/30, 13%) even at doses of DTIC 50% of usual clinical doses. Prolonged neutropenia accounted for all dose-limiting toxicities (DLT) observed so far. The MTD has not been reached, however hematologic toxicities requiring dose modifications of DTIC have been frequent (42% of all cycles administered). 16 pts (53%) had stable disease as their best response with a median time to progression of 53 days (95% C.I. 40–86 days). Conclusions: Oral administration of PN substantially alters the toxicity and tolerance of DTIC inducing prolonged hematologic toxicity at doses &lt;50% of doses in routine usage. The study is ongoing to determine the MTD of PN combined with DTIC after which a phase II trial will be completed in pts who have not had prior chemotherapy. Pending completion of accrual (total of 40 pts by May 2006) the recommended phase II dosage appears to be PN 40 mg orally BID for 10 days combined with 400 mg/m 2 of DTIC. [Table: see text]
Abstract 15119: T2-weighted Magnetic Resonance Imaging Accurately shows Treatment Response of Novel Neuroprotective Compound, Tat-N-dimer, in Ischemic Stroke
Authors: Andreas E Clemmensen, Lotte K Kristensen, Carsten H Nielsen, Flemming F Johansen, Andreas Kjær
Journal: Circulation (2014)

Introduction:  Tat-N-dimer is a promising drug in stroke therapy targeting the interaction between postsynaptic density protein 95 (PSD-95) and neuronal nitric oxide synthase (nNOS) downstream of the N-methyl-D-aspartate receptor (NMDAR). Studies have shown a neuroprotective effect of the drug with 40% reduction in infarct volume following permanent middle cerebral artery occlusion (pMCAO) in mice. Using high-field, T2-weighted magnetic resonance imaging, the volume of the edema and the total lesion can be estimated precisely.   Hypothesis:  Mice undergoing pMCAO have significantly reduced infarct and edema volumes following treatment with Tat-N-dimer, compared to matched controls.   Methods:  Thirty-six male C57Bl/6J mice were subjected to pMCAO and randomly assigned to receive either physiological saline (n=16) or 3 nmol/g Tat-N-dimer (n=16) and allowed 28 days of survival. At 6 hours, 48 hours, 7 days and 28 days post-occlusion, mice were subjected to MR imaging on a Bruker BioSpec 700/20 7T pre-clinical scanner. A T2-weighted 3D TurboRARE with TE and TR of 32 ms and 1500 ms, respectively, was used. Ten mice were randomly selected for histological assessment of infarct volumes.   Results:  Total lesion volumes were significantly different over the time course of the experiment (p   Conclusions:  Tat-N-dimer has a neuroprotective effect on mice exposed to pMCAO, which can be accurately evaluated by T2-weighted MR imaging.
Docetaxel versus epirubicin/cyclophosphamide (EC) as first-line therapy in metastatic breast cancer (MBC): Results from the randomized phase II TIPP study
Authors: C. Wasemann, A. Ertan, C. Strunck, W. Schmidt, K. Diedrich, M. Friedrich
Journal: Journal of Clinical Oncology (2004)

823 Background: Docetaxel is one of the most active single-agent therapies for MBC and may produce higher response rates than current standard regimens. This two-centre randomized, phase II study of docetaxel vs EC was initiated to investigate the therapeutic potential of single-agent docetaxel as first-line therapy for MBC. Methods: Patients (pts) with MBC (no prior chemotherapy for metastatic disease) and WHO performance status 0–1 are eligible for the study. Accrual of 60 patients is planned. Pts are randomized to either docetaxel 100mg/m2 as a 1-hour intravenous infusion (with standard oral dexamethasone premedication) or epirubicin 90mg/m2 followed by cyclophosphamide 600mg/m2, each administered as an intravenous bolus. Both regimens are repeated every 3 weeks for a maximum of 6 cycles. Results: To date, interim data are available for 34 patients (docetaxel 14, EC 20) who have completed 6 cycles of therapy. In total, 24, 31, and 34 pts are evaluable for tumor response, efficacy, and toxicity, respectively. Two pts died after the first cycle of treatment and 1 pt had only received 1 cycle of treatment at the time of evaluation. Overall response rates were 70% and 64% for docetaxel and EC, respectively (p=ns). Median time to response was significantly shorter for docetaxel compared with EC (3.0 vs 5.7 weeks, p=0.044) and median time to progression was similar for both groups (35.9 vs 39.9 weeks, respectively). To facilitate the comparison of toxicity between treatments, we calculated the mean incidence per cycle of WHO grade toxicities. Grade 1–3 neurotoxicity was reported by significantly more pts receiving docetaxel compared with EC (p=0.028). There were no reports of clinical grade 4 toxicity for either regimen. Conclusions: These preliminary phase II data suggest that docetaxel is as effective and well tolerated as EC when used as first-line treatment for MBC. More mature data for 42 pts, including hematotoxity results, will be available by ASCO. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis
A phase I study of anti-CD123 monoclonal antibody (mAb) CSL360 targeting leukemia stem cells (LSC) in AML.
Authors: A. W. Roberts, S. He, D. Ritchie, M. S. Hertzberg, I. Kerridge, S. T. Durrant, G. Kennedy, I. D. Lewis, P. Marlton, A. J. McLachlan
Journal: Journal of Clinical Oncology (2010)

e13012 Background: Eradication of LSC is a goal of anti-leukemic therapy. AML LSC found in CD34+CD38- cell fractions express high levels of IL-3Rα (CD123), unlike CD34+CD38- cells from normal samples. CSL360 is a recombinant, chimeric IgG1, anti-CD123 mAb that neutralizes IL-3 and has anti-leukemic activity preclinically in vitro and in vivo. Methods: A phase I, escalating-dose study of CSL360 assessed safety, PK, immunogenicity, and bioactivity. Relapsed, refractory, or high-risk AML patients (pt) received 12 weekly, iv infusions, unless withdrawn early due to treatment-related toxicity or progressive disease (PD). Pts who achieved clinical response could receive additional doses. Blast counts in blood and marrow, % LSC in marrow, CD123 levels, extent of receptor binding, and ex vivo signaling of blast cells were measured. Results: In total 304 iv infusions were administered to 40 pts across 5 dose levels (0.1-10 mg/kg). Reasons for discontinuation were: PD (20), completed 12 doses (11), SAE (3), withdrew consent or investigator decision (6). Complete, sustained saturation and down-regulation of CD123 occurred at ≥ 3 mg/kg and abolished ex vivo proliferative responsiveness of blasts to IL-3, indicating abolition of IL-3 signaling. Treatments were safe; MTD was not reached. AEs and SAEs did not increase with increasing dose level; 5/62 (8%) SAEs were related/possibly related to treatment. AUC and Cmax increased proportionally (linear kinetics); T ½ was 4.1 days. Immunogenicity was detected in lower dose level cohorts only. Changes from baseline in % LSC in marrow were inconsistent and minor except for a large increase in one pt. One other pt (relapsed after 2 allo-SCT, including 1 double cord SCT) became leukemia-free after 3 doses, achieved CR after 12 doses, withdrew after 17 doses (SAE) and remained in CR at last follow up. No other pt had objective response or definitive clinical benefit. Conclusions: CSL360 bound CD123 specifically and safely but without clear anti-leukemic activity in high risk AML pts, suggesting blockade of IL-3 signaling is an insufficient therapeutic strategy. Improving ADCC by enhancing Fc- mediated effector function of an anti-CD123 mAb could be efficacious against AML LSC and blasts. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration CSL Ltd.
Low doses of PEG-coated gold nanoparticles sensitize solid tumors to cold plasma by blocking the PI3K/AKT-driven signaling axis to suppress cellular transformation by inhibiting growth and EMT
Authors: Nagendra Kumar Kaushik, Neha Kaushik, Ki Chun Yoo, Nizam Uddin, Ju Sung Kim, Su Jae Lee, Eun Ha Choi
Journal: Biomaterials (2016)
Role of Hospital Anxiety &amp; Depression scale in reducing need of a formal psychiatric referral in cancer patients
Authors: A. Vora, P. M. Parikh, N. Shanthi, V. R. Pai, N. Prasad, S. Goswami, S. Shah
Journal: Journal of Clinical Oncology (2005)

8037 Background: Majority of the newly diagnosed cancer patients suffer from depression or anxiety. Involving a psychiatrist for all cancer patients at diagnosis is not practical-particularly for developing countries. There are several tools available in the market to objectively assess depression & anxiety. We therefore studied whether simple and easy to administer HAD scale could help select subset of patients that really need further evaluation by a psychiatrist. Methods: HAD (Hospital Anxiety and Depression) scale was used to assess depression or anxiety in our outpatient cancer patients. Evaluation of these patients was done only once (no follow-up planned). The questionnaire was self administered and data was compiled by a nurse who had no qualification or training in psychology. The average time to fill one questionnaire was 5 minutes. The HAD results were co-related with the data obtained by a qualified psychologist who utilized the Hamilton scale. Results: A total of 300 patients filled the questionnaire. HAD Score indicated: No depression in 46%, borderline 24%, severe depression in 30%. For anxiety, normal 47%, doubtful 28% and severe anxiety in 25%. The subset of 30 random patients who were also independently evaluated by a clinical psychologist showed interesting finding:(Table 1). Normal and high/definitive score on both scales co-related well. Conclusion: HADS is a good and simple instrument for rapid evaluation of psychological problems in physically ill cancer patients. There is a good co-relation between HADS and Hamilton scale for absent/definite anxiety and or depression. Only patients with doubtful/borderline anxiety or depression on HADS need further evaluation by a qualified psychologist/psychiatrist. Thus HADS can be a cost-effective way of screening all cancer patients for anxiety and/or depression. No significant financial relationships to disclose.
Contribution of FOXC1 to the progression and metastasis and prognosis of human colon cancer.
Authors: Dawei Li, Qingguo Li, Changhua Zhuo, Ye Xu, Sanjun Cai
Journal: Journal of Clinical Oncology (2015)

636 Background: Distant metastasis remains the most common causes to death of colon cancer. Thus it is crucial to identify the molecular markers associated with the progression and metastasis of this disease. Recent evidence for overexpression of FOXC1 in several types of human cancer suggests that it might play a key role in tumor biology. However, the clinical significance of FOXC1 signaling in human colon cancer pathogenesis remains unknown. Methods: We investigated FOXC1 expression in 203 cases of primary colon cancer and matched normal colon tissue and lymph node matastasis in a tissue array. The underlying mechanisms of altered FOXC1 expression and the impact of this altered expression on colon cancer growth and metastasis was explored both in vitro and in vivo. Results: We found elevated expression of FOXC1 protein in cancereous tissue and lymph node metastases than adjacent normal colonic tissues. Overexpression of FOXC1 was associated with higher clinical stage, T stage, lymph node metastasis and presence of distant metastasis. FOXC1 served as an independent prognostic marker whose expression levels correlated with poorer metastasis-free survival (MFS) and poorer overall survival (OS). A Cox proportional hazards model revealed that FOXC1 expression was an independent prognostic factor in multivariate analysis. Experimentally, FOXC1 silencing significantly inhibited the growth and metastasis of colon cancer cells in vitro and in vivo. FOXC1 transcriptionally regulates SNAIL1, contributing to epithelial-to-mesenchymal transition and metastasis in colon cancer cells. Conclusions: Dysregulated expression of FOXC1 may play a critical role in colon cancer progression and metastasis. Thus, FOXC1 may serve as a candidate prognostic biomarker and therapeutically targeted.
The importance of fertility preservation in women with early breast cancer
Authors: A. Agbarya, S. Linn
Journal: Journal of Clinical Oncology (2009)

e20663 Background: Young women with breast cancer often seek advice regarding treatment effects on their fertility. The purpose of this study was to gain a better understanding of women's attitudes to fertility and how these concerns affect decision-making. Methods: A survey on fertility issues was developed for young women with a history of early-stage breast cancer. The survey was completed by direct interviews with the patients. Results: Eighty-four eligible respondents completed the survey. Mean age at breast cancer diagnosis was 34.7 years. Fifty-seven percent of the women were Jewish and 43% were Arabic; 71% were married; 75% had more than 12 years of education. Stages at diagnosis were: I - 51%; II - 38%; III - 11%. Seventy-seven percent of the women were within six months of diagnosis and 49% reported substantial concern about becoming infertile with treatment. In multivariate logistic regression, a greater concern about infertility was associated with a wish for children (p=0.0008), number of children less than three (p=0.001), more than 12 years of education (p=0.004), and a moderate or high level of fear of treatment (p=0.004). Seventy-nine percent of patients reported discussing fertility concerns with their doctors, and 14% underwent a medical procedure for fertility preservation. Only five patients stated that infertility concerns influenced their treatment decisions. Conclusions: 1. Fertility after treatment is a major concern for young breast cancer patients undergoing chemotherapy. 2. This statement was not affected by ethnicity. 3. There is a need to communicate with and educate young patients regarding fertility issues and large scale future research directed at preserving fertility for young breast cancer survivors is warranted. No significant financial relationships to disclose.
Differential Modification of Development of Preneoplastic Lesions in the Syrian Golden Hamster Initiated With a Single Dose of 2,2′-Dioxo-&lt;italic&gt;N&lt;/italic&gt;-nitrosodipropylamine: Influence of Subsequent Butylated Hydroxyanisole, α-Tocopherol, or Carbazole&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: Malcolm A. Moore, Hiroyuki Tsuda, Witaya Thamavit, Tsuneo Masui, Nobuyuki Ito
 7
Journal: JNCI Journal of the National Cancer Institute (1987)

The effects of butylated hydroxyanisole [(BHA) CAS: 25013-16-5], alpha-tocopherol [(TC) CAS: 59-02-9], and carbazole [(CA) CAS: 86-74-8] administered subsequent to a single dose of 2,2'-dioxo-N-nitrosodipropylamine [(DOPN) CAS: 60599-38-4] on the development of putative preneoplastic lesions were investigated in Syrian golden hamsters. Whereas the 2 antioxidants BHA and TC inhibited the incidence of both liver and pancreatic lesions, CA, itself giving rise to considerable numbers of enzyme-altered foci, enhanced carcinogenesis in the liver while inhibiting carcinogenesis in the pancreas. All 3 of these agents induced hyperplastic and papillomatous lesions in the forestomachs of treated animals, independent of prior DOPN treatment; these forestomach lesions were not evident in controls. Cellular atypia and invasive growth characteristics signifying malignant change were also observed in BHA-induced forestomach lesions. The results demonstrate that hepatocarcinogenesis in the Syrian golden hamster, like that in the rat, can be inhibited by antioxidants. The similar decrease in putative preneoplastic lesion yield evident in the pancreas of BHA- or TC-treated hamsters, considered in the light of similarities in altered enzyme phenotype in carcinogen-induced lesions of both organs, suggests that common biochemical changes can be an underlying factor in the modification of neoplastic development in liver and pancreas. The present results also provide further evidence that CA has carcinogenic potential for the liver and forestomach of experimental animals.
IL-4 promotes asymmetric dimethylarginine accumulation, oxo-nitrative stress, and hypoxic response–induced mitochondrial loss in airway epithelial cells
Authors: Bijay Pattnaik, Manish Bodas, Naveen Kumar Bhatraju, Tanveer Ahmad, Richa Pant, Randeep Guleria, Balaram Ghosh, Anurag Agrawal
Journal: Journal of Allergy and Clinical Immunology (2016)
Waterfall plots provide detailed information on magnitude of response to conventional chemotherapy in advanced colorectal cancer (ACRC) - lessons learned from N9741
Authors: M. E. Campbell, A. Grothey, D. J. Sargent, R. M. Goldberg
Journal: Journal of Clinical Oncology (2007)

4080 Background: Waterfall plots have been used to capture the anti-tumor efficacy of both biologic agents (Ratain JCO 2006), which mainly exhibit a cytostatic effect, but also of chemotherapeutic agents. We are not aware of an application to therapeutic studies in CRC. We conducted waterfall plot analyses on the data of N9741 which compared IFL, FOLFOX4, and IROX as first-line therapy in ACRC (Goldberg JCO 2004). Methods: 634 (IFL 215, FOLFOX 215, IROX 204) of the 795 pts presented in the published analysis had measurable disease, and are included. The percentage change in tumor measurements from baseline to 12 wks was calculated, allowing for a time window of assessment from 6 to 20 wks for those without a 12 wk measurement. Pts with progression before the 12 wk assessment were assigned a 100% increase. The average reduction in tumor burden (ARTB) was calculated as difference in waterfall AUC divided by the number of pts. ARTB captures the average percentage reduction in tumor measurements at 12 wks for a patient entering the trial. Results: Waterfall plot analysis demonstrated some tumor growth at 12 wks in 23.7% (IFL), 15.8% (FOLFOX), and 26.9% (IROX) of pts. In contrast, tumor shrinkage was observed in 67.9% (IFL), 71.6% (FOLFOX), and 61.4% (IROX) of pts. Total differential AUC was -34.4 (IFL), -61.6 (FOLFOX), and -30.4 (IROX) resulting in an ARTB of 16.0% (95% Confidence Interval (CI) (23.7%, 8.2%)) for IFL, 28.7% (35.1%, 22.2%) for FOLFOX, and 14.9% (22.5%, 7.3%) for IROX. Conclusions: Waterfall plot analyses are feasible in this and likely other CRC trials using conventional chemotherapy. Our analysis confirms the published results of N9741, but suggests a larger degree of benefit for individuals based on anti-tumor activity than captured by conventional response analysis. Waterfall plots provide a potentially useful new efficacy metric, the average reduction of tumor burden per pt, which should be validated in future trials. No significant financial relationships to disclose.