tbuckley/cabot-search huggingface dataset:
PSMA activation of antifolate prodrugs for treatment of prostate cancer
Authors: Tatiana Litvin-Vechnyak, Natalia Lavnikova, Emine Abali, Zhenghong Peng, William Bornmann, Joseph Bertino
Journal: Cancer Research (2007)

5732  	Efficacy of chemotherapy in the treatment of prostate cancer is limited and is associated with systemic toxicity. The present study was aimed at developing a targeted prodrug therapy that would exploit the enzymatic properties of the prostate specific membrane antigen (PSMA), a glutamate carboxypeptidase that is over-expressed in prostate cancer cells and the vascular endothelium of many cancers, to activate a non-toxic prodrug folate antagonist, specifically at the tumor site thereby diminishing systemic toxicity.  	Preliminary studies using methasquin, a potent dihydrofolate reductase inhibitor, and pemetrexed (PTX), a multitargeted antifolate that is a potent thymidylate synthase inhibitor, and as well an inhibitor of dihydrofolate reductase and glycine amido nucleotide formyl transferase, confirmed that these compounds are potent cytotoxic agents against human prostate cancer cell lines. Prodrugs of methasquin and pemetrexed with one to five additional amino acids both in the alpha or gamma carboxyl linkage were synthesized and tested as substrates for PSMA. Using cytotoxicity and clonogenic assays we identified two candidate pemetrexed prodrug compounds that were more selective against LNCaP and the CWR22 cell lines, expressing PSMA, than PC-3 and DU145 cell lines not expressing PSMA. An inhibitor of PSMA, quisqualic acid, reversed the sensitivity of PSMA (+) cells to these prodrugs further confirming the PSMA-dependent cytotoxic effect on LNCaP and the CWR22 cells. The prodrugs were shown to be stable in human and mouse plasma for >18 hours. Currently LNCaP cells stably expressing siRNAs that effectively knock-down PSMA are being generated. Transient knock-down of PSMA has previously been achieved using the same siRNA oligo sequences. The identified prodrugs will be further evaluated in mouse xenogfraft models, and if promising, in patients with prostate cancer.
Estrogen receptor-positive, progesterone receptor-negative tumors: Pathology and outcome correlations from a single-center cohort.
Authors: Oana Cristina Danciu, Jigisha P. Thakkar, Divyesh Mehta
Journal: Journal of Clinical Oncology (2012)

160 Background: Estrogen receptor (ER) + progesterone receptor (PR) - tumors are a distinct subset of breast cancers characterized by aggressive behavior and tamoxifen resistance in spite of being ER+. We sought to describe the characteristics of the patients treated for this type of breast cancer at a large, urban, academic center, compare them with ER+PR+ patients and evaluate the outcomes achieved with the current modern treatments and establish the predictors of worse outcomes. Methods: All patients with the diagnosis of breast cancer who underwent a biopsy at our center between January 1st, 2005 and December 31st 2010 were included into a database. We compared ER+/PR- with ER+/PR+ patients. Demographic data, comorbidities, obstetric data, pathology data, type of treatment and outcome data were collected retrospectively through extensive electronic medical records review. The study was approved by the local IRB. Standard statistical methods were used and a p value &lt;0.05 was considered significant. Results: We found 101 ER+/PR- and 150 ER+/PR+ breast cancer patients. Baseline characteristics, pathology data, treatment and outcomes are shown in the table. Within the ER+/PR- group the degree of Ki67 expression was directly associated with recurrence rate (p 0.0039). Conclusions: ER+/PR- breast cancer is an aggressive type with high recurrence rate and mortality, that affects mainly postmenopausal women. This subtype is associated more frequently with p53 and Ki67 overexpression, and the later levels appear useful in predicting recurrence in this subtype of breast cancer. Novel treament paradigms guided by molecular studies are currently being implemented. [Table: see text]
Effect of Infection With Moloney Sarcoma and Leukemia Viruses on Nucleic Acid Synthesis in Mouse Cell Cultures
Authors: S Z Hirschman, P J Fischinger, T E O'Connor
Journal: JNCI Journal of the National Cancer Institute (1970)

Journal Article Effect of Infection With Moloney Sarcoma and Leukemia Viruses on Nucleic Acid Synthesis in Mouse Cell Cultures Get access Shalom Z. Hirschman, Shalom Z. Hirschman Molecular Virology Section, Viral Leukemia and Lymphoma Branch, National Cancer Institute,3Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Peter J. Fischinger, Peter J. Fischinger Molecular Virology Section, Viral Leukemia and Lymphoma Branch, National Cancer Institute,3Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Timothy E. O'Connor Timothy E. O'Connor Molecular Virology Section, Viral Leukemia and Lymphoma Branch, National Cancer Institute,3Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 44, Issue 1, January 1970, Pages 107–116, https://doi.org/10.1093/jnci/44.1.107 Published: 01 January 1970 Article history Received: 19 May 1969 Accepted: 23 September 1969 Published: 01 January 1970
Ixabepilone (BMS-247550) and metastatic renal cell carcinoma (mRCC)
Authors: H. Huang, M. E. Menefee, M. Edgerly, H. Kotz, M. Poruchynsky, W. D. Stein, S. E. Bates, A. T. Fojo
Journal: Journal of Clinical Oncology (2008)

5053 Background: Ixabepilone, a semi-synthetic analog of the natural product epothilone B, is a non-taxane microtubule-stabilizing agent active against cancers insensitive to paclitaxel. This phase II trial assessed the activity of ixabepilone in mRCC. Methods: 87 patients with mRCC received 6 mg/m2/day ixabepilone IV for 5 successive days and were restaged every 2 cycles. Tissue was obtained before and after treatment in cycle 1 to evaluate target engagement. Results: Histologic subtypes included 74 clear cell, 3 mixed clear cell with other, 5 papillary and 5 other. Although 78 (90%) had prior nephrectomy, patients had extensive disease at time of enrollment with a median of 20.1 cm (range 2.0 - >50 cm) of measurable disease by RECIST. Overall RR was 12.6% (one CR and 10 PR) with a median shrinkage of 12% in the 37% of patients with measurable shrinkage. Median response duration, 5.5 months; median number of cycles, 5; median duration of treatment, 18.4 weeks. Treatment-related AE primarily G1/2. Median ANC nadir only 2718. Treatment-related neuropathy predominantly sensory and mild to moderate. Microtubule stabilization was demonstrated in 84 to 92% of serial biopsies. Median overall survival (OS) of Motzer 0/1 pts with clear cell histology was 19.25 months on ixabepilone. This can be compared with 19.3 and 15.9 months in the treatment and placebo groups of the sorafenib registration trial and 15 months in 40 mRCC patients previously treated with placebo at NCI. We also developed and validated a two-phase equation to estimate the concomitant rates of tumor regression (regression rate constant) and tumor growth (growth rate constant) using tumor measurements gathered while patients received therapy, and demonstrated a correlation of the growth rate constant with OS. Using this analysis we demonstrated that, compared to mRCC patients previously treated with placebo at NCI, ixabepilone reduced the growth rate constant of mRCC by 2-fold. Conclusions: Ixabepilone is a potent microtubule-stabilizing agent active in mRCC where it both induces tumor regression as well as growth retardation and prolongs OS. This active cytotoxic agent should be considered in combination with novel targeted therapies in future studies. No significant financial relationships to disclose.
Osteosarcoma recurrences in pediatric patients previously treated with intensive chemotherapy.
Authors: M D Tabone, C Kalifa, C Rodary, M Raquin, D Valteau-Couanet, J Lemerle
Journal: Journal of Clinical Oncology (1994)

Between January 1981 and June 1993, 137 children and adolescents were each treated at the Institut Gustave Roussy for an initially nonmetastatic osteosarcoma of the extremities. We report the retrospective analysis of 42 cases of recurrence that occurred in this population.The median interval between the diagnosis of the primary osteosarcoma and the first recurrence was 21 months (range, 5 to 60). The site of the first recurrence was limited to the lung in 20 patients, the bone in seven patients, was local in six patients, and was confined to soft tissue in one patient. In eight patients, the first recurrence affected multiple sites. Subsequent recurrences often involved unusual or multiple sites. Management of recurrences included surgery and/or various regimens of second-line chemotherapy, and in one case involved high-dose chemotherapy followed by autologous bone marrow transplantation. Overall survival and event-free survival were, respectively, 36% and 27% at 36 months. At present, 13 patients are alive without evidence of disease. Response of the primary tumor to preoperative chemotherapy, the time between the diagnosis and the first recurrence, and the number of metastatic lesions did not correlate with survival. The survival rate is better in patients with a local or a pulmonary first recurrence.The most important prognostic indicator at first recurrence seems to be the possible complete resection of disease. Patients not amenable to surgery and patients with a second or a third recurrence have a poor prognosis. The potential benefit of more aggressive treatments such as high-dose chemotherapy and autologous bone marrow transplantation should be investigated for these patients.
Click‐Crosslinked Injectable Gelatin Hydrogels
Authors: Sandeep T. Koshy, Rajiv M. Desai, Pascal Joly, Jianyu Li, Rishi K. Bagrodia, Sarah A. Lewin, Neel S. Joshi, David J. Mooney
Journal: Advanced Healthcare Materials (2016)

Injectable gelatin hydrogels formed with bioorthogonal click chemistry (ClickGel) are cell-responsive ECM mimics for in vitro and in vivo biomaterials applications. Gelatin polymers with pendant norbornene (GelN) or tetrazine (GelT) groups can quickly and spontaneously crosslink upon mixing, allowing for high viability of encapsulated cells, establishment of 3D elongated cell morphologies, and biodegradation when injected in vivo. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Upholding Family-Centered Care in the Face of High-Consequence Pathogens—Thinking Inside the Room—Reply
Authors: Preeti Mehrotra, Andi L. Shane, Aaron M. Milstone
Journal: JAMA Pediatrics (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Results of an AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica) Randomized Clinical Trial in Children with Low- and Intermediate-Risk Relapsed Acute Lymphoblastic Leukemia (ALL)
Authors: Franco Locatelli, Marco Zecca, Gianni Cazzaniga, Luciana Vinti, Andrea Biondi, Tommaso Mina, Chiara Messina, Rosanna Parasole, Franca Fagioli, Ottavio Ziino, Giuseppe Basso, Riccardo Masetti, Carmelo Rizzari
Journal: Blood (2014)
French experience of patient management when receiving oral vinorelbine chemotherapy (NVBO) for metastatic breast cancer: Final results of a prospective observational survey on practices
Authors: J. Lotz, F. Husseini, M. Finck, M. Rotarski, L. Bastit, A. Riviere, A. Youssef, J. Mouysset, S. Nahon, V. Piolat
Journal: Journal of Clinical Oncology (2009)

e12013 Background: An observatory on practices has been implemented in France with the aim of investigating the correlation between patient (pt) profile and the use of an oral chemotherapy (OCT), NVBO. Methods and Materials: Three questionnaires were used: a “Physician” questionnaire (medical practice conditions, role of OCT), a “Patient” questionnaire (pt disease history, prescription selection factors and compliance), and a Patient Preference self-questionnaire (partly based on the EORTC QLQ-BR23). Results: Between February 06 and February 08,355 pts were enrolled in 47 centers. Breast tumours were classified as having limited aggressiveness with or without visceral metastasis (41.2%) or slowly progressing visceral metastasis and DFI&gt;24 months (42.3%) or aggressive disease with visceral metastasis and DFI&lt;12 months (16.5%). Pts had previously received hormonotherapy in 72.4%, iv CT in 78.6% and OCT in 31%. NVBO was prescribed as monotherapy in 53,6% and association in 46,4%, with iv in 35% (66.7% with trastuzumab), with oral in 65% ( 97.2% with capecitabine ). 86.2% of pts preferred OCT for 3 main reasons : more time with their family, social life maintained and treatment at home. Physicians’ major parameters of OCT choice according to score (1 to 4) were : patient-related factors (QOL 3.61), reduced hospital stays (2.99) and problems related to venous administration (2.62). Conclusion: NVBO brings added value in terms of pt convenience allowing improved QOL and reduced hospital stays while keeping optimal compliance to treatment schedule. [Table: see text]
Oral topotecan demonstrates clinical activity in relapsed non-small cell lung cancer. Results from an open-label, phase III study (387) comparing oral topotecan to intravenous docetaxel
Authors: R. Ramlau, R. Gervais, M. Krzakowski, J. von Pawel, E. Kaukel, R. Abratt, B. Dharan, G. Ross, G. Dane, F. Shepherd
Journal: Journal of Clinical Oncology (2005)

7017
Management of complicated tumor response (CTR) to tyrosine kinase inhibitors (TKI) in gastrointestinal stromal tumor (GIST) patients (pts) with locally advanced/metastatic disease
Authors: P. Coco, E. Fumagalli, C. Morosi, A. Messina, R. Bertulli, S. Stacchiotti, A. Gronchi, P. Casali
Journal: Journal of Clinical Oncology (2009)

e21512 Background: Bleeding, perforation, and infection may complicate TKI therapy in GIST. Their incidence and best management are not completely known yet. Methods: Between May 2001 and December 2008, 278 pts were treated with imatinib or sunitinib, respectively, as first or second line therapy. Pts experienced bleeding, perforation and colliquation with superimposed infection were recorded and reviewed. Results: CTR occurred in 24 pts (9%) after a median time of 241 days from treatment start (8–2090 days). In 5 pts the complication took place after increasing the dose. Before complication, according to RECIST criteria, a partial response (PR) and a stable response (SD) were respectively documented in 16 and 8 pts . Radiologically assessed bleeding in closed lesions was seen in 13 pts (5%). All but one were treated conservatively with supportive care and blood transfusions. The other pt required surgical resection of his peritoneal bleeding lesion. Nine pts (3%) developed colliquation with bacterical superinfection: 5 were treated with antibiotics, 4 had their lesions drained. Two pts underwent emergency surgery due to perforation with a superimposed infection. In 21 out of 24 pts the event resolved without sequelae. Three pts died: 2 developed massive haemorrhage, 1 had a bowel perforation. After stopping treatment for a median interval of 10 days (2–63), all but one restarted treatment at the previous dose. No further complications were seen after the first event. Eight pts are still on treatment with a SD, 2 pts switched to a second line therapy due to progressive disease (PD), 11 died due to PD. Conclusions: Bleeding, perforation and colliquation with superimposed infection may occur at different time intervals from treatment start. Even if supportive care and medical therapy are successful in most of cases, pts should be carefully monitored because these complications can be life-threatening. Surgery should be considered in case of failure of conservative treatment. Reintroduction of the therapy at the same dose is feasible and well tolerated. [Table: see text]
SWOG 0222: A phase II study of tirapazamine (NSC-130181, TPZ)/cisplatin/etoposide (PE) and concurrent thoracic radiotherapy (TRT) for limited stage small-cell lung cancer (LSCLC)
Authors: Q. Le, J. Moon, M. Redman, S. K. Williamson, P. N. Lara, Z. Goldberg, L. Gaspar, J. J. Crowley, D. F. Moore, D. R. Gandara
Journal: Journal of Clinical Oncology (2008)

7523 Background: Tumor hypoxia reduces the efficacy of chemo-radiation. TPZ, a hypoxic cell cytotoxin, potentiates the effectiveness of RT and chemotherapy in preclinical models. A SWOG pilot study (S0004) showed that the combination of TPZ, PE and TRT yielded a promising median survival of 22 months. Here we report results of the phase II study designed to confirm this promising result. Methods: The concurrent phase consisted of 2 cycles of P (50 mg/m2, d1, 8, 29, 36) and E (50 mg/m2 d1–5, 29–33) and once-daily TRT (1.8–2 Gy/fx, 61 Gy). TPZ was given at 260 mg/m2 on d1, 29 and at 160 mg/m2 on d8,10,12, 36, 38 and 40. Consolidation consisted of 2 cycles of P (60 mg/m2) and E (120 mg/m2, d1–3) on wk 11 and 14. Patients with a complete response received prophylactic cranial irradiation. Statistical design: Considered promising if the median survival were ≥ 21 mo and of no further interest if ≤ 14 mo. Results: S0222 was closed early due to a report of excess toxicity for TPZ in a head and neck cancer trial elsewhere. 69 of the planned 85 patients were accrued. Median age: 63; PS0/1: 39/29. Of 67 patients evaluable for toxicity during the concurrent phase, 16 (24%) had grade 3–4 esophagitis and 8 (12%) had grade 3 febrile neutropenia. There were 3 possible treatment related deaths, 2 in the concurrent phase (1 progressive disease NOS within 30 days, 1 pericardial effusion) and 1 in the consolidation phase (esophageal hemorrhage). Response rate from concurrent phase: 63%; 18% had inadequate response assessment and are included as non-responders. At a median follow up of 20 months, median progression-free survival is 12 mo (95% CI: 10–13 mo) and median overall survival is 23 mo (95% CI: 17–33 mo). Major toxicities and outcomes for S0004 and S0222 are compared below. Conclusions: S0222 and S0004 showed acceptable levels of toxicity with comparable rates of grade 3–4 toxicities and similar promising median survivals. Further study of hypoxia-targeted therapy is warranted in LSCLC. Comparison of toxicities, major response rates and median survival for S0222 and S0004 Grade 3–4 toxicities(concurrent phase only) Pilot study: S0004 N (%) Phase II study: S0222 N (%) Patients 29 67* Neutropenia 16(55%) 41(61%) Febrile Neutropenia 4(14%) 8(12%) Infection with Gr 3–4 Neutropenia 2(7%) 3(4%) Vomiting 10(34%) 8(11%) Esophagitis 10(34%) 16(24%) Pneumonitis 0(0%) 1(1%) Response rate 80% 63%** Median survival 22 months 23 months * Evaluable patients for toxicity; ** 18% of patients had inadequate response assessments No significant financial relationships to disclose.
추계학술대회 초록집 : GSK 후원 해외연수 연구보고 ; 간세포암종에서 Raf kinase inhibitor protein의 역할
Authors: 이한주 ( Han Chu Lee )
Journal: Clinical and Molecular Hepatology (2006)

목적: 간세포암종에서는 insulin-like growth factor (IGF) 신호전달경로의 이상 조절이 흔히 관찰된다. 최근 Raf kinase inhibitor protein (RKIP)이 유사분열물질에 의한 ERK/MAPK 경로의 활성화를 억제하는 내인성 물질이라는 사실이 밝혀졌고, 전립선암과 악성 흑색종에서 RKIP의 발현 저하가 종양의 전이, 이동성과 밀접히 관련이 있다는 사실이 밝혀졌다. 이에 저자들은 간세포암종 조직에서 RKIP 발현의 변화 유무와 RKIP 발현 저하가 간세포암종 세포주에 미치는 영향을 밝히고자 본 연구를 시행하였다. 대상과 방법: 총 17쌍의 간세포암종 및 그 주변 조직에서 면역조직화학염색법을 시행하여 RKIP 단백 발현의 정도를 비교하였고, 8쌍의 조직에서는 Western blot analysis를 시행하여 이를 확인하였다. RKIP의 발현 정도가 간세포암종 세포주에 미치는 영향을 평가하기 위하여 RKIP plasmid 또는 small interfering RNA를 이입함으로써 ERK/MAPK 경로에 미치는 영향 및 세포의 증식, 이동성에 미치는 영향을 평가하였다. 결과: 17쌍의 간세포암종 조직 중 14쌍에서 암 조직에서의 RKIP 발현 저하가 관찰되었으며, RKIP 발현이 저하된 조직에서는 phospho-ERK의 발현 증가가 관찰되었다. 대조 FOCUS 세포에서는 IGF-I으로 자극하였을 때, phospho-ERK의 증가와 세포의 증식 및 이동성이 증가하는 반면, RKIP plasmid의 이입은 이러한 효과를 감소시켰다. 반대로 small interfering RNA로 RKIP의 발현을 억제시킨 HepG2 세포에서는 IGF-I 자극 후 Raf kinase의 활성도 및 phospho-ERK의 증가가 더 현저하게 관찰되었다. 결론: RKIP의 발현은 간세포암종에서 감소되어 있고, RKIP 발현의 감소는 IGF-I에 의한 ERK/MAPK 경로의 활성화와 관련이 있다. 인위적으로 RKIP의 발현을 증가시키면 이러한 변화를 억제시킬 수 있으며 결과적으로 암 세포의 증식과 이동성 증가를 억제시킬 수 있다.
Thioacetamide 에 의한 간경변에서 Pentoxifylline 투여가 흰쥐의 간 섬유화와 세포주기조절 단백질에 미치는 영향
Authors: 장기택(Kee Taek Jang), 이미숙(Mee Suk Lee), 정인평(In Pyung Jung), 김미란(Mee Ran Kim), 장자준(Ja June Jang)
Journal: Clinical and Molecular Hepatology (2001)

Badqpound: Thioacetamide is a classic hepatotoxic reagent which leads to the reproducible hepatic fibrosis in rats. oacetamide-induced fibrosis is an appropriate model for cirrhosis in humans due to the long duration of course and similiar histology. Thioacetamide prmhxes hepatotoxicity through lipid peroxidation but it is unclear whether lipid peroxidation directly correlated with hepatic fibrosis. Pentoxifylline, a derivative of the methylxanthine, showed an antifibrogenic effect in cell cultures of human fibroblasts and some animal models. But this antifibrogenic effect is controversial. Pentoxifylline revealed a hepatoprotective effect in some toxic hepatitis. This hepatoprotective effect seems to influence cell cycle regulatory protein during regeneration. This study aimed to evaluate an effect of pentoxifylline on fibrosis and cell cycle regulatory protein during liver regeneration in thioacetamide-induced rat cirrhosis. Lipid peroxidation assay was compared with collagen content so as to evaluate the correlation with fitxosis. Mcttmd: Liver cirrhosis was induced by 0.03Yo oral administration of thioacetamide. Pentoxifylline was administered simultaneously with thioacetamide, The semiquantitative fibrosis index was measured based on histologic finding. Collagen content was estimated by spectrophotometric assay. Activated hepatic stellate cells were counted using a -SMA immunohistochemistry. Malondialdehyde, lipid peroxidation metabolite, was estimated by thiobarbituric acid reactive substance assay. Cell cycle regulatory protein was evaluated by western blot. Results- There was no difference in semiquantitative fibrosis index, collagen content and hepatic stellate cell count between thioacetamide treated rats and simultaneous pentoxifylline treated rats. Lipid peroxidation product was not correlated with collagen content. Western blot showed no difference in cell cycle regulatory protein. Conclusion- Pentoxifylline does not show an antifibrogenic effect in thioacetamide-induced rat cirrhosis, in which thioacetamide induced hepatocellular damage and fibrosis. Lipid peroxidation may be a secondary effect rather than prirrmy mediating mechanism in hepatic fibrosis. (Karean J ERafol 20017:281-291)