tbuckley/cabot-search huggingface dataset:
OC-007 Risk of complications in a Scottish Crohn's disease cohort and association with disease location
Authors: A M Phillips, M C Aldhous, N Lewin-Koh, H E Drummond, L Smith, S McLeod, S Pidasheva, C Mowat, H Clark, J Satsangi
Journal: Gut (2010)

<h3>Introduction</h3> Risk of complications in Crohn9s disease (CD) is substantial but varies according to age at onset, smoking and possibly disease location. We examined a well characterised cohort of Scottish CD patients to explore how disease location modified time to first resection and time to complications. <h3>Methods</h3> Consenting CD patients attending GI clinics in Edinburgh and Dundee participated. Patients9 disease behaviour was documented according to the Montreal classification. First surgical resection was defined as the first operation removing a portion of intestine, excluding simple appendicectomies or defunctioning procedures. Time to complication was defined as the time from diagnosis to the first stricturing or internally penetrating complication. <h3>Results</h3> 1150 patients were recruited, of which full phenotypic data were available in over 95%. The median age at onset was 28.6 years (IQR 21.2–43.1) with 10.2% A1, 60.6% A2 and 29.2% A3. The median length of follow-up was 10.3 years (IQR 4.1–19.8 years). The maximum Montreal location was L1 in 27.9%, L2 in 35.2%, L3 in 24.4%, pure L4 in 2% and L4 plus another location in 10.5%. On Kaplan Meier analysis the median time to first resection was 8.9 years (95% CI 7.5 to 10.1). At 20 years following diagnosis only 31% of patients were resection free. On Kaplan–Meier analysis the median time to first complication was 14.5 years (95% CI 10.5 to 19.5 years), and at 20 years 45% of patients were without complication. Cox proportional hazards models were used to examine disease location with respect to time to first resection and time to first complication, adjusting for age at diagnosis and smoking status at diagnosis as necessary. When compared to the average risk of resection in the population studied, pure colonic disease had an HR for resection of 0.45 (95% CI 0.41 to 0.49) whereas pure ileal disease had an HR of 2.55 (95% CI 1.96 to 1.62). Ileocolonic disease conferred an intermediate risk of 1.23 (95% CI 0.93 to 1.62). When compared to the average risk of complication in the population, pure colonic disease conferred an HR of 0.34 (95% CI 0.34 to 0.34). Pure ileal disease conferred an HR of 1.87 (1.37 to 2.54). Ileocolonic disease had an intermediate HR of 1.17 (95% CI 0.84 to 1.63). <h3>Conclusion</h3> This study, while confirming that colonic disease confers a lower risk of surgery and complications than other disease locations, also suggests that the risks are greater in pure ileal disease when compared with ileocolonic disease. Clinicians making treatment decisions should take CD location into account.
Living With Cancer: Assessing The Educational, Symptomatic, and Quality Of Life Impact Of a Comprehensive Patient Symposia On Cancer Patients
Authors: Leslie J Padrnos, Amylou Constance Dueck, Robert M. Bennett, Robyn M. Emanuel, Ruben A. Mesa, Donald Northfelt, Joseph R. Mikhael, Pamela Glassley, Rachel Stigge, Annette Aguirre
Journal: Blood (2013)
Use of Transarterial Chemoembolization (TACE) and Sorafenib in Patients with Unresectable Hepatocellular Carcinoma: US Regional Analysis of the GIDEON Registry
Authors: Jean-Francois H. Geschwind, Pierre M. Gholam, Alec Goldenberg, Parvez Mantry, Robert C. G. Martin, Bilal Piperdi, Ellen Zigmont, Joanne Imperial, Svetlana Babajanyan, Pamela K. Foreman, Allen Cohn
Journal: Liver Cancer (2015)

Global Investigation of Therapeutic Decisions in Hepatocellular Carcinoma and of Treatment with Sorafenib (GIDEON) is a worldwide, prospective, non-interventional study to evaluate the safety of sorafenib in a variety of patient subsets.Eligible patients had unresectable hepatocellular carcinoma for whom the decision had been made to treat with sorafenib. Treatment strategies were instituted at the physician's discretion. Patient and disease characteristics, treatment practices, incidences of adverse events (AEs), and overall survival were collected.In the United States, 563 patients were evaluable for safety. Subgroup analysis was performed for patients who underwent transarterial chemoembolization (TACE) prior to the initiation of sorafenib (group A, n=158), after the initiation of sorafenib only (group B, n=29), both (group C, n=38), or did not undergo TACE (n=318). Patient demographics were similar across the groups. In group A, 29% had Child-Pugh score B or C at diagnosis, and 19% had Barcelona Clinic Liver Cancer tumor stage C or D. In group B, 48% had Child-Pugh score B or C at study entry, and 31% had BCLC stage C or D. The majority of patients in all groups initially received full-dose sorafenib. Incidences of grade ≥3 drug-related AEs were 30%, 17%, and 16% in groups A, B, and C, respectively, and 22% in patients who did not undergo TACE. No new safety signals emerged.The results from GIDEON reaffirm that sorafenib can be safely used in the context of TACE.
Updated results of a phase II trial integrating gefitinib (G) into concurrent chemoradiation (CRT) followed by G adjuvant therapy for locally advanced head and neck cancer (HNC)
Authors: S. M. Ahmed, E. E. Cohen, D. J. Haraf, K. M. Stenson, E. Blair, B. E. Brockstein, S. Lin, E. Lester, A. Dekker, R. Williams, E. E. Vokes
Journal: Journal of Clinical Oncology (2007)

6028 Background: This study was undertaken to evaluate the tolerability and efficacy of substituting G for paclitaxel into a well- described CRT regimen (Clin Cancer Res 9: 5936; JCO 21: 320) and continuing G as adjuvant therapy. Endpoints included complete response (CR) rate to CRT, progression-free (PFS), disease-specific (DSS) and overall survival (OS), and local &amp; distant control rates. Methods: Previously untreated subjects with stage III, IVa, or IVb squamous cell, poorly differentiated carcinomas, or lymphoepithelioma were enrolled. Organ sparing surgery was allowed. Subjects received 2 cycles of carboplatin/paclitaxel induction followed by CRT with G (250 mg PO qd), 5- fluorouracil, hydroxyurea, and twice daily radiation on day 1–5 of five 14d cycles. G was continued for 2 years from the start of CRT. Results: From 2/03 to 10/04, 67 eligible subjects accrued including 51 males; median age 56; ECOG PS 0 in 47, 1 in 19, and 2 in 1; stage IV in 61 (91%). With median follow-up of 858 days, 9 have had progressive disease (PD, 3 distant, 5 local, 1 with both) and 15 have died (12 related to HNC). Estimated OS=83% at 2y, 73% at 3y; PFS=77% at 2y, 64% at 3y; and DSS=86% at 2y, 80% at 3y. In 56 evaluable subjects we observed 51 CR (91 %), 4 partial responses and 1 PD after CRT. Non-evaluable subjects underwent surgery prior to CRT (10), or died prior to evaluation (1). Grade 3/4 toxicity included mucositis (75%/10%), dermatitis (29%/3%), rash (4%/0%) and diarrhea (1%/0%). Sixty-two patients received maintenance gefitinib, with 60 reliably reporting doses (median days on gefitinib=667). Reasons for holding G included LFT abnormalities, patient refusal, diarrhea, rash, recurrence, hospitalization for acute illness, and early death. Conclusions: Adding G to concurrent CRT after induction therapy, and as adjuvant therapy is tolerable and feasible. Favorable survival and CR data suggest that this is a promising regimen for patients with locally advanced HNC. [Table: see text]
Efficacy of a combination chemotherapy regimen with dose-dense paclitaxel and gemcitabine in heavily pretreated metastatic breast cancer patients including anthracyclines and docetaxel.
Authors: M. A. Pluma Jimenez, J. A. Gutierrez, Y. L. Bautista Aragon, A. J. Silva, R. Villalobos, S. Rivera, M. Perez
Journal: Journal of Clinical Oncology (2010)

e11518 Background: Metastatic breast cancer is a heterogeneous disease. Anthracyclines and taxane based regimens are the most active in this disease, with few treatment options after failure of this agents. Dose-dense chemotherapy with paclitaxel has proven to be more effective than the 3-weekly schedule. Methods: We evaluated the efficacy and tolerance of weekly-paclitaxel (70 mg/m2 weekly for 12 consecutive weeks) combined with gemcitabine (800 mg/m2 on days 1 and 8 every 3 weeks) in heavily pretreated patients (anthracyclines, docetaxel, capecitabine and vinorelbine) with metastatic breast cancer. Results: From March 2008 to July 2009 16 patients received this regimen. The median age was 42 years (range 31-68), 15 patients had an ECOG performance status 1 (94%), ER and/or PR receptor status was positive in 8 patients (50%), c-erb-B2 status was negative in 15 patients (94%). 12 patients (75%) had received anthracyclines and 5 patients (31%) had received docetaxel in the neo/adjuvant setting. The median number of chemotherapy regimens received for metastatic disease was 1 (range 0-5). 7 patients (43%) had received ≥ 2 regimens for metastatic disease. 8 patients (50%) had visceral metastases and 12 patients (75%) had ≥ 2 metastatic sites. The median duration of treatment with this regimen was 14 weeks (range 4-24). The overall response rate was 44%, stable disease was 14%, and progressive disease was 42%. Median time to disease progression was 5.5 months. Grade 3-4 hematologic toxicity was observed in 2 patients (13%), peripheral neurologic toxicity was observed in 6 patients (38%), 5 with grade 1-2. Treatment delay and/or dose reduction occurred in 4 patients (25%). Conclusions: Combination chemotherapy with dose-dense paclitaxel and gemcitabine is a highly active regimen and has an acceptable toxicity profile in heavily pretreated metastatic breast cancer patients including patients previously treated with taxanes. This results suggest that this regimen should be further explored in clinical trials. No significant financial relationships to disclose.
Current status of a phase III trial of nimotuzumab (ti-EGF-R) in newly diagnosed glioblastoma.
Authors: F. Bach, M. Westphal
Journal: Journal of Clinical Oncology (2011)

2059 Background: The receptor for epidermal growth factor (EGF-R) has been one of the first molecules suspected to have a role in the glioma disease. Within the CNS it has exquisite selectivity for high grade glioma cells. A monoclonal antibody against EGF-R (nimotuzumab) and binding more specifically to highly over expressing cells has shown promise in preclinical and early clinical findings. Methods: Nimotuzumab was tested in an open label, randomized, multicenter Phase III trial in patients with newly diagnosed glioblastoma. OSAG 101 is administered by i.v. infusion (2 weekly infusions of 400mg) during the current standard radio chemotherapy followed by biweekly infusions of 400mg thereafter until progression. Only histologically confirmed glioblastoma patients were included and stratified for resection status. Primary endpoint was time to progression as determined by centralized neuro-imaging review. Overall survival serves as a secondary endpoint with quality of life and safety as additional parameters. Results: Between August 2008 and March 2010, the targeted total study population of 150 patients was enrolled in 10 sites. A prespecified interim analysis of the first cohort of 75 patients with a minimum follow of 12 month showed no specific toxicity of nimotuzumab and an unconspicuous safety profile with no reports of rash, conjunctivitis or mucositis Efficacy still cannot be determined in this cohort with naturally small subgroups but the molecular analysis is available and indicates a statistically not significant trend related to MGMT methylation and EGF-R status PFS: non-methylated: chemoradiation vs chemoradiation + OSAG101 (5.6m vs 8.3m) OS: non-methylated chemoradiation vs chemoradiation + OSAG101 (14.5m vs. 13.8m) EGFR amplifiedOS (14.9m vs. 19.4m) EGFR non-amplified OS (10.7m vs. 13.3m) Conclusions: Nimo for newly diagnosed glioblastoma has been proven to be safe and free of additional toxicity to the standard radio chemotherapy. The interim analysis suggests that with further data maturation subgroups may emerge in which there is a differential effect of Nimo depending on MGMT status and EGF-R status.
Phase II Feasibility Study of Sequential Couplets of Cisplatin/Topotecan Followed by Paclitaxel/Cisplatin as Primary Treatment for Advanced Epithelial Ovarian Cancer: A National Cancer Institute of Canada Clinical Trials Group Study
Authors: P. Hoskins, E. Eisenhauer, I. Vergote, J. Dubuc-Lissoir, B. Fisher, R. Grimshaw, A. Oza, M. Plante, G. Stuart, J. Vermorken
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Despite the improved results in advanced ovarian cancer achieved with the addition of paclitaxel to frontline therapy, there remains room for improvement. One approach is to add new agents such as topotecan. Because myelosuppression limits the delivery of topotecan with paclitaxel/cisplatin in a three-drug combination, we explored giving sequential couplets of cisplatin/topotecan followed by paclitaxel/cisplatin. PATIENTS AND METHODS: Forty-four patients with residual epithelial ovarian carcinoma after primary surgery were studied. Cisplatin 50 mg/m 2 on day 1 and topotecan 0.75 mg/m 2 on days 1 through 5 were administered at 21-day intervals for four cycles, followed by interval debulking surgery (if optimal debulking was not achieved with primary surgery), and then paclitaxel 135 mg/m 2 over 24 hours on day 1 and cisplatin 75 mg/m 2 on day 2 at 21-day intervals for four cycles. RESULTS: Such sequential couplets are feasible. Myelotoxicity was the major toxic effect, but it was of short duration. The granulocyte nadir with topotecan/cisplatin occurred late (median, day 18), so retreatment on day 21 was not always possible. There was no unexpected nonhematologic toxicity. The regimen was active in this group of patients who had undergone largely suboptimal debulking surgery. In 34 patients with clinically measurable disease, the overall response rate was 78%, and 30 (77%) of the 39 patients with elevated CA 125 levels at baseline had normalization of CA 125 levels by the end of therapy. CONCLUSION: Sequential couplets of cisplatin/topotecan followed by paclitaxel/cisplatin are feasible. The efficacy data in this suboptimal group of patients has encouraged us to proceed with a randomized study based on this approach.
Editorial: Decernotinib: A Next‐Generation Jakinib
Authors: Massimo Gadina, Daniella M. Schwartz, John J. O'Shea
Journal: Arthritis & Rheumatology (2015)

Since the beginning of this millennium, rheumatologists have become applied cytokine biologists, taking advantage of the plethora of successful “biologics” that target cytokines for the treatment of rheumatoid arthritis (RA) and other autoimmune disorders. The mechanism of action of these agents is to block cytokines outside of the cell. However, the actions of cytokines can also be blocked by disrupting signaling pathways within the cell. This is the mechanism of action employed by a recent class of orally administered drugs, Janus kinase (JAK) inhibitors or Jakinibs. In this issue of A&R, Genovese and colleagues report the results of a Phase IIb study with decernotinib, a second generation, JAK3-selective Jakinib (1).
Natural and Experimentally Induced Antibodies to Defined Mammalian Type-C Virus Proteins in Primates2
Authors: H. P. Charman, N. Kim, M. White, H. Marquardt, R. V. Gilden, T. Kawakami
Journal: JNCI Journal of the National Cancer Institute (1975)

Using sensitive radiommunoprecipitation assays for highly purified type-C RNA tumor virus proteins, we found that 5 of 16 clinically normal gibbons (including 4 of 5 normal animals from a colony with 2 cases of lymphoma) and 4 of 4 experimentally inoculated gibbons formed antibodies to the major structural protein (p30) of gibbon ape leukemia virus (GaLV). An additional woolly monkey immunized with the closely related simian sarcoma virus also formed antibodies detectable with GaLV p30. Of 20 patients immunized with formalin-inactivated Rauscher murine leukemia virus (R-MuLV), 10 were previously reported to have antibodies to MuLV as determined by an internally labeled banded virus radioimmunoprecipitation assay. In comparison studies with purified R-MuLV proteins, 7 of 20 patients formed antibodies: 3/20 to R-MuLV p30 only, 1/20 to R-MuLV glycoprotein (gp) 70 only, and 3/20 to both p30 and gp70. Most responders were melanoma patients receiving immunotherapy with BCG. Additionally, rhesus monkeys produced antibodies to the endogenous cat virus RD114 and closely related endogenous baboon leukemia virus p30's. Thus these studies demonstrated the ability of primates (including humans) to form antibodies to well-characterized proteins from endogenous and exogenous type-C viruses and the potential utility of these assays for seroepidemiologic studies.
Physicochemical Properties and Isoenzyme Composition of Hexokinase From Normal and Malignant Human Tissues
Authors: N. K. Monakhov, E. L. Neistadt, M. M. Shavlovskii, A. L. Shvartsman, S. A. Neifakh
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Physicochemical Properties and Isoenzyme Composition of Hexokinase From Normal and Malignant Human Tissues Get access N. K. Monakhov, N. K. Monakhov 2Laboratory of Biochemical Genetics, Institute of Experimental Medicine, U.S.S.R. Academy of Medical Sciences, 197022 Leningrad 22, U.S.S.R. Search for other works by this author on: Oxford Academic PubMed Google Scholar E. L. Neistadt, E. L. Neistadt 3Laboratory of Pathology, N. N. Petrov Research Institute of Oncology, U.S.S.R. Ministry of Public Health, Leningrad, U.S.S.R. Search for other works by this author on: Oxford Academic PubMed Google Scholar M. M. Shavlovskii, M. M. Shavlovskii 2Laboratory of Biochemical Genetics, Institute of Experimental Medicine, U.S.S.R. Academy of Medical Sciences, 197022 Leningrad 22, U.S.S.R. Search for other works by this author on: Oxford Academic PubMed Google Scholar A. L. Shvartsman, A. L. Shvartsman 2Laboratory of Biochemical Genetics, Institute of Experimental Medicine, U.S.S.R. Academy of Medical Sciences, 197022 Leningrad 22, U.S.S.R. Search for other works by this author on: Oxford Academic PubMed Google Scholar S. A. Neifakh S. A. Neifakh 2Laboratory of Biochemical Genetics, Institute of Experimental Medicine, U.S.S.R. Academy of Medical Sciences, 197022 Leningrad 22, U.S.S.R. 4We thank Mrs. G. V. Mukha and Mrs. T. D. Aleynikova for excellent technical assistance. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 61, Issue 1, July 1978, Pages 27–34, https://doi.org/10.1093/jnci/61.1.27 Published: 01 July 1978 Article history Received: 02 August 1976 Revision received: 28 November 1977 Accepted: 12 December 1977 Published: 01 July 1978
Mucins MUC5B and MUC5AC in Distal Airways and Honeycomb Spaces: Comparison among Idiopathic Pulmonary Fibrosis/Usual Interstitial Pneumonia, Fibrotic Nonspecific Interstitial Pneumonitis, and Control Lungs
Authors: Caterina Conti, Angeles Montero-Fernandez, Elaine Borg, Tina Osadolor, Patrizia Viola, Angelo De Lauretis, Carmel J. Stock, Martina Bonifazi, Matteo Bonini, Gaetano Caramori, Gisela Lindahl, Francesco B. Blasi, Andrew G. Nicholson, Athol U. Wells, Piersante Sestini, Elisabetta Renzoni
Journal: American Journal of Respiratory and Critical Care Medicine (2016)
Vascular endothelial growth factor A &amp; D and flt1/flk1/flt4 receptor expression in metastatic lesions from prostate cancer
Authors: M. Kohli, V. Kaushal, C.-Y. Fan
Journal: Journal of Clinical Oncology (2005)

4723 Background: Early evidence suggests expression of multiple members of the vascular endothelial growth factor (VEGF) family in prostate cancer. We have recently reported gene/protein expression patterns of VEGF A,D with their cognate receptors (flk1/flt4) in primary prostatic tissue of advanced stage patients undergoing androgen deprivation1. The current study is performed to detect VEGF A,D and receptors flt1/flk1/flt4 (VEGF R1,2,3 respectively) protein expression patterns to different metastatic sites (skeletal /lymph node/soft tissue) from prostate cancer and to correlate with VEGF axis expression patterns observed in prostatic tissue in our previous study. Methods: 18 metastatic lesions from prostate cancer (6 bone/7 nodal/5 soft tissue) in 16 patients were evaluated for expression patterns by immuno-histochemistry. Intensity of staining was graded as mild (+), moderate (++) or high (+++). Results: Two specimens could not be evaluated due to inadequate tissue. VEGF D expression was detected at moderate intensity in 3 while VEGF A was observed in mild to moderate intensity in 9 specimens. Flk1 (VEGFR2) and flt4 (VEGFR3) were detected in moderate to high intensity in 14 and 15 specimens respectively while Flt1 was present focally in 4 specimens. Table illustrates expression patterns based on the location of the metastatic sites. Conclusions: Expression of multiple VEGF members in metastatic sites from primary prostate tumor appears to parallel patterns observed in freshly resected prostatic tissue of advanced stage patients undergoing transurethral prostate resection1 . The demonstration of flk1/flt4 expression in metastatic lesions with multiple VEGF ligands (A & D) is a novel observation. These findings have implications for therapeutic targeting of angiogenic/lymphangiogenic pathways in advanced prostate cancer and need further study. 1: Kaushal V, Kohli M et al: Clinical Cancer Research Jan. 2005: In press. No significant financial relationships to disclose.
Trade pact disappoints biotechnology companies and campaigners for better access to drugs
Authors: Michael McCarthy
Journal: BMJ (2015)

Industry groups representing US pharmaceutical and biotechnology companies said on Monday 5 October that provisions in the new Trans-Pacific Partnership that limit data exclusivity protections for new biologics to 5-8 years instead of the 12 years sought by the industry will discourage investment and impede development of new treatments.

In the United States, manufacturers of biologics are granted a 12 year data exclusivity period for new products, and the industry had pressed US trade negotiators to secure similar protections in the new 12 nation trade agreement.

In a statement John Castellani, president and chief executive officer of the Pharmaceutical Research and Manufacturers of America, said that a 12 year exclusivity period provided the appropriate balance between the need to create incentives for research and development investment and the need to provide access to new treatments. “While we await the final details, it appears that the ministers missed the opportunity to encourage innovation that will lead to more important lifesaving medicines …