tbuckley/cabot-search huggingface dataset:
Phase II study of SB1518, an orally available novel JAK2 inhibitor, in patients with myelofibrosis.
Authors: H. J. Deeg, O. Odenike, B. L. Scott, Z. Estrov, J. E. Cortes, D. A. Thomas, H. J. Zhu, H. Kantarjian, S. Verstovsek
Journal: Journal of Clinical Oncology (2011)

6515 Background: The JAK2V617F mutant enzyme has been linked to the pathogenesis of myeloproliferative neoplasms. SB1518 is a potent inhibitor of JAK2 and its JAK2V617F mutant. In Phase 1 study, myelofibrosis (MF) patients treated with SB1518 achieved steady-state plasma levels above the IC50 for JAK2 at all doses (100‐600 mg/d). Target inhibition, measured by phosphorylation of STAT3, STAT5, and JAK proteins in PBMCs and whole blood, was also shown at all doses. 400 mg/d was chosen for Phase 2 study based on response rate, safety, and tolerability. Methods: The primary Phase 2 objective was to evaluate spleen response rate, measured by the change in MRI-assessed spleen volume, in patients given SB1518 orally once a day in 28‐day cycles. Eligible patients had primary, post-PV, or post-ET MF, splenomegaly ≥ 5 cm below the left costal margin (LCM), and were not suitable for standard therapy. Results: 33 patients with MF were enrolled. Median spleen enlargement by physical examination (PE) was 18 cm below the LCM. Of 30 patients assessed by MRI, 29 had a spleen volume reduction; 17 (57%) had a reduction of ≥ 25%. Of 31 patients assessed by PE, 12 (39%) had a reduction of ≥ 50%, and 7 (23%) had a reduction of 100%. Results showed that a 50% reduction in spleen length by PE (i.e., the threshold specified in IWG‐MRT criteria) corresponds to a 25% reduction in spleen volume by MRI (p=0.043). Intensity of MF-related symptoms decreased by 40-65% in patients treated for 6 months. The most common treatment-related toxicities were diarrhea (81%; 6% Gr 3), nausea (41%; all Gr 1/2), vomiting (22%; all Gr 1/2), and fatigue (9%; all Gr 1/2). These events were readily managed. 8 patients reduced the dose during the first 6 months. At 6 months, 21 patients remain on therapy. Significant neutropenia and thrombocytopenia were not seen (no Gr 3/4 events). SB1518 was tolerated equally well by patients with normal platelet counts and those with thrombocytopenia. Conclusions: SB1518 shows promising efficacy in symptomatic MF patients with splenomegaly. Once daily dosing is well tolerated, with manageable GI toxicity as the main side effect. Patients with significantly impaired hematopoiesis can receive full-dose daily SB1518 without exacerbating hematocytopenias.
Mature data on capecitabine (X) + fractionated cisplatin (P) as first-line therapy in patients (pts) with advanced gastric carcinoma (AGC)
Authors: M. Jin, L. Shen, B. Hu, J. Yu, Z. Wen, Y. Su, B. Wang, L. Chen, H. Ying, L. Chen
Journal: Journal of Clinical Oncology (2006)

4075 Background: Gastric cancer is one of the most common malignancies in Asia with an adjusted mortality rate above 20/100,000 population. 5-FU + fractionated P is a standard treatment for AGC in China. In a Korean study by Kim et al., X + P produced a response rate of 55% in pts with previously untreated AGC. Here we present mature efficacy/safety results in Chinese pts with AGC. Methods: 154 pts of a planned population of 120 pts were enrolled between Jun 2002 and Aug 2004. All had measurable AGC (WHO), Karnofsky performance status ≥60, adequate bone marrow, renal and hepatic functions. Prior radiotherapy or adjuvant chemotherapy was permitted. Pts received × 1000 mg/m 2 orally bid on days 1–14 + P 20mg/m 2 /day i.v. on days 1–5, every 3 weeks for 6 cycles. The primary endpoint was time to disease progression (TTP). Results: Baseline characteristics of the 141 evaluable pts (104 men, 37 women) are: median age 54 years (range 23–80), main sites of metastases: lymph nodes 45%, liver 40%, stomach 18%, skin 6%, other 6%, lung 5%, abdomen 4%. The overall response rate was 36%, including 13 complete responses and 38 partial responses. After a median follow-up period of 12 months, the median TTP is 9 months (95% CI, 9–12 months) and the median overall survival is 12 months (95% CI, 12–15 months). Median treatment duration was 6 cycles (range 3–6). The most common treatment-related clinical adverse events (all grades &gt;5%) were: hand-foot syndrome (HFS) 25%, leucopenia 13%, and SGOT abnormality 12%. The most commongrade 3 adverse events were SGPT abnormality 3%, HFS 2%, and anemia 2%. There were no grade 4 adverse events. Most grade 3 adverse events improved or resolved after treatment or interruption except in 1 pt with anemia who withdrew after 2 cycles. Conclusions: X combined with fractionated P is highly active and very well tolerated as first-line treatment for AGC, with comparable results to 5-FU + P. No significant financial relationships to disclose.
Feline Leukemia After Feline Infectious Anemia 2
Authors: William A. Priester, Howard M. Hayes
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Feline Leukemia After Feline Infectious Anemia Get access William A. Priester, William A. Priester Epidemiology Branch, National Cancer Institute,4Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Howard M. Hayes Howard M. Hayes Epidemiology Branch, National Cancer Institute,4Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 1, July 1973, Pages 289–291, https://doi.org/10.1093/jnci/51.1.289 Published: 01 July 1973 Article history Received: 15 January 1973 Accepted: 18 April 1973 Published: 01 July 1973
Outcomes of concurrent chemo-radiotherapy (CCRT) in locally advanced cervical cancer (LACC). Results of a retrospective analysis of a single institution
Authors: J. J. Zarba, P. Gonzalez Jazey, R. Pedruzzi, L. de Gregorio, J. G. Chavanne, E. Muela, R. Audi, S. Forneris, P. Gonzalez
Journal: Journal of Clinical Oncology (2005)

5165 Background: CCRT is considered the standard of care in LACC since 1999. However there are few reports of results of this treatment in the common practice in developing countries were this disease is most frequent. Material and Methods: The records of all patients (pts) with LACC treated in our service between 1998 and 2002 were reviewed. Overall survival (OS) and Disease Free Survival (DFS) were the main outcomes of our review. Results: The records of 284 pts with LACC treated in our institution were reviewed. 142 pts were treated with CCRT from 1998 to 2002. The pts characteristics were: Stage: (%) IB 2 (1.4), IIA 3 (2.1), IIB 60 (42.2), IIIA 3 (2.1), IIIB 69 (48.5), IVA 2 (1.4). The median age was: 47 (21–79) The histology was squomous in all pts. The chemotherapy regimen (C) used were: between 1998 and 1999: Ifosfamide (I), Cisplatin (P) +/- Bleomicine (B), (BIP/IP) in 27 pts (19) and since 1999: weekly P (40 mg/m2) in 94 pts. (66) and weekly P/Gemcitabine (G) in 21 pts (15) All pts had a planed external beam radiation therapy with a cobalt unit (5040 cGy in 5.6 weeks) and a single application of brachytherapy (30–35 Gy on point A).122 pts (85) had a complete radiation as planed. There were one death related to treatment with BIP CT and there were no toxic deaths with the others regimens, 5 pts (3.5) abandon treatment, all with weekly P. The median follow up was: 24 months (m) (1–83). 44 pts were early lost in follow up (less than 10 months. The overall survival was 83%. with a DFS 59% (84/142). 13 pts (9) progressed and 39 pts (27) recurred, the median TTP was 15 m (4–40). The DFS by stages was: IIB 65%, IIIB/IVA 56% and by C regimen was: BIP/IP 55%, P/G 76% and P 56%. The median follow up for BIP/IP 35 m, P/G 33 m and P 19 m. Conclusions: CCRT is feasible in a community hospital of a developing country. However, the DFS seems to be below to that reported in randomized trials, especially for weekly cisplatin and radiation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly
Abstract 12241: Pharmacological Inhibition of PAI-1 Rescues the Defect in Ischemia-Induced Neovasculature in Type II Diabetic Mice
Authors: Rong Li, Xiao Zhang, Meiping Ren, Mao Luo, Kai Yan, Tammy L Strawn, William P Fay, Jianbo Wu
Journal: Circulation (2013)

Background: Type II diabetes mellitus (DM) leads to the development of microvascular diseases and is associated with impaired angiogenesis. Elevated plasma levels of plasminogen activator inhibitor...
Further Cytologic and Histologic Studies of Bladder Lesions in Workers Exposed to Para-Aminodiphenyl: Progress Report
Authors: Leopold G. Koss, M.D., Myron R. Melamed, M.D., R. Emmet Kelly, M.D.
Journal: JNCI Journal of the National Cancer Institute (1969)

This is the third interval report on a long-term study of 503 men accidentally exposed to a potent bladder carcinogen, para-amino-diphenyl (xenylamine). To date, 35 men developed histologically proved carcinoma of the bladder. Cytologic studies of urinary sediment suggested that, after exposure, three distinct periods may be observed in the course of the disease: 1) a period of cytologic and clinical negativity, lasting several years; 2) a period of cytologic abnormalities in the absence of clinical disease; 3) a period of cytologic and clinical carcinoma. Histologic studies of bladder biopsies obtained during the second period disclosed that nonpapillary carcinoma in situ is usually the source of abnormal cells. Follow-up studies on a group of 13 men with nonpapillary carcinoma in situ ab initio are reported. To date, invasive carcinoma of the bladder developed in 7 of these men. In 4, the urinary sediment still shows cytologic abnormalities suggestive of cancer, but there is no clinical evidence of cancer as yet. In 2 men, the smears became normal after biopsies of the lesion. This follow-up continues. In some exposées, suspicious cytologic abnormalities disappeared spontaneously, reverting to normal cytologic pattern, often after several years of follow-up. Thus, some of the lesser epithelial lesions may apparently spontaneously revert to normal. There is no obvious difference between the clinical course of carcinomas of the bladder, whether they have followed exposure to p-aminodiphenyl or have occurred spontaneously. However, nonpapillary carcinoma in situ of the bladder is apparently a much more aggressive lesion than carcinoma in situ of the uterine cervix.
Bevacizumab plus low-dose metronomic oral cyclophosphamide in heavily pretreated recurrent ovarian cancer.
Authors: A. Sánchez-Muñoz, C. Mendiola, C. A. Rodriguez, E. Pérez-Ruiz, J. M. Jurado, L. Alonso-Carrión, I. Ghanem, G. Deelasco, C. Quero Blanco, E. Alba
Journal: Journal of Clinical Oncology (2010)

e15507 Background: To assess the efficacy and safety of bevacizumab plus low-dose metronomic oral cyclophosphamide in heavily pretreated patients with recurrent ovarian cancer. Methods: Patients with recurrent ovarian cancer and prior treatment with a platinum and taxane based chemotherapy were included. Treatment consisted of bevacizumab 10 mg/kg intravenously every two weeks plus oral cyclophosphamide 50 mg daily until disease progression or unacceptable toxicity. Response rates were determined according RECIST criteria and by monitoring the CA125 serum tumor marker according to Rustin' criteria. The endpoints were progression free disease (PFS), response rate (RR), overall survival (OS) and safety. Results: Thirty eight patients were treated, 79% were platinum resistant and 21% platinum sensitive. 79% of patients had received more than two previous lines of treatment. 81% of patients had received gemcitabine, 76% liposomal doxorubicin and 50 % topotecan. A median of 8 (r: 1-70) cycles of bevacizumab were administered. The overall response rate was a complete response (CR) in 3 patients (8.1%), a partial response (PR) in 12 (32.4%) and a stable disease ≥ 6 months (SD) in 3 (8.1%). Median PFS and overall survival were 4.5 and 10.7 months, respectively. 16 patients (42%) were progression free for at least 6 months. There was a significant relation of prior platinum response and performance status with the hazard of progression. Grade 3-4 toxicities included anemia (1), hypertension (2), hematuria (1), arterial thrombosis in the leg (1), dysnea (1) and intestinal fistulae (1). There were no cases of gastrointestinal perforation. Conclusions: The combination of bevacizumab and metronomic cyclophospamide was active and well tolerated for heavily pretreated recurrent ovarian cancer patients. No significant financial relationships to disclose.
Source of Increased Ferritin in Neuroblastoma: Studies With Concanavalin A-Sepharose Binding&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: H W Hann, M W Stahlhut, A E Evans
Journal: JNCI Journal of the National Cancer Institute (1986)

Serum ferritin is present in two forms--a glycosylated form that results from active secretion by cells and a nonglycosylated form that is directly released by damaged cells. Glycosylated ferritin binds to concanavalin A (Con A) through the glucose and/or mannose residues of the molecule. Patients with neuroblastoma frequently present at diagnosis with abnormally elevated levels of serum ferritin. The ferritin levels will, however, return to normal with clinical remission, suggesting that the tumor is the origin of the elevated ferritin. With the use of a Con A binding assay, an investigation was made as to whether the increased levels of serum ferritin at diagnosis in neuroblastoma patients resulted from active secretion by the tumor or were the consequence of direct release of ferritin from damaged tissue. Serum samples were collected at diagnosis from 36 children with neuroblastoma and from 16 normal healthy subjects. Tissue ferritins were purified from normal human liver, placenta, HeLa cells, human neuroblastoma, and hepatoma cells grown in culture. Serum and tissue ferritins were measured before and after binding with Con A. Sixty-three percent of serum ferritin from neuroblastoma patients and 66% of serum ferritin from normal subjects were bound to Con A, suggesting that they were glycosylated and were likely to have been secreted. On the other hand, only 28% of tissue ferritin were bound to Con A. Furthermore, most patients showed abnormally elevated levels of serum ferritin, and 63% of these ferritins were bound to Con A. These results are compatible with the hypothesis that much of the elevated ferritin in sera of patients with neuroblastoma seen at diagnosis is the result of secretion of ferritin by the tumor.
Prognostic system for hepatitis B virus (HBV)-related hepatocellular carcinoma- Prospective validation of the Chinese University Prognostic Index
Authors: W. Yeo, T. G. Liem, S. L. Chan, P. E. Hui, K. C. Lam, B. B. Ma, J. Koh, T. S. Mok, T. W. Leung, A. T. Chan, F. K. Mo
Journal: Journal of Clinical Oncology (2008)

4591 Background: Prognosis of patients with HBV-related chronic liver disease and hepatocellular carcinoma (HCC) depends on both extent of tumor involvement and functional hepatic reserve. The Chinese University Prognostic Index (CUPI) includes the following factors-TNM staging system, total bilirubin, ascites, alkaline phosphatase, α-fetoprotein, and asymptomatic disease on presentation; these factors carried different weights that have been derived from the regression analysis to construct the CUPI. Methods: In this prospective study, 726 HCC patients were scored with CUPI at disease presentation, the discriminatory ability and predictive power of CUPI was compared with that of the TNM and Okuda staging systems and CLIP prognostic score. All patients were followed up for survival. Results: 84% were males; the median age was 58 years. The majority of patients had HBV-related HCC (81%). The median follow-up period was 32.5 months (95% CI 29.2–36.3). The TNM and Okuda staging systems, as well as CLIP prognostic score had prognostic significance. However, the CUPI enables characterization of three risk groups with highly significant differences in survival during the whole period of follow-up (p <0.0001). CUPI was more discriminant than the other systems in differentiating poor prognostic patients (high risk group) from the other patients (low and intermediate risk groups) in terms of a greater survival predictive power. Conclusions: In the study population of patients with mainly hepatitis B-associated HCC, the CUPI was more discriminant than the TNM and Okuda staging systems, or the CLIP prognostic score in classifying patients into different risk groups and was better at predicting survival. No significant financial relationships to disclose.
Salvage treatment for Hodgkin's disease in relapse.
Authors: D E Bergsagel
Journal: Journal of Clinical Oncology (1987)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1987.5.4.525 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3549985 Salvage treatment for Hodgkin's disease in relapse. D E BergsagelxD E BergsagelSearch for articles by this author https://doi.org/10.1200/JCO.1987.5.4.525 PDF "Salvage treatment for Hodgkin's disease in relapse.." Journal of Clinical Oncology, 5(4), pp. 525–526© 1987 by American Society of Clinical Oncology
MET 14 Deletion in Sarcomatoid Non-Small-Cell Lung Cancer Detected by Next-Generation Sequencing and Successfully Treated with a MET Inhibitor
Authors: Carrie Lee, Dimitry Usenko, Garrett M. Frampton, Caitlin McMahon, Siraj M. Ali, Jared Weiss
Journal: Journal of Thoracic Oncology (2015)
Multiple lines of chemotherapy in relation to survival of patients on recurrence with advanced ovarian cancer
Authors: G. P. Stathopoulos, S. K. Rigatos, G. Aravantinos, N. A. Malamos, J. Koutandos, J. G. Stathopoulos, S. Batzios, C. Batziou
Journal: Journal of Clinical Oncology (2008)

16553 Background: 60–70% of patients with ovarian cancer will remain with advanced disease after front line treatment. A few cytotoxic agents have been suggested for second line treatment on the basis of their effectiveness. Patients after recurrence survive for an unpredictable period of time, often of very long duration. In the present study the objectives were: response and patients survival in relation to the number of chemotherapy treatments. Methods: All patients had been treated before with chemotherapy, surgery or both. The estimation of disease evolution started on recurrence or after failure of first line treatment. All had histological or cytological confirmation of epithelial ovarian carcinoma and were of stage III (a, b, c) and IV. Front-line chemo was Cisplatin or Carboplatin combined with Paclitaxel or Cyclophosphamide. The second line included a combination based on Cisplatin or analogues, Taxane, anthracycline, Liposomal anthracycline, Topotecan. Second agents for the combination were: Gemcitabine, Vinorelbine, Cyclophosphamide, Ifosfamide, Irinotecan. Those agents were repeated in different series of combined schedules numbered from 1 to 9, with average 3 series. Treatment free Intervals varied from 1 month to 36 months, with median 7 months. CA-125 was estimated, but was not the main criterion for restarting chemotherapy. The patients were divided in three groups on the basis of the number of chemotherapy series. Results: 106 patients were reviewed and 85 of those were evaluated. The median follow-up was 5 years and range from 2 years to 10 years. The median age was 61 years (range 34–82). 2d surgery was performed in 25% of the patients (for cytoreduction) but apart of 4% of those, disease remained at stage III. Response percentage (PR) was 19%, stable disease 54% and progressive disease 14.42%. Median survival was 49 months with range 20-120 months. Group A (38 pat.) had 1–2 lines of chemotherapy. Group B (20 pat.) had 3 lines and group C (27 pat.) had 4–9 lines of chemotherapy. The overall survival of group C versus group A was not statistically significant (p=0.1442). Conclusion: No advantage in survival of patients with multiple chemotherapy treatments versus 1–2 was observed. The percentage of non responders to chemotherapy after recurrence was 80%. No significant financial relationships to disclose.
IL-6 pathway in the liver: From physiopathology to therapy
Authors: Dirk Schmidt-Arras, Stefan Rose-John
Journal: Journal of Hepatology (2016)

SummaryInterleukin 6 (IL-6) is a pleiotropic four-helix-bundle cytokine that exerts multiple functions in the body. In the liver, IL-6 is an important inducer of the acute phase response and infection defense. IL-6 is furthermore crucial for hepatocyte homeostasis and is a potent hepatocyte mitogen. It is not only implicated in liver regeneration, but also in metabolic function of the liver. However, persistent activation of the IL-6 signaling pathway is detrimental to the liver and might ultimately result in the development of liver tumors. On target cells IL-6 can bind to the signal transducing subunit gp130 either in complex with the membrane-bound or with the soluble IL-6 receptor to induce intracellular signaling. In this review we describe how these different pathways are involved in the physiology and pathophyiology of the liver. We furthermore discuss how IL-6 pathways can be selectively inhibited and therapeutically exploited for the treatment of liver pathologies.
A phase II trial of pemetrexed in patients with recurrent thymoma or thymic carcinoma
Authors: P. J. Loehrer, C. T. Yiannoutsos, S. Dropcho, M. Burns, P. Helft, E. G. Chiorean, R. P. Nelson
Journal: Journal of Clinical Oncology (2006)

7079 Background: Few prospective trials have been conducted in patients with advance thymic malignancies. Pemetrexed a multi-targeted antifolate with a broad range of clinical activity, but previously untested in thymic malignancies. As a result, a phase II trial was initiated to evaluate the clinical activity of pemetrexed in previously treated patients with thymoma (THY) and thymic carcinoma (TC). Methods: From February, 2005 to November, 2005, twenty-seven previously treated patients with unresectable stage IVA (n = 16) or stage IVB (n =11) disease were treated with pemetrexed at a dosage of 500 mg/m 2 every three weeks for a maximum of 6 cycles or until undue toxicity or progressive disease. All patients received folic acid, vitamin B12 and steroid prophylaxis. Profile of patients include: median age = 52 years (range 26–84); M: F = 13:14; PS 0/1= 17/10; median number of prior therapies = 2 (range 1–6); 21 had prior radiation therapy; and histology (THY = 16, TC = 11). Results: The median number of cycles administered was 5 (range 1–6). Eleven patients had grade 3 toxicities including: dyspnea, infections, fatigue, abnormal chemistries and neutropenia. No Grade 4 toxicities were noted. Accrual was completed in November, 2005 with four patients still on therapy. In 23 fully evaluable patients, two complete and two partial responses (RECIST) were noted. All four responding patients had had stage IVA thymoma. Five patients progressed on therapy and two patients discontinued therapy for intolerance to chemotherapy (constipation, dyspnea) and 1 patient for progressive Morvan’s Syndrome. The median time to progression for all patients was 45 weeks (THY = 45.4 weeks vs. TC = 5.1 weeks). With three deaths thus far, the median overall survival has not been reached. Conclusions: Pemetrexed is an active agent in a heavily pretreated population of patients with recurrent thymoma. Patients with recurrent thymic carcinoma appear to have a much more aggressive clinical course than thymoma. [Table: see text]