tbuckley/cabot-search huggingface dataset:
Scatter factor/hepatocyte growth factor as a prognostic indicator in metastatic prostate cancer: A plasma study in CALGB 9480
Authors: P. Humphrey, S. Halabi, J. Picus, N. Vogelzang, E. Small, P. Kantoff
Journal: Journal of Clinical Oncology (2004)

9613 Background: Scatter factor, also known as hepatocyte growth factor, (SF/HGF) is a polypeptide growth factor thought to be important in prostate cancer growth and spread. We have previously shown circulating SF/HGF levels were related to stage and Gleason grade of prostate cancer. No previous study has assessed the relationship of circulating SF/HGF levels and clinical outcome of prostate cancer patients. Methods: SF/HGF levels in pretreatment plasma samples from 172 men with metastatic hormone-refractory prostate cancer (HRCaP) enrolled in CALGB 9480 were quantified by solid-phase enzyme-linked immunosorbet assay. CALGB 9480 was a phase III clinical trial of three different doses of suramin administered with a fixed dosing schedule in patients with advanced prostate cancer. The proportional hazards model was used to assess the prognostic importance of SF/HGF with adjustment for important baseline factors. Results: Median SF/HGF was 994 pg/ml, with a range of 212 to 2733 pg/ml. Plasma SF/HGF levels of greater than 1543 pg/ml were associated with a significant reduction in overall survival (p=0.0024). Patients with SF/HGF > 1543 pg/ml experienced a median survival of 8 months compared to 17 months for men with SF/HGF ≤ 1543 pg/ml. In multivariate analysis, adjusting for PSA, LDH, and performance status, only plasma alkaline phosphatase level (hazard ratio = 1.8, 95% CI = 1.3–2.6, p=0.0005) and elevated SF/HGF of greater than 1543 pg/ml compared to men with SF/HGF levels ≤ 1543 pg/ml (hazard ratio = 1.7, 95% CI = 1.00–2.74, p=0.048) were significantly associated with overall survival. Conclusions: Higher plasma levels of SF/HGF in men with HRCaP are associated with a worse patient survival. No significant financial relationships to disclose.
Abstract 627: Immunogenic cell death as novel immune response mechanism to EGFR-targeted therapy in CRC
Authors: Giuseppe Penna, Chiara Pozzi, Elena Magni, Giuseppe Curigliano, Maria Giulia Zampino, Maria Rescigno
Journal: Cancer Research (2014)

Abstract Colorectal cancer (CRC) is the third most common cancer worldwide. The major improvement in the median overall survival of mCRC patients was mainly due to the introduction of new active chemotherapeutic and biomolecular targeting agents. Most chemotherapeutic agents and radiotherapy kill tumor cells through an apoptotic pathway, which is considered as a non-immunogenic. However, anthracyclines, oxaliplatin or ionizing irradiation are able to induce a potent immune response in vivo, when injected in immunocompetent mice. Dying cells are readily taken up by dendritic cells (DC) that then cross-present their associated antigens for effective T cell activation. Herein we propose that the treatment with an anti-EGFR antibody (Cetuximab) in combination with chemotherapy FOLFIRI (5-fluorouracile, leucovorin, irinotecan) induces a immunogenic cell death (ICD) modality, which contributes to its clinical efficacy in patients with mCRC expressing EGFR and the wild type (wt) form of the viral oncogene v-Ki ras2. Our results, obtained on CRC cell lines provide evidence, for the first time, that treatment with Cetuximab alone or in combination with a chemotherapeutic regimen (FOLFIRI) directs dying cells towards an ICD process characterized by phosphorylation of eIF2α and, most important, increased phagocytosis by DCs. However, not all cell lines wt for KRAS (expressing EGFR) displayed the same response. As expected, Cetuximab blocked the pathways leading to AKT and ERK phosphorylation. However, we also observed that Cetuximab, and to a lesser extent the F(ab)2 fragments of Cetuximab, was inducing some phosphorylation of the EGFR in KRAS wt responding cell line, which was lower than that induced by EGF . Hence Cetuximab is uncoupling the activation of the signaling pathway induced via EGFR from EGFR phosphorylation, suggesting an alternative activation of the receptor. This allowed us to postulate that Cetuximab-induced phagocytosis may be the effect of an alternative activation of the EGFR. Indeed, we could not detect any phagocytosis in cell lines where the phosphorylation of the receptor did not occur in response to Cetuximab. These results identify ICD as novel immune response mechanism to EGFR targeted therapy alone or in combination with chemotherapy and possibly genetic alterations of the EGFR-signalling pathway, could interfere with the induction of ICD. Citation Format: Giuseppe Penna, Chiara Pozzi, Elena Magni, Giuseppe Curigliano, Maria Giulia Zampino, Maria Rescigno. Immunogenic cell death as novel immune response mechanism to EGFR-targeted therapy in CRC. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 627. doi:10.1158/1538-7445.AM2014-627
Analysis of prognostic factors in superficial urinary bladder carcinoma in our set up-a study in Jammu, J&amp;K, India
Authors: S. Sharma, A. K. Gupta, L. Gupta, J. Suri
Journal: Journal of Clinical Oncology (2004)

4713 Objective: Urinary bladder carcinoma is one of the most common malignancies. The disease incidence is on a constant rise in our area because of the better patient awareness, awareness amongst the physicians and the timely referral of the patients to the institutes where these are treated. We have analyzed the various prognostic factors that could be used to predict the outcome of the management of the superficial bladder carcinoma. Patients and Methods: 123 patients who underwent transurethral resection for superficial bladder tumors were evaluated for the analysis of the prognostic factors like tumor type, size, stage, grade multicentricity, architecture of the infiltration (papillary or solid), recurrence in first three months and associated CIS were the parameters taken for the consideration. Results: 76% patients had papillary type of the tumor and 24% had nodular type. Most of the patients with the papillary type had superficial recurrence and the nodular type had the invasive one. Tumors confined to the mucosa had recurrence in 3% of the cases.27% with the lamina propria involvement progressed to the invasive disease. Low-grade papillary tumors confined to the mucosa appear to have a low risk of recurrence and almost no risk of progression. Stage T1 tumors had high grade and increased risk of progression. Tumors with <1 cm, 1–2 cm and 2–5 cm had a recurrence rate of 22.2%, 29.4% and 31.2%26% of the patients had grade1 disease, 34% grade 11 and 40% grade 111 .43% of the patients showed recurrence during the first three months follow up check cystoscopy. Conclusion: Superficial urinary bladder carcinoma treated largely depends upon the multiple factors. Tumors with papillary type, low stage, low grade, no recurrence in the first three months, small size tumors and favorable differentiation pathologically are responsible for the excellent outcome with less chances of the progression of the disease. No significant financial relationships to disclose.
Abstract 14531: Chitinase Inhibitor, Allosamidin, Accelerates Atherosclerotic Lesions in Hyperlipidemic Mice by Influencing M1/M2 Polarization and Cholesterol Metabolism in Macrophages
Authors: Shiro Kitamoto, Kensuke Egashira, Toshihiro Ichiki, Xinbing Han, Shohei Sakuda, Kenji Sunagawa, William A Boisvert
Journal: Circulation (2012)

Objective: Chitotriosidase (Chitinase 1, CHIT1) is a glycosyl hydrolase with chitinase activity that cleaves chitin, a biopolymer ubiquitously found in insects, fungi, crustaceans, and parasites. D...
Gastrointestinal stromal tumor (GIST) that showed double new malignancies during imatinib therapy: A case report
Authors: M. Tokuhara, Y. Gouda, Y. Saito, T. Shimzu, S. Minowada, K. Sasajima, Y. Takeda, L. B. Thao, H. A. Vu, Y. Sato
Journal: Journal of Clinical Oncology (2008)

21517 Background: Imatinib therapy has remarkably improved prognosis of patients with metastatic GISTs. Thanks to longer survival of patients, secondary malignancies in association with GIST during imatinib therapy have been rarely observed, which might become another clinical problem. Methods: We report a gastric GIST case that showed a renal cell carcinoma (6 months after imatinib therapy) and a gastric carcinoma (3 years after imatinib therapy) nevertheless recurrent GIST was completely responded to imatinib. Results: A 64-year-old Japanese female was diagnosed as having a gastric GIST. Partial gastrectomy was performed with complete resection (R0). Gene mutational analysis revealed deletion of nt 1670–1684 with mutation of Lys550Ile in KIT exon 11. A year later, since she presented a recurrent peritoneal tumor, imatinib was initiated. This recurrent tumor completely responded to imatinib and has been controlled well still now. Six months after imatinib therapy was initiated, a small tumor was found in left kidney and gradually increased in size. Two and a half years after imatinib therapy, she underwent partial nephrectomy. The tumor was diagnosed as papillary renal cell carcinoma. Three years after imatinib therapy, early gastric carcinoma was found in residual stomach which was resected endoscopically. Now, she is treated with imatinib with no abnormal finding on CT scan. Conclusions: Double new malignancies during imatinib therapy have been rarely reported in the literature. No significant financial relationships to disclose.
Relationship Between Xenotransplantability and Cell Surface Properties of Ascites Sublines of a Rat Mammary Adenocarcinoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN4"&gt;4&lt;/xref&gt;
Authors: Susan C. Howard, Steven R. Hull, John W. Huggins, Coralie A. Carothers Carraway, Kermit L. Carraway
 8
Journal: JNCI Journal of the National Cancer Institute (1982)

Cell surface properties of several ascites sublines of the 13762 rat mammary adenocarcinoma were compared in an effort to understand factors important to the xenotransplantability of these tumors into C57BL/6J mice. MAT-C, MAT-C1, and MAT-cMR6-S ascites sublines were xenotransplantable; MAT-B1, MAT-C2, and MAT-MR2-S were not. All of these sublines contained a large mucin-type sialoglycoprotein (ASGP-1) as a major cell surface component. Mat-B1 and MAT-cMR6-S ASGP-1 molecules were sulfated, but MAT-C1 and MAT-MR2-S incorporated little sulfate. The major oligosaccharide of MAT-C1 ASGP-1, a disialo-oligosaccharide, was present in very low amounts in the other sublines. ASGP-1 was detected readily in the plasma of animals with MAT-C1 or MAT-MR2-S tumors, but it was not detected readily in animals with MAT-B1 or MAT-cMR6-S tumors. Thus none of these significant features of ASGP-1 that differed among the sublines correlated with xenotransplantation. However, both MAT-C1 and MAT-cMR6-S sublines had branched cell surface microvilli. Moreover, MAT-C grown in mice after xenotransplantation had extensive, branched microvilli, even though only about 10% of the population of the cells grown in the rat had them. These results suggest that the branched microvilli may provide a protective mechanism, possibly by acting as a barrier to the approach of cytotoxic cells.
A phase I trial and pharmacokinetic (PK) study of vorinostat (SAHA) in combination with 13 cis-retinoic acid (13cRA) in children with refractory neuroblastomas, medulloblastomas, primitive neuroectodermal tumors (PNETs), and atypical teratoid rhabdoid tumor
Authors: M. Fouladi, J. R. Park, J. Sun, A. M. Ingle, M. M. Ames, C. F. Stewart, R. Gilbertson, J. A. Zwiebel, P. C. Adamson, S. M. Blaney
Journal: Journal of Clinical Oncology (2008)

10012 Background: Synergistic anti-tumor activity between histone deacetylase inhibitors and retinoids has been observed in a variety of preclinical models, including pediatric CNS and solid tumors. A pediatric phase I trial of SAHA in combination with 13cRA was performed to define the dose limiting toxicities (DLT), determine the MTD, describe the PK of SAHA in combination with 13cRA, and assess accumulation of histone acetylation in peripheral blood mononuclear cells (PBMCs). Methods: 13cRA, 80 mg/m2/dose po bid, was administered on days 1–14 of each 28 day course. Oral SAHA was administered at a starting dose of 180 mg/m2/d once daily with planned escalation to the pediatric single agent MTD of 230 mg/m2/d, or dose de-escalation to 180 mg/m2/d 4 days/wk if daily dosing proved intolerable. PK analysis was performed during the first course. Acetyl-histone (H3) accumulation in vivo was studied by western blot analysis on day 1 at 0, 1, 6 and 24 h after SAHA dosing. Results: 13 eligible patients, 7 males, median age 9 years (range, 2–20) with medulloblastoma (n=4), PNET (n=6), ATRT (n=1) and neuroblastoma (n=2) were enrolled. 4/13 pts were not fully evaluable for toxicity; 2 patients continue on their first course of therapy; 1 patient had PD prior to start of therapy and 1 patient developed unrelated myelosuppression after 1 dose of SAHA. DLT occurred in 2/6 patients at the initial dose level (thrombocytopenia [n=2], neutropenia, hypophosphatemia and anorexia). 0/3 evaluable patients have experienced a DLT at 180 mg/m2/d dosed 4 times per week. Non-dose limiting grade 3 or 4 toxicities included elevated ALT (n=1), leucopenia (n=2), and lymphopenia (n=3). Western blot analysis of PBMC-derived protein isolates demonstrated accumulation of acetylated H3 histones. Conclusion: SAHA 180 mg/m2/d 4 × per week, in combination with daily 13cRA (days 1–14) appears to be well-tolerated in children and inhibits histone deacetylase activity in PBMCs. No significant financial relationships to disclose.
Influence of Age at Exposure on the Pathogenesis of Marek's Disease 2
Authors: B.W. Calnek
Journal: JNCI Journal of the National Cancer Institute (1973)

In 7 experiments, 1-day- to 4 ½-month-old chickens, free of Marek's disease virus (MDV) and MDV antibody, were exposed to clone-purified virus. Cellular preparations of the GA or JM isolate of MDV were inoculated intra-abdominally, or birds were exposed to G A virus by indirect contact. Genetically susceptible P-line birds were compared to those of the genetically resistant N-line and relatively resistant PDRC strain. Response to infection in various experiments was assessed by: incidence of MD through 56 or 70 days; infectivity of buff y coat, spleen, and kidney cells; presence of viral antigen (fluorescent antibody test) in bursa of Fabricius, spleen, and thymus; and development of precipitin and virus-neutralizing (VN) antibody. Age resistance was characterized by a) lower incidence of MD, b) reduced rate and level of infection 7–10 days post inoculation, and c) development of VN antibody. A strong age resistance developed consistently in the N-line and PDRC birds but was weak or absent in the P-line. Resistance was acquired gradually during several weeks and paralleled the acquisition of competence to make precipitin or VN antibody. During the first 3–6 days after inoculation, infection of lymphoid organs was marked and proceeded equally in all groups, regardless of age or genetic strain. However, by 10–12 days post infection, the level of infection subsided in resistant birds but not in those susceptible.
Expression of the multidrug resistance, MDR1, gene in neuroblastomas.
Authors: L J Goldstein, A T Fojo, K Ueda, W Crist, A Green, G Brodeur, I Pastan, M M Gottesman
Journal: Journal of Clinical Oncology (1990)

Metastatic neuroblastoma is a childhood malignancy that is frequently responsive to chemotherapy with doxorubicin, vincristine, and teniposide (VM26), among other drugs, but in the majority of treated patients, the tumor recurs during or after chemotherapy. In this work, we have examined the hypothesis that the development of resistance to chemotherapy in neuroblastoma might be related to the expression of the human MDR1 gene, which encodes a multidrug transporter that functions as an energy-dependent drug efflux pump. RNA samples from 49 neuroblastomas were analyzed, including 31 from untreated and 18 from treated patients. MDR1 RNA was detectable in the majority of treated and untreated tumors using a sensitive, semiquantitative slot blot assay. Of the samples from treated patients, five of 18 were found to have high MDR1 RNA levels, whereas only three of 31 from untreated patients had high MDR1 levels, a statistically significant difference (P less than .01). These results show that high levels of MDR1 RNA are often associated with resistance to chemotherapy in neuroblastoma and suggest that they may contribute to this resistance. Many of the neuroblastoma samples were also evaluated for N-myc amplification but there was no correlation between N-myc copy number and the level of MDR1 mRNA expression.
Phase II study of first-line sagopilone combined with prednisone in patients with metastatic castration-resistant prostate cancer (CRPC)
Authors: T. M. Beer, D. C. Smith, A. Hussain, M. Alonso, J. Wang, M. Giurescu, Y. Wang
Journal: Journal of Clinical Oncology (2009)

5059 Background: Epothilones comprise a new class of microtubule stabilizing agents, and sagopilone is a novel, fully synthetic epothilone that has shown significant activity against a broad range of tumor models. Methods: Chemotherapy-naïve metastatic CRPC patients received sagopilone 16 mg/m 2 IV over 3 hours every 21 days and prednisone 5 mg PO BID. The primary efficacy evaluation was based on PSA decline (≥50% PSA reduction confirmed at least 28 days apart). The Simon 2-Stage design required 3 responders among the first 13 evaluable patients and 13 responders among the first 46 evaluable patients to declare the agent of interest for further investigation. Results: Between August 2006 and May 2008, 53 patients were enrolled and treated. Sites of metastases were: bones, lymph nodes, and viscera in 72%, 68%, and 25% patients, respectively. Median PSA was 107.5 (6.2–1727) ng/ml. A median of 5 (2–12) cycles were delivered. The median dose delivered per cycle was 13.3 mg/m 2 . Two patients did not meet all eligibility criteria and were excluded from efficacy analyses; 3 additional patients were excluded from PSA decline and progression-free survival analyses due to missing baseline PSA assessment. Twenty of 48 patients (42%; 80% CI: 32%-52%) had a confirmed PSA decline in excess of 50% and 30 (63%; 95% CI: 47%-76%) had a 30% reduction in PSA within 3 months of enrollment. Of 39 patients with measurable disease by RECIST, 1 had a complete, 9 had a partial confirmed response (26%; 95% CI: 13%-42%). The median PFS was 6.4 months (95% CI: 4.7 to 10.2). All 53 patients are evaluable for safety. Toxicities occurring in ≥ 20% patients included peripheral neuropathy 74% (19% grade 3), fatigue 40% (6% grade 3, 2% grade 4), extremity pain 36% (6% grade 3), arthralgia 23% (no grade 3, 4), and constipation 21% (no grade 3, 4). Conclusions: Sagopilone is active in metastatic chemotherapy-naïve CRPC patients, with probability of PSA decline, measurable disease responses, and PFS approximating the current standard of docetaxel + prednisone. Neuropathy and fatigue are the most common toxicities, while hematologic toxicity is rare. Further evaluation of this agent in prostate cancer is warranted. [Table: see text]
ABT-869 in non-small cell lung cancer (NSCLC): Interim results
Authors: E. Tan, R. Salgia, B. Besse, G. Goss, D. R. Gandara, N. Hanna, J. Steinberg, J. Steinberg, J. Qian, D. M. Carlson, R. Soo
Journal: Journal of Clinical Oncology (2009)

8074 Background: ABT-869 is a novel orally active, potent and specific inhibitor of vascular endothelial growth factor and platelet derived growth factor receptor tyrosine kinases. Methods: This ongoing, open-label, randomized, multicenter phase 2 trial of ABT-869 at 0.10 mg/kg daily (Arm A) and 0.25 mg/kg daily (Arm B) until progressive disease (PD) or intolerable toxicity, was initiated to assess antitumor activity and toxicity of ABT-869 in patients (pts) with NSCLC. Eligibility criteria included locally advanced or metastatic NSCLC; ≥ 1 prior systemic treatment, and ≥1 measurable lesion by RECIST criteria. The primary endpoint was the progression free (PF) rate at 16 wks. Secondary endpoints were objective response rate (ORR), time to progression (TTP), progression free survival (PFS) and overall survival (OS). CT scans were assessed by the investigator and centrally; central assessment results are provided. Results: 138 patients (pts) were enrolled from 08/07–10/08 from 27 centers with interim data available for 94 pts (Arm A, n=43; Arm B; n=51). Median age was 64 years and 62 years in Arm A and B respectively. For the interim analysis population (Arm A, n=24; Arm B, n=24), 16 (33.3%) pts were PF at 16 wks: 7 (29.2%) in Arm A and 9 (37.5%) in Arm B. The ORR in Arm A (n=30) was 0% and 7.3% in Arm B (n=41). The median TTP and median PFS were 110 and 109 days, and 112 days and 108 days in Arm A and B, respectively. The most common adverse events (AEs) in Arm A were fatigue (35%), nausea (21%), and anorexia (21%), and in Arm B were hypertension (51%), fatigue (51%), diarrhea (43%), anorexia (41%), nausea (31%), proteinuria (31%) and vomiting (26%). The most common grade 3/4 toxicities in the Arm A were fatigue (7%), ascites (5%), dehydration (5%), pleural effusion (5%), and in the Arm B were hypertension (23%), fatigue (8%), PPE syndrome (8%), dyspnoea (6%) and stomatitis (6%). Most AE's were mild/moderate and reversible with interruptions/dose reduction/or discontinuation of ABT-869. Conclusions: ABT-869 demonstrates an acceptable safety profile and appears to be active in NSCLC patients. [Table: see text]
Oncological Characteristics of Radiological Invasive Adenocarcinoma with Additional Ground-Glass Nodules on Initial Thin-Section Computed Tomography: Comparison with Solitary Invasive Adenocarcinoma
Authors: Aritoshi Hattori, Takeshi Matsunaga, Kazuya Takamochi, Shiaki Oh, Kenji Suzuki
Journal: Journal of Thoracic Oncology (2016)