tbuckley/cabot-search huggingface dataset:
A multicenter phase II trial of bi-weekly irinotecan (CPT11), infusional 5-fluorouracil (5FU) and leucovorin (LV) with oral tegafur/uracil (UFT) for metastatic colorectal cancer (MCRC)
Authors: T. Kono, I. Tomita, S. Kasai, N. Chisato, T. Asama, K. Kamiya, Y. Yamamoto, N. Kawabata, M. Ihara
Journal: Journal of Clinical Oncology (2004)

3666 Background: : CPT11 combined with continuous infusional 5FU has shown to be an effective and tolerable regimen in MCRC.UFT enhanced plasma 5FU concentration and anti-tumor effects during 5FU infusion. We examined phase II trial of CPT11/infusional5FU/LV/UFT combined therapy for MCRC. Methods: CPT11; 30 mg/m2 (day1, i.v.1hr), leucovorin (LV); 200 mg/m2 (day1, 2i.v.1hr), 5-fluorouracil (5-FU); 300 mg/m2 (day1, 2c.i.v. in 22hr) bi-weekly, UFT was 400mg/day (day1–14 p.o.). Based on newly available phase I trial results, the CPT11 dose was reduced from 100 to 30 mg/m2 after January 2001. The main endpoint of this trial was the objective tumor response rate (RECIST criteria). Results: Sixteen patients with good performance status (ECOG0–1) entered the trial from February 2001 until May 2002 (9m/7f; median age=62, range39–77). The response rate was 19% (3PR) (RECIST criteria). Stable disease (SD) plus partial response was 100% (16/16). Median time to progression (TTP) was 5.2 months and median survival time (MST) was 20.2 months (95%CI: 14.6–25.8). In total, 416 cycles were administered, with a median of 26cylcles (MC)(range: 5–61). Presence of TTP (P=0.04 loglank) and MC (P=0.02 loglank) correlated with MST.The major toxicity was not recognized. Grade1/2 nausea was common.No treatment related death was recorded. Conclusions: Considering toxicity, TTP and economic burden of a patient, the bi-weekly CPT11/infusional5FU/LV/UFT regimen will be used for further comparative trials of the group. As for this regimen, long-term outcome treatment is possible and the quality of life analyses will be presented at the meeting. No significant financial relationships to disclose.
Chemosensitivity test using collagen gel droplet-embedded culture may predict effectiveness of adjuvant therapy for gastric cancer
Authors: T. Nishida, M. Yoshikawa, T. Kitagawa, T. Ito, H. Matsuda
Journal: Journal of Clinical Oncology (2004)

4218 Background: The prediction of effectiveness of chemotherapy is important for patients' QOL and cost-effectiveness. We conducted prospective multicenter study to evaluate chemosensitivity test using the collagen gel droplet-embedded culture (CD) system for 5FU-based adjuvant chemotherapy for the gastric cancer. We compared three year-disease free survival according to the chemosensitivity test. Methods: Inclusion criteria are adults with stage II or III (JCGC) gastric cancer and good performance status (<2). After written IC, fresh cancer specimens were obtained and cultured in the CD system with or without agents. The tumor cell growth ratio in the presence or absence of 0.2 mg/l 5FU (T/C) was determined. Activities of DPD, TS, and TP in tumors are also measured. Following curative resection, 66 patients were registered and received the single protocol of 5FU-based adjuvant chemotherapy (two weeks i.v. therapy of 320 mg/m2 5FU and 5 mg/m2 CDDP, and one year oral intake of 200 mg/day 5FU). Tumors are considered sensitive to agents when T/C is less than 50%. Fifty-five patients fulfilled clinicopathologic criteria and laboratory data. Among 55 patients, 28 are considered resistant and the other 27 sensitive. Results: Between the two groups, no differences in age, gender, PS, operative methods, lymph node dissection, pathological T, N, M, as well as stages, and histology, After 3 years follow-up, 20 patients of 28 in the resistant group recurred, and 9 patients of 27 in the sensitive group did (P=0.0069). Disease-free survival of the sensitive group is significantly longer than that of the resistant group (P=0.0176). There is significant difference in overall survival between two groups (31 months for sensitive 26 for resistant). No differences in DPD, TS, and TP activities between two groups. Multivariate analysis indicates that chemosensitivity test is an independent predictor of disease free survival. Conclusions: Chemosensitivity test may estimate disease-free survival of patients with stage II and III gastric cancers after adjuvant chemotherapy and may be useful to predict efficacy of adjuvant chemotherapy. No significant financial relationships to disclose.
Heat shock protein 70 potentiates interferon alpha production by plasmacytoid dendritic cells: relevance for cutaneous lupus and vitiligo pathogenesis
Authors: C. Jacquemin, J. Rambert, S. Guillet, D. Thiolat, N. Boukhedouni, M.‐S. Doutre, A.‐S. Darrigade, K. Ezzedine, P. Blanco, A. Taieb, K. Boniface, J. Seneschal
Journal: British Journal of Dermatology (2017)

Plasmacytoid dendritic cells (pDCs) are a subset of dendritic cells specialized in the production of type I interferon (IFN-α/β) and involved in various cutaneous inflammatory and autoimmune disorders, such as cutaneous lupus erythematosus (CLE) and vitiligo. Heat shock proteins (HSPs) are molecular chaperones essential for maintaining cellular functions, but they can act as a danger signal during inflammation.To decipher the role of HSP70 in the production of IFN-α by pDCs in CLE and vitiligo.Expression of HSP70 and CD123+ pDCs was analysed by immunohistochemistry or immunofluorescence in CLE and vitiligo skin samples. Flow cytometry was performed to analyse expression of HSP70 receptors, activation markers on pDCs and DNA uptake by pDCs in the presence of HSP70. The impact of HSP70 on DNA-induced IFN-α secretion by pDCs was evaluated by enzyme-linked immunosorbent assay (ELISA). The effect of IFN-α on chemokine (C-X-C motif) ligand 9 (CXCL9)/10 gene and protein expression by keratinocytes was determined by real-time polymerase chain reaction and ELISA.Infiltration of pDCs in CLE and progressive vitiligo was primarily located in the epidermis, close to keratinocytes expressing HSP70. In vitro experiments revealed that the pDCs expressing HSP70 receptor Lox-1 (lectin-like oxidized low-density lipoprotein-receptor-1) were able to aggregate HSP70. Exogenous HSP70 induced activation of pDCs and increased the uptake of exogenous DNA. Furthermore, HSP70 potentiated DNA-induced IFN-α production by pDCs. Finally, IFN-α induced expression of CXCL9 and CXCL10 by keratinocytes.These data demonstrate that interaction between HSP70 and pDCs in CLE and vitiligo is a prerequisite for the enhancement of IFN-α production, and could be an interesting target.
Aberrant TNFAIP3 Induces Mesenchymal Stem Cell Impairment Via the NF-Kb/SMAD7 Signaling Pathway in Immune Thrombocytopenia
Authors: Yun He, Jia-Min Zhang, Lin-Lin Xu, Xiao-Lu Zhu, Qian Jiang, Hao Jiang, Jin Lu, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang, Xiao-Hui Zhang
Journal: Blood (2016)
A phase I/II clinical trial of intravenous (I.V.) calcitriol with fixed doses of cisplatin and docetaxel in advanced non-small cell lung cancer.
Authors: Nithya Ramnath, Stephanie Daignault-Newton, Grace K. Dy, Josephia Muindi, Araba Adjei, Gregory Peter Kalemkerian, Kemp Bailey Cease, Philip J. Stella, Dean E. Brenner, Candace S. Johnson, Donald L. Trump
Journal: Journal of Clinical Oncology (2012)

e18118 Background: In vitro and in vivo studies have demonstrated the antiproliferative effects of 1, 25 (OH) 2 D 3 (calcitriol) as single agent and antitumor synergy with cisplatin. The goals of this Phase I/II study were to determine the maximum tolerated dose (MTD) of 1, 25 (OH) 2 D 3 in combination with cisplatin and docetaxel, and to evaluate the efficacy in patients (pts) with metastatic NSCLC.Methods: The study was a multicenter, open-label study in pts with metastatic NSCLC. Pts were adults 18 yrs., PS 0-1 with normal liver/kidney function. For the phase I study, pts (3–6 per cohort) received 1, 25 (OH) 2 D 3 I.V. every 21 days prior to docetaxel and cisplatin. The starting dose of 1,25 (OH) 2 D 3 was 15 mcg/m 2 at sequential ascending dose levels (DL) (15, 30, 60 and 80 mcg/m 2 ) using a 3+3 design targeting a dose-limiting toxicity (DLT) rate of &lt;33%. Docetaxel was administered at 75 mg/m 2 and cisplatin 75mg/m 2 following 1, 25 (OH) 2 D3 for 4 cycles. We analyzed SNPs in the CYP24A1 gene.Results: 37 pts were enrolled (16 in phase I and 21 in phase II) with a median age of 54 (range 34–79) yrs.; M: F, 12:17. At the 80 mcg/m 2 dose level, 2/4 pts had DLT of grade 4 neutropenia. There were no cases of hypercalcemia or azotemia. The MTD and recommended Phase II dose was 60 mcg/m 2 . Among 6 response-evaluable Phase I pts, and 21 phase II pts, there were: 2 confirmed partial responses (PR), 6 unconfirmed PRs and 10 pts with stable disease. The median time to progression was 6.9 months (95% CI 4.4, 12.9) and the median overall survival was 8.3 months (95% CI 5.8, 14.9). Of the CYP24A1 SNPs, the IVS4-308C&gt;G was associated with progressive disease (Chi-Square=0.0062)Conclusions: The MTD of 1,25 (OH) 2 D 3 in combination with docetaxel and cisplatin was 60 mcg/m 2 IV every 21 days. Pre-specified endpoint of a 50% response rate was not met in the phase II study. However, disease control in 66% of patients argues for further study of 1,25 (OH) 2 D 3 as maintenance therapy. The CYP24A1 polymorphism IVS4-308C&gt;G may be associated with resistance to a 1,25 (OH) 2 D 3 based therapeutic regimen
Engraftment Syndrome following Hematopoietic stem cell transplant: A retrospective review of 70cases.
Authors: Adwaita Anant Gore, Vipul Sheth, Amit Ghanekar, Reetu Jain, Tapan K Saikia
Journal: Journal of Clinical Oncology (2015)

e18010 Background: Engraftment syndrome (ES) is increasingly observed in patients who receive auto--‐SCT. To investigate clinical criteria for ES diagnosis and analyze the risk factors for this complication, we reviewed 70 consecutive peripheral blood Autologous‐SCT (Lymphoma and Myeloma) performed during the past 6 years at a single tertiary care centre in Mumbai. Methods: Retrospective analysis of 70 cases of HDCT and ASCT from Single center in Mumbai was performed as per Maiolino and Spitzer criteria for ES. Results: A total of 15 patients presented with clinical symptoms and signs suggestive of ES with an incidence of 21.4%. Out of 15 patients, 8 were males and the median age was 30 years (range 18- 54). 7 patients were in early phase(complete response), 6 were in intermediate phase(partial response) and 2 were in the advanced phase prior to transplant. PBSCs were obtained after mobilization with GCSF (n = 5, 33%) or chemotherapy and GCSF (n = 3, 20%) or with Plerixafor and GCSF (n = 7, 47%) patients. 13 (86%) and 4 (26 %) could be diagnosed with ES using the Maiolino criteria(MC) and the Spitzer criteria (SC), respectively. The SC were less sensitive. The median duration of antibiotic in patients with ES was 10days (5‐19) and median duration of hospital stay was 19 days (11‐29). All patients improved after treatment with corticosteroids. We did not have any mortality or long term morbidity. Conclusions: Our study shows that engraftment syndrome is common in Autologous transplant setting. Maiolino criteria to diagnose ES is more sensitive in our setting. If detected and treated early there is not much morbidity or mortality related to ES.
Comparative analysis of 1% lymphazurin versus 1% methylene blue for sentinel lymph node mapping in early stage breast cancer.
Authors: Lindsay Berbiglia, Sukamal Saha, Gerard Paez, Jill Gernand, Linda Lawrence, Chris Conlin, Tomy Paul Kalapparambath, David Wiese
Journal: Journal of Clinical Oncology (2015)

e12055 Background: Sentinel lymph node mapping (SLNM) is the standard for staging clinically node negative (-ve LN) breast cancer (BrCa) patients (pts). Lymphazurin (L) has been the most commonly used blue dye for SLNM, but 1% methylene blue (M), have also been used. We sought to compare the efficacy, safety and equivalency of L vs M. Methods: Only pts with early (Tis, T1, T2) BrCa with clinically –ve LN from 1997-2014 underoing SLNM with either L or M were included. SLNM was performed with either L or M injected intraparenchymal, intradermal and subareolar. SLNs were ultrastaged by H&E and IHC. Results: A total of 298 pts with L and 353 pts with M were included. The majority of pts (64%) had T1 tumors. Overall the success rate of both dyes was >99%. No. of SLN/pt was less for L 2.2, vs 2.9 for M, but nodal positivity was higher, 15%, for L vs. 9% for M. There was one case of skip metastasis for both L and M. Overall, L had a higher complication rate (18%) than M (15%), including 2 pts with anaphylaxis. The majority of complications for M were mostly wound related with skin necrosis (3%) at the subdermal injection site. This was prevented subsequently by excising the injection site. Overall the cost of L was much higher than M. (Table) Conclusions: L and M are equally effective for successful SLNM in early stage BrCa. Absence of anaphylaxis, lack of drop in pulse oximetry and lower cost make M more desirable for SLNM in BrCa pts. <b>Comparison of methylene blue and lymphazurin for SLNM in early-stage breast cancer</b>. Category L M p-value No. pts 298 353 -- Average age (yrs) 61.94 63.55 0.1042 Tis disease 37 63 0.071 T1 disease 192 228 0.999 T2 disease 69 62 0.094 Average SLN/pt 2.22 2.89 <0.001 No. additional LN/pt 4.48 2.84 <0.001 Nodal positivity 14.93% 8.85% <0.001 Success rate 99.66% 99.72% 0.999 Skip metastasis 1.49% 1.37% 0.999 Avg cost/pt $815 $75 -- Complications: 18.12% 14.73% 0.289 Wound infection 2.68% 2.27% 0.802 Wound breakdown/nonhealing 1.68% 3.40% 0.220 Seroma 1.68% 6.23% 0.005 Hematoma 0% 0.28% 0.999 Skin necrosis 0% 2.55% 0.005 Blue hives 1.34% 0% 0.043 Pulse ox drop >5% 10.07% 0% <0.001 Anaphylaxis 0.67% 0% 0.209 [footer] L: 1% Lymphazurin (isosulfan blue), M: 1% Methylene blue. Skip mets = false negative/(false negative + true positive) [ /foooter]
Oxaliplatin-based regimen as neoadjuvant chemotherapy for Chinese patients with advanced gastric cancer: Preliminary results of a phase II study
Authors: J.-F. Ji, Z. Yu, X. N. Zhong, X. J. Wu, Q. Wu, Z. D. Bu, Y. Wang
Journal: Journal of Clinical Oncology (2004)

4184 Background: Gastric cancer is the first cause of death per cancer in China, with more than 160,000 deaths/year. At time of resection, 75–85% of gastric cancer (GC) patients (pts) are expected to have nodal involvement and are at high risk of postoperative relapse. A Phase-II trial was conducted to evaluate the benefits of surgery combined with Oxaliplatin (OXA)-based regimen as neoadjuvant and adjuvant chemotherapy, on the survival of pts with locally advanced disease. Methods: 15 pts (Stage IIIb or IV) have been enrolled by now. All pts had histologically proven gastric adenocarcinoma and no previous palliative chemotherapy. Median age: 59 years (33–69 years), male/female ratio: 10/5, performance status: 0–2. Pts received OXA 130 mg/m2 3H-infusion day 1, leucovorin (LV) 200 mg/m2 (2H-infusion) followed by 5FU 400mg/m2 (bolus) and 5FU 2.5g/m2 (22h-continuous infusion) day 1, repeated every 3 weeks. Efficacy was evaluated after 2 cycles. Results: All pts are evaluable for response with a more than 50% tumor reduction in 7 of 15 (46.7%)pts, SD was observed in 6 pts (40.0%) and PD in 2(13.3%).14 of 15 pts received a total 6 cycles (pre-op +or- post-op) of chemotherapy and all 15 pts came to surgery after receiving 2–6 cycles. OXA-5FU/LV was general well tolerated. The most common toxicity was Grade (Gr) 2 or 3 neutropenia and diarrhea or Gr 2 nausea/vomiting, No patients experienced Gr 4 toxicity. Neutropenic fever was not observed. An R0 curative resection was possible in 7 pts. There were no postoperative mortalities and no treatment related deaths; 14 of 15 pts are surviving (2 to 24 months) and one PD pt died of disease 2 months after surgery. Pathologic examinations of operative samples showed significant chemotherapy-induced changes in 6 pts. The trial is still open and more mature data will be available at the meeting. Conclusions: In view of the favorable response rate and toxicity profile, this protocol will be further assessed in a multicenter phase II trial. No significant financial relationships to disclose.
Chemokine interactome mapping enables tailored intervention in acute and chronic inflammation
Authors: Philipp von Hundelshausen, Stijn M. Agten, Veit Eckardt, Xavier Blanchet, Martin M. Schmitt, Hans Ippel, Carlos Neideck, Kiril Bidzhekov, Julian Leberzammer, Kanin Wichapong, Alexander Faussner, Maik Drechsler, Jochen Grommes, Johanna P. van Geffen, He Li, Almudena Ortega-Gomez, Remco T. A. Megens, Ronald Naumann, Ingrid Dijkgraaf, Gerry A. F. Nicolaes, Yvonne Döring, Oliver Soehnlein, Esther Lutgens, Johan W. M. Heemskerk, Rory R. Koenen, Kevin H. Mayo, Tilman M. Hackeng, Christian Weber
Journal: Science Translational Medicine (2017)

Chemokines orchestrate leukocyte trafficking and function in health and disease. Heterophilic interactions between chemokines in a given microenvironment may amplify, inhibit, or modulate their activity; however, a systematic evaluation of the chemokine interactome has not been performed. We used immunoligand blotting and surface plasmon resonance to obtain a comprehensive map of chemokine-chemokine interactions and to confirm their specificity. Structure-function analyses revealed that chemokine activity can be enhanced by CC-type heterodimers but inhibited by CXC-type heterodimers. Functional synergism was achieved through receptor heteromerization induced by CCL5-CCL17 or receptor retention at the cell surface via auxiliary proteoglycan binding of CCL5-CXCL4. In contrast, inhibitory activity relied on conformational changes (in CXCL12), affecting receptor signaling. Obligate CC-type heterodimers showed high efficacy and potency and drove acute lung injury and atherosclerosis, processes abrogated by specific CCL5-derived peptide inhibitors or knock-in of an interaction-deficient CXCL4 variant. Atheroprotective effects of CCL17 deficiency were phenocopied by a CCL5-derived peptide disrupting CCL5-CCL17 heterodimers, whereas a CCL5 α-helix peptide mimicked inhibitory effects on CXCL12-driven platelet aggregation. Thus, formation of specific chemokine heterodimers differentially dictates functional activity and can be exploited for therapeutic targeting.
Breast cancer in young women: A single center study.
Authors: Joanna Rodriguez, Kimberly Limentani, Jocelyn Andrel-Sendecki, Terry Hyslop, Massimo Cristofanilli, Rebecca J. Jaslow, Tiffany P. Avery, Edith P. Mitchell
Journal: Journal of Clinical Oncology (2014)

595 Background: Breast Cancer among young women is on the rise. It is estimated there will be up to 13,000 new cases this year in this age group. There are no screening guidelines in place for women younger than 40 years old. Breast cancer in this age group is associated with higher morbidity and mortality compared to older women, thus the impact of the disease is significant. Methods: We performed a retrospective chart review of women younger than 45 years old diagnosed and treated for breast cancer at Thomas Jefferson University from 1998-2012. Patients were stratified by age, stage, disease subtype (triple negative; HR+/Her2-;HR+/Her2 +; HR-/Her2+), race, and BMI. Descriptive analysis was performed. Results: Seven hundred and thirty three patients younger than 45 years old were reviewed from 1998-2012.The majority of patients were Caucasian (74%), followed by African American (14%), Asian (1.36%) and Hispanic (.13%). The analysis demonstrated that ER negative disease was found in 20% of patients, with the percentage increasing over the study period. From 1998-2006, 34% of patients were diagnosed with ER negative disease but from 2008-2012, 44.12% of patients were diagnosed with this type of breast cancer. This trend in incidence was not observed in the HER2 positive subtype set which remained stable at 21%. Moreover, the analysis found that there has been an increase in patients presenting with locally advanced disease (clinical stages III/IV). From 2007-2012 stage III/IV disease was documented in 29% of patients as compared to 13.5% of patients from 1998-2006. Conclusions: This retrospective study indicates that breast cancer diagnosed in women younger than 45 years is increasingly associated an aggressive clinical and molecular subtype. Delay in diagnosis has been a concern among this age group given the lack of screening guidelines. Furthermore, our data shows an increase in ER negative disease in recent years, suggesting a possible shift in tumor biology as well. More awareness and screening programs to both practitioners and young women should be implemented.
Treatment strategies in recurrent esophageal or junctional cancer after neoadjuvant therapy followed by esophagectomy.
Authors: Rogier Butter, Sjoerd M Lagarde, Maarten CJ Anderegg, Suzanne S Gisbertz, Sybren L. Meijer, Maarten Hulshof, Jacques Bergman, Mark I van Berge Henegouwen, Hanneke W.M. Van Laarhoven
Journal: Journal of Clinical Oncology (2015)

e15024 Background: Recurrent disease (RD) after potentially curative treatment for esophageal or junctional cancer is common and survival after recurrence is poor. Potentially curative strategies are possible in limited occasions and palliative systemic therapy or supportive care are often the only therapies possible. Little is known about survival after recurrence and factors influencing treatment success. We aimed to assess the recurrence patterns and overall survival (OS) of patients who developed RD after curative treatment. Methods: Patients with RD of esophageal or junctional cancer between 1994 and 2014 after potentially curative esophagectomy preceded by neoadjuvant chemo(radio)therapy were included in this retrospective cohort study. A logistic regression analysis was performed to assess predictive factors for receiving treatment aimed at radical tumor eradication. Results: Recurrence was diagnosed in 219 of 503 patients (43.5%). 212 of 219 patients (96.8%) were evaluable for dissemination patterns and 204 (93.2%) for treatment strategies. Locoregional failure (LRF) was diagnosed in 23 patients (10.5%) and distant metastases (DM) in 189 patients (86.3%). Patients with LRF had a median OS of 4.9 months (CI 95%, 0.0-15.6) and patients with DM 2.9 months (CI 95%, 2.1-3.6), p < 0.05. Treatment aimed at radical tumor eradication was applied in 28 patients (13.7%), 11 of whom had DM and 17 LRF. Patients who were free of DM and had a longer interval between surgery and recurrence had a higher chance of receiving treatment aimed at radical tumor eradication (OR 8.7; CI 95%, 3.3-22.6; p < 0.05). Palliative treatment was applied in 94 patients (46,1%), 88 of whom had DM and 6 LRF. Supportive care was applied in 82 patients (40.2%), 6 of whom had DM and 73 LRF. Median OS was 13.6 months (CI 95%, 6.0-21.3) in radically treated patients, 4.7 months in palliative treated patients (CI 95%, 3.9 to 5.5) and 1.1 months in patients who received supportive care (CI 95%, 0.6-1.5), p < 0.05. Conclusions: Treatment aimed at radical eradication of RD is possible, even when DM are involved, and is associated with better survival compared to palliative treatment or best supportive care.