tbuckley/cabot-search huggingface dataset:
IMCT-10A PHASE I DOSE ESCALATION STUDY TO TEST THE SAFETY OF INTRATUMORAL ADOPTIVE IMMUNE THERAPY WITH AlloCTL IN RECURRENT GLIOMA PATIENTS
Authors: Michelle Hickey, Horacio Soto, Janet Treger, Kate Erickson, Colin Malone, Edward Ha, Emma Young, Robert Prins, Linda Liau, Carol Kruse
Journal: Neuro-Oncology (2015)

In a Phase 1 dose escalation study we evaluated the safety, feasibility, toxicity, and survival of patients treated with allogeneic cytotoxic T lymphocytes and recombinant IL-2 (alloCTL, rIL-2) infusion administered to the resection cavity of patients with recurrent glioma (WHO grade III or IV). AlloCTL are generated when gamma-irradiated lymphoblasts from the brain tumor patient stimulate the proliferation of peripheral blood mononuclear cells (PBMC) isolated from an HLA-disparate healthy donor in ex vivo culture via one-way mixed lymphocyte reaction. Nine patients were treated on the protocol and received a range of 0.5-5 cycles of therapy. Patients and donors were mismatched at a minimum of 2 HLA A, B, DR loci. Infusates were at least 30% CD3+. Cytotoxicity of alloCTL against patient PBMC ranged from 21.0-84.4% at a 30:1 effector to target ratio. The ratio of CD4/CD8 T cells averaged 1.12 (range 0.14-2.95). In vitro restimulation of alloCTL with patient lymphoblasts allowed for quantitation of immune cell subset proliferation and production of IFN-γ. Adverse events were noted at all three dose levels tested, and were primarily limited to Grade 1-2. Grade 3-4 events were noted only at dose levels 2 and 3. One patient experienced a dose limiting toxicity characterized by Grade 3 fatigue, arthralgia, headache, and non-infectious meningitis. Patient serum samples were collected during the course of therapy to determine Th1/Th2 cytokine profiles using Luminex multiplex analysis. Tumor progression was evident in 8/9 patients resulting in removal from the clinical trial. Median overall survival from the time of inclusion into the study was 8.8 months (range- 3.6-35.7 months). Two patients are still alive at greater than 35.7 and 16.4 months. The results suggest that alloCTL infusion is safe, feasible, and may warrant further study based on the clinical results.
Changes in the Disparity of HIV Diagnosis Rates Among Black Women — United States, 2010–2014
Authors: Donna Hubbard McCree, Madeline Sutton, Erin Bradley, Norma Harris
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

In 2015, black women represented 61% of human immunodeficiency virus (HIV) diagnoses among women (1). HIV diagnosis rates among women declined during 2010-2014 (1); however, whether the decline resulted in a decrease in the disparities between black women and Hispanic and white women was unknown. To assess whether a change in disparities occurred, CDC used three different measures of disparity: 1) the absolute rate difference (the difference between the group with the lowest rate and the group with the highest rate) (2); 2) the diagnosis disparity ratio* (the ratio of the difference between the group rate and the overall population rate to the overall rate); and 3) the Index of Disparity (the average of the differences between rates for specific groups and the total rate divided by the total rate, expressed as a percentage) (3). The absolute rate difference between black women and white women decreased annually, from 36.9 in 2010 to 28.3 in 2014. The diagnosis disparity ratio for black women decreased from 1.7 in 2010 to 1.2 in 2014. The Index of Disparity increased during 2010-2011, and then decreased each year during 2012-2014. Although disparities still exist, these findings indicate improvement. Expanding access to biomedical and behavioral interventions and research guided by social and structural determinants frameworks could close the remaining gap.
Non-Tropical Sprue: A Study in Idiopathic Steatorrhoea.
Journal: JAMA (1933)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Effect of the pollen season on nasal mast cells:: Authors' reply
Authors: M Viegas, E Gomez, D Gatland, R J Davies
Journal: BMJ (1987)

AumoRs' REPLY-As Drs -Brown and Edwards suggest, the amounts ofsodium nitroprusside used in our two groups do seem to differ.We would point out, however, that.theuse of sodium nitro-
Human Pharmacokinetics of AC220, a Potent and Selective Class III Receptor Tyrosine Kinase Inhibitor.
Authors: Jorge Cortes, James M. Foran, Marcel P. Devetten, Francis J. Giles, Joyce James, Patrick P. Zarrinkar, Michael H. Silverman, Kerry A. Kelly, Norman M. Padre, Shripad Bhagwat, Wendell Wierenga
Journal: Blood (2007)
Re: Alessandro Morlacco, John C. Cheville, Laureano J. Rangel, Derek J. Gearman, R. Jeffrey Karnes. Adverse Disease Features in Gleason Score 3 + 4 “Favorable Intermediate-risk” Prostate Cancer: Implications for Active Surveillance. Eur Urol 2017;72:442–7
Authors: Chen Du, Hui Chen, Changfu Li
Journal: European Urology (2017)
Dclk1, a tumor stem cell marker, regulates pro-survival signaling and self-renewal of intestinal tumor cells
Authors: Parthasarathy Chandrakesan, Jiannan Yao, Dongfeng Qu, Randal May, Nathaniel Weygant, Yang Ge, Naushad Ali, Sripathi M. Sureban, Modhi Gude, Kenneth Vega, Eddie Bannerman-Menson, Lijun Xia, Michael Bronze, Guangyu An, Courtney W. Houchen
Journal: Molecular Cancer (2017)

More than 80% of intestinal neoplasia is associated with the adenomatous polyposis coli (APC) mutation. Doublecortin-like kinase 1 (Dclk1), a kinase protein, is overexpressed in colorectal cancer and specifically marks tumor stem cells (TSCs) that self-renew and increased the tumor progeny in Apc Min/+ mice. However, the role of Dclk1 expression and its contribution to regulating pro-survival signaling for tumor progression in Apc mutant cancer is poorly understood.We analyzed DCLK1 and pro-survival signaling gene expression datasets of 329 specimens from TCGA Colon Adenocarcinoma Cancer Data. The network of DCLK1 and pro-survival signaling was analyzed utilizing the GeneMANIA database. We examined the expression levels of Dclk1 and other stem cell-associated markers, pro-survival signaling pathways, cell self-renewal in the isolated intestinal epithelial cells of Apc Min/+ mice with high-grade dysplasia and adenocarcinoma. To determine the functional role of Dclk1 for tumor progression, we knocked down Dclk1 and determined the pro-survival signaling pathways and stemness. We used siRNA technology to gene silence pro-survival signaling in colon cancer cells in vitro. We utilized FACS, IHC, western blot, RT-PCR, and clonogenic (self-renewal) assays.We found a correlation between DCLK1 and pro-survival signaling expression. The expression of Dclk1 and stem cell-associated markers Lgr5, Bmi1, and Musashi1 were significantly higher in the intestinal epithelial cells of Apc Min/+ mice than in wild-type controls. Intestinal epithelial cells of Apc Min/+ mice showed increased expression of pro-survival signaling, pluripotency and self-renewal ability. Furthermore, the enteroids formed from the intestinal Dclk1+ cells of Apc Min/+ mice display higher pluripotency and pro-survival signaling. Dclk1 knockdown in Apc Min/+ mice attenuates intestinal adenomas and adenocarcinoma, and decreases pro-survival signaling and self-renewal. Knocking down RELA and NOTCH1 pro-survival signaling and DCLK1 in HT29 and DLD1 colon cancer cells in vitro reduced the tumor cells' ability to self-renew and survive.Our results indicate that Dclk1 is essential in advancing intestinal tumorigenesis. Knocking down Dclk1 decreases tumor stemness and progression and is thus predicted to regulate pro-survival signaling and tumor cell pluripotency. This study provides a strong rationale to target Dclk1 as a treatment strategy for colorectal cancer.
A Polymorphism In Interferon Gamma Gene Impacts the Extent of Joint Damage In Patients with Severe Hemophilia
Authors: Giridhara Rao Jayandharan, Aaron Chapla, Sukesh C Nair, Kavitha Lakshmi, Auro Viswabandya, Vikram Mathews, Alok Srivastava
Journal: Blood (2010)
Interest of the Association Azacitidine-Lenalidomide As Front Line Therapy in High-Risk Myelodysplasia (MDS) or Acute Myeloid Leukemia (AML) with Complex Karyotype
Authors: Elodie Scherman, Sandra Malak, Christine Perot, Norbert C. Gorin, Marie T Rubio, Françoise Isnard
Journal: Blood (2011)
Osteoblastic Cells and the Hematopoietic Microenvironment: The Notch ligand Jagged1 Is Increased in Osteoblastic Stromal Cells by Parathyroid Hormone (PTH)Treatment.
Authors: Laura M. Calvi, Jonathan M. Weber, Monica L. Guzman, Christina A. Christianson, Laurie M. Milner, Craig T. Jordan
Journal: Blood (2004)
Phase I dose-finding study of capecitabine (X) with escalating irinotecan (I) and oxaliplatin (O) in patients (pts) with previously treated solid tumors
Authors: E. Samantas, S. K. Rigatos, M. Triantafillis, S. Kourtis, G. Koutsourakis, K. Papanikitas, A. Konstantinopoulou, V. Koussoulas, G. Aravantinos
Journal: Journal of Clinical Oncology (2005)

3543 Background: The oral fluoropyrimidine X is highly active and well tolerated in combination with either I or O as first- or second-line treatment in pts with metastatic colorectal cancer and other tumor types. As recent evidence suggests that 3 active agents are better than 2 in pts with metastatic disease, we evaluated the combination of X, I and O (XIROX 800 regimen) in pts with previously treated solid tumors. The main aim was to determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of this novel combination. Methods: Eligible pts had gastrointestinal tract tumors and were heavily pretreated. Pts received X (orally bid, d1–14), and escalating doses of I (i.v. d1) and O (i.v. d1) every 3 weeks as shown in the table. DLT was defined as any grade 4 hematological adverse event or any grade 3/4 non-hematological event. MTD was defined as the dose level below that at which DLTs occurred. At least 3 pts were treated at each dose level and 3 more pts were enrolled at the level at which DLT was observed. Results: 21 pts (11 women, 10 men) were enrolled, 3 each at dose levels 1–5, and 6 pts at dose level 6. Median age was 66 years (range 32–77), 40% had received second-line chemotherapy and 60% had received >2 lines of chemotherapy. Among the first 3 pts entered at dose level 6, 1 developed grade 4 febrile neutropenia. 3 more pts entered at the same dose level: 1 presented with grade 4 gastrointestinal adverse events. Because of the DLTs at dose level 6, we recommend the previous dose level (level 5) as appropriate for further evaluation. In terms of response, we have observed 1 CR in gastric cancer, 1 PR in gastric cancer and 5 PRs in colon cancer in second-/third-line settings. Conclusion: The XIROX 800 regimen is well tolerated in previously treated pts. The recommended doses for further evaluation in phase II studies are: X (800mg/m2 bid d1–14), I (140mg/m2 d1) and O (80mg/m2 d1), every 3 weeks. No significant financial relationships to disclose.
Feasibility study of neoadjuvant chemoradiotherapy with cisplatin plus 5-fluorouracil and elective nodal irradiation for stage II/III esophageal squamous cell carcinoma.
Authors: Takashi Kojima, Jun Hashimoto, Ken Kato, Yoshinori Ito, Hiroyasu Igaki, Hiroyuki Daiko, Masakatsu Onozawa, Yasuo Hamamoto, Hideaki Shimizu, Susumu Katano, Hiroki Hara, Yoichi Tanaka, Yoshihiro Saito
Journal: Journal of Clinical Oncology (2012)

130 Background: Based on the JCOG 9907 trial results, neoadjuvant chemotherapy with cisplatin (CDDP) plus 5-fluorouracil (5-FU) is considered a standard treatment for stage II/III esophageal squamous cell carcinoma (ESCC) in Japan. However, patient survival remains unsatisfactory. We conducted a feasibility study of neoadjuvant chemoradiotherapy (NeoCRT) with CDDP plus 5-FU and elective nodal irradiation for stage II/III ESCC. Methods: Eligibility criteria included clinical stage II/III (UICC 6th, non-T4) ESCC, PS 0-1, and age 20–75 years. Chemotherapy consisted of 2 courses of 5-FU infusion (1000 mg/m 2 , days 1–4) and a 2-h CDDP infusion (75 mg/m 2 , day 1), with a 4-week interval. Radiotherapy was concurrently administered to a total 41.4 Gy in 23 fractions for primary tumor, metastatic lymph nodes and regional lymph nodes. After completion of CRT, transthoracic esophagectomy with extensive lymphadenectomy (&gt;D2) was performed. The primary endpoint was the completion rate of NeoCRT and R0 resection. Results: From July 2010 to June 2011, 33 patients were enrolled, including 2 ineligibles. In 31 eligible patients, the median age was 63 years (range, 40–73); male/female: 28/3; PS0/1: 19/12; cStage IIA/IIB/III: 2/10/19. During CRT, the most common grade 3 or 4 toxicities were leukopenia (65%), neutropenia (65%), anemia (13%), thrombocytopenia (13%), febrile neutropenia (13%), anorexia (16%), esophagitis (16%), and hyponatremia (16%). In total, 31 patients (100%) underwent CRT and 25 (81%) underwent surgery; 1 patient (3%) did not undergo surgery due to disease progression, and the other 5 patients (16%) are scheduled for surgery. Among patients who underwent surgery, there was 1 treatment-related death, and the incidence of operative morbidity was similar to that in previous studies. According to RECIST, the overall response rate was 63% after CRT completion. Pathological complete response was achieved in 11 patients (44%) who underwent esophagectomy. Conclusions: NeoCRT was well tolerated and appears to be highly promising. The randomized controlled trial compared with neoadjuvant chemotherapy is needed and will be started.
A phase II study of axitinib in patients with recurrent or metastatic nasopharyngeal carcinoma (NPC).
Authors: Edwin Pun Hui, Brigette Ma, Frankie Mo, Michael KM Kam, Stephen Lam Chan, Herbert H. F. Loong, Rosalie Ho, Sing Fai Leung, Ann Dorothy King, Ki Wang, Anil Tejbhan Ahuja, Charles Chan, Connie WC Hui, Chi Hang Wong, Anthony T. C. Chan
Journal: Journal of Clinical Oncology (2015)

6031 Background: Axitinib has demonstrated potent in vitro and in vivo activity in preclinical models of NPC [Cancer Res 2012;72(8 Suppl):Abstract 1373]. We aimed to validate the findings in NPC patients (pts). Methods: This is an open label, single arm, phase II study of axitinib monotherapy in recurrent or metastatic NPC pts who failed at least one line of platinum based chemotherapy. Pts with Eastern Cooperative Group (ECOG) 0-1, adequate organ functions, and without local recurrence or tumor close to major vessels, received a starting dose of axitinib at 5 mg twice daily in continuous 4-weeks cycles until progression or unacceptable toxicity. Primary endpoint was clinical benefit rate (CBR), defined as % of pts achieving complete response (CR), partial response (PR) or stable disease (SD) by RECIST for > 12 weeks. Secondary endpoints included time to progression (TTP), overall survival (OS), safety and plasma axitinib pharmacokinetics (PK). Simon’s Minimax two-stage phase II design (P0 = 0.50, P1 = 0.70, type I error 0.05, power 80%) was used to calculate the sample size (n = 37). Results: 37 pts were accrued. Median age was 53 (22-74). M:F = 32:5. Pts received a median of 3 lines of prior chemotherapy (range 1-6). 36 pts (97%) had prior radiotherapy and 2 pts (5%) had prior surgery for NPC. Axitinib treatment was delivered for a median of 4 cycles (range 1-21, 3 pts were still on treatment), with 15 pts (41%) received ≥ 6 cycles, 6 pts ≥ 10 cycles and 2 pts ≥ 18 cycles. 10 pts had dose reductions and 8 pts had dose escalations. Of 34 pts evaluable for response, CBR = 73.5% (95% CI: 60.7%-86.3%; 1 confirmed PR, 4 unconfirmed PR, 20 SD >12 weeks). Median TTP 5.4 months (95% CI: 3.9-5.9). Median OS 10.4 months (6.5-19.0). 1-year survival rate 43.6%. Treatment-related adverse events (AEs) by CTCAE v3, all grades (Gr) in ≥ 25% of pts: hypothyroidism 46% (Gr 3: 3%), fatigue 43% (Gr 3: 3%), hand-foot 43% (Gr 3: 3%), hypertension 32% (Gr 3: 5%), diarrhea 27% (Gr 3: 3%), mucositis 27% (Gr 3: 0%). Gr 3 AEs were uncommon (≤ 5%) and there was no Gr 4 or above treatment-related AE. All hemorrhages (16%) were Gr 1. PK data will be presented. Conclusions: Single agent axitinib achieved prolonged disease control with a good safety profile in this cohort of heavily pretreated NPC pts. Clinical trial information: NCT01249547.
EPIDEMIOLOGY OF MUSCLE INJURIES IN HONG KONG PROFESSIONAL FOOTBALL
Authors: Justin Wai-Yuk Lee, Kam-Ming Mok, Patrick Shu-Hang Yung
Journal: British Journal of Sports Medicine (2017)

Background Muscle injuries constitute a large percentage of all injuries in football. Objective The aim of this study was to investigate the incidence and nature of muscle injuries in male professional footballers. Design Prospective cohort study design. Setting Teams from the first division of a professional football league. Patients (or Participants) Seven football teams, comprising 152 players, were followed prospectively. Main Outcome Measurements Team medical staff recorded individual player exposure and time-loss injuries. A muscle injury was defined as ‘‘a traumatic distraction or overuse injury to the muscle leading to a player being unable to participate fully in training or match play.’' Results In total, 114 muscle injuries were registered. On average, a player sustained 0.75 muscle injuries per season. A squad of 25 players can thus expect about 19 muscle injuries per season. Muscle injuries constituted 38.5% of all injuries. Sixty-eight percent of all muscle injuries were muscle strain injuries. The four most commonly strained muscle groups were adductors/groin (40%), hamstring (35%), calf muscles (16%) and quadriceps (9%). Sixteen percent of the muscle injuries were reinjuries. The incidence of muscle injury is increased with age. Conclusions Muscle injuries are a substantial problem for players and their clubs. They constitute more than one-third of all time-loss injuries in men's professional football and affect the four big muscle groups in the lower limbs.
Circulating Gut- or Skin-Homing Regulatory T Cells (Tregs) Predict Whether Acute Graft-Versus-Host Disease (aGVHD) Occurs in Gut or Skin Following Allogeneic Stem Cell Transplantation (ASCT)
Authors: Brian Engelhardt, Madan Jagasia, Michael T Rock, Nikki L Bratcher, John P. Greer, Aixiang Jiang, Adetola A. Kassim, Pengcheng Lu, Friedrich Schuening, James E Crowe
Journal: Blood (2008)
A Brainstem-Spinal Cord Inhibitory Circuit for Mechanical Pain Modulation by GABA and Enkephalins
Authors: Amaury François, Sarah A. Low, Elizabeth I. Sypek, Amelia J. Christensen, Chaudy Sotoudeh, Kevin T. Beier, Charu Ramakrishnan, Kimberly D. Ritola, Reza Sharif-Naeini, Karl Deisseroth, Scott L. Delp, Robert C. Malenka, Liqun Luo, Adam W. Hantman, Grégory Scherrer
Journal: Neuron (2017)
Vincristine sulfate liposomes injection (VSLI) “bridging” to potentially curative hematopoietic stem cell transplantation (HSCT) in adults with Philadelphia chromosome negative (Ph-) acute lymphoblastic leukemia (ALL).
Authors: G. J. Schiller, S. E. Coutre, M. L. Larson, D. Ben Yehuda, P. Venugopal, S. Goldberg, G. L. Messerschmidt, J. Silverman, S. R. Deitcher, H. Kantarjian
Journal: Journal of Clinical Oncology (2011)

6527 Background: In a phase II, multi-national study (RALLY Trial; NCT00495079), 65 adults (median age 32 yrs, range 19 to 83) with Ph-ALL in second or greater relapse or who had progressed after two or more prior lines of treatment received single-agent, VSLI (Marqibo) 2.25 mg/m2 (without dose cap) IV weekly. All subjects were ineligible for immediate HSCT due to refractoriness to prior HSCT or the most recent salvage attempt, poor performance status, and/or insufficient anticipated lifespan. Methods: “Bridging” to HSCT was assessed as a pre-defined study secondary endpoint. Results: Overall response rate was 35% (95% CI: 24-48) with a 20% (95% CI: 11-32) complete response (CR) plus CR with incomplete hematologic recovery (CRi) rate. VSLI, despite delivering individual (2.8-5.5 mg) and cumulative (up to 70.1 mg) dose-intense VCR, had a similar safety profile to that reported for standard VCR. VSLI enabled bridging to HSCT in 11 of 65 (17%) subjects. Seven of the 11 (64%) subjects had undergone at least one pre-VSLI HSCT. Five of the 11 subjects were in CR/CRi at the time of post-VSLI HSCT. Three of 11 subjects remain alive at greater than 28, 33, and 35 mos, respectively, after post-VSLI HSCT. Five of 11 subjects relapsed and died following post-VSLI HSCT. Three of 11 subjects died of HSCT-related complications. All 11 subjects lived for greater than 100 days after post-VSLI HSCT. Conclusions: VSLI produced rapid CR/CRi or disease stabilization and a meaningful “bridge” to HSCT in 11 of 65 (17%) heavily pre-treated near end-stage adults with ALL. Long-term survival (greater than 12 mos) was achieved in 27% of those able to receive post-VSLI HSCT. These unexpected outcomes that are important to patients may reflect the effectiveness of the dose intensification facilitated by VSLI compared to that provided by standard VCR. Post-VSLI HSCT subject characteristic CR/CRi, N = 5 median (range) Non-CR/CRi, N = 6 median (range) Interval from 1st VSLI to HSCT, mos 2.7 (1.5-3.2) 5.0 (2.2-9.0) Cumulative VSLI exposure, mg 30.3 (15.8-41.4) 26.8 (4.0-49.0) OS following 1st VSLI, mos 8.6 (5.3-27.7+) 9.0 (6.3-34.9+)