tbuckley/cabot-search huggingface dataset:
Comparative effectiveness of treatment strategies for urothelial cancer of the bladder (UCB) with clinical lymph node involvement (cN+).
Authors: Matt D. Galsky, Kristian Stensland, John Sfakianos, Reza Mehrazin, Michael Diefenbach, Che-Kai Tsao, Paolo Boffetta, William K. Oh, Madhu Mazumdar, Bart Ferket
Journal: Journal of Clinical Oncology (2016)

4530 Background: Patients (pts) with cN+ UCB are high risk, but potentially curable. Such pts are excluded from neoadjuvant chemotherapy (chemo) trials and pooled with pts with distant metastases in 1st line chemo trials not suited to define the role of combined modality therapy. To address this evidence void, we performed a comparative effectiveness analysis. Methods: We included cTanyN1-3M0 UC pts from the National Cancer Database (2003-2012) treated with multi-agent chemo and/or cystectomy (cyst). We used multi-state survival analysis allowing for delayed entry to assess overall survival (OS) according to various treatment strategies. Effectiveness was estimated with multivariable adjustment for tumor-, patient-, and facility-level characteristics. To disentangle the effectiveness of specific approaches, we additionally censored for adjuvant chemo and adjusted for pathological stage. Results: Among 1,756 pts (cN1=48%, cN2=45%, cN3=7%), 1,104 underwent cyst and 652 were treated with chemo alone. Of the cyst pts, 363 received pre-op chemo and 328 received adjuvant chemo. Crude 5-year OS for cyst alone, chemo alone, pre-op chemo, and adjuvant chemo was 19%, 13%, 31%, and 26%, respectively. Multivariable multi-state models censored for start of adjuvant chemo demonstrated that pre-op chemo improved OS, an effect associated with improved pathological stage (Table). Survival of pts treated with chemo alone was similar to pts undergoing cyst alone, while adjuvant chemo independently improved OS (Table). Conclusions: In this large observational cohort, a sizeable subset of pts with cN+ UCB achieved durable disease control. Treatment with combined modality therapy, with chemo administered pre- or post-cyst, was associated with significantly improved OS. Multivariable adjusted hazard ratios (HR) for OS (reference: cyst +/- adjuvant). Analysis Treatment HR (95% CI) Overall Chemo alone 1.34 (1.18-1.53) Pre-op chemo 0.93 (0.78-1.11) Censored for adjuvant chemo Chemo alone 1.15 (0.99-1.35) Pre-op chemo 0.80 (0.65-0.97) Censored for adjuvant chemo, adjusted for path stage Pre-op chemo 1.14 (0.98-1.33) Adjusted for path stage Adjuvant chemo 0.69 (0.57-0.83)
334P Preliminary results of HKNPC-1001 trial to evaluate the role of induction TPF followed by weekly docetaxel and cetuximab in combination with intensity modulated radiotherapy for locally recurrent nasopharyngeal carcinoma
Authors: R.K. Ngan, W.T. Ng, D. Kwong, S. Tung, C.C. Yau, S.F. Leung, W.Y. Chan, M. Lung, A. Lee
Journal: Annals of Oncology (2015)
ATX-101 for reduction of submental fat: A phase III randomized controlled trial
Authors: Shannon Humphrey, Jonathan Sykes, Jonathan Kantor, Vince Bertucci, Patricia Walker, Daniel R. Lee, Paul F. Lizzul, Todd M. Gross, Frederick C. Beddingfield
Journal: Journal of the American Academy of Dermatology (2016)

ATX-101, an injectable form of deoxycholic acid, causes adipocytolysis when injected subcutaneously into fat.We sought to evaluate the efficacy and safety of ATX-101.In this phase III trial (REFINE-2), adults dissatisfied with their moderate or severe submental fat (SMF) were randomized to ATX-101 or placebo. Coprimary end points, evaluated at 12 weeks after last treatment, were composite improvements of 1 or more grades and 2 or more grades in SMF observed on both the validated Clinician- and Patient-Reported SMF Rating Scales. Other end points included magnetic resonance imaging-based assessment of submental volume, assessment of psychological impact of SMF, and additional patient-reported outcomes.Among those treated with ATX-101 or placebo (n = 258/treatment group), 66.5% versus 22.2%, respectively, achieved a composite improvement of 1 or more grades (Mantel-Haenszel risk ratio 2.98; 95% confidence interval 2.31-3.85) and 18.6% versus 3.0% achieved a composite improvement of 2 or more grades in SMF (Mantel-Haenszel risk ratio 6.27; 95% confidence interval 2.91-13.52; P < .001 for both). Those treated with ATX-101 were more likely to achieve submental volume reduction confirmed by magnetic resonance imaging, greater reduction in psychological impact of SMF, and satisfaction with treatment (P < .001 for all). Overall, 85.7% of adverse events in the ATX-101 group and 76.9% in the placebo group were localized to the injection site.Follow-up was limited to 44 weeks.ATX-101 is an alternative treatment for SMF reduction.
Abstract P4-16-02: A survival benefit from locoregional radiotherapy for node-positive and CMF treated breast cancer is most significant in Luminal A tumors
Authors: D Voduc, MCU Cheang, S Tyldesley, S Chia, K Gelmon, C Speers, TO Nielsen
Journal: Cancer Research (2012)

Abstract Background: Between 1978–1986, 318 premenopausal women treated with mastectomy for lymph node positive breast cancer, were randomized to CMF chemotherapy alone vs. CMF chemotherapy and adjuvant radiotherapy (RT) to the chest wall and regional lymph nodes. After 15 years of follow-up, post-mastectomy RT was associated with a statistically significant 29% relative risk reduction in mortality. Recent evidence suggests that Luminal A tumors, identified using hormone receptors and Ki67, have a particularly favorable prognosis. We retrospectively identified the Luminal A tumors from this clinical trial cohort to determine if the response to postmastectomy RT differed among Luminal A and non-Luminal A tumors. Methods: 203 archival breast tumor samples from this study were used to construct a tissue microarray. Luminal A tumors were identified using an immunopanel consisting of: estrogen receptor, progestorone receptor, Her2, and Ki67. Luminal A tumors were defined as either ER or PR positive, Her2 negative, and Ki67 &amp;lt; 14%. Kaplan-Meier estimates and the log-rank test were used to test the differences in locoregional relapse free survival (LRFS) and breast cancer specific survival (BCSS). Interaction between treatment and Luminal A/Non-luminal A were tested using Cox regression analysis. Results: The intrinsic subtype was successfully determined in 144 breast tumors, and 49 were classified as Luminal A (34%). Survival outcomes at 10 years are summarized in Table 1: Conclusion: Our study examines the outcome of Luminal A tumors in patients with higher risk (premenopausal and lymph node positive) breast cancer treated with CMF chemotherapy. We observed that both subjects with Luminal A tumors and non-Luminal A tumors appear to demonstrate improved locoregional control with post-mastectomy RT, although this was only significant for Luminal A tumors. The non-significant interaction test suggests that there is no observable difference in radiosensitivity in this limited study population. However, the improvement in BCSS with post-mastectomy RT was only significant in the subjects with Luminal A tumors, and the interaction test was statistically significant. Our results raise the possibility that patients with non-Luminal A breast tumors are at higher risk of occult metastatic disease at presentation, and may not derive a survival benefit with improved locoregional control in the setting of CMF chemotherapy. In contrast, locoregional control has a significant effect on survival with Luminal A tumors. Our study suggests that a favorable Luminal A diagnosis should not be a reason to omit regional radiotherapy in node positive patients, as it is this subgroup that may derive the greatest benefit. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-16-02.
Abstract 5079: Sunitinib suppresses ovarian cancer metastasis through the negative modulation of TGF-β-mediated epithelial-mesenchymal transition
Authors: Zibo Chen, Lin-lin Chang, Tian-yi Zhou, Dan-dan Wang, Ying Chen, Hong Zhu, Meidan Ying, Bo Yang, Qiao-jun He
Journal: Cancer Research (2016)

Abstract The mechanism of the negative regulation TGF-β mediated of epithelial-mesenchymal transition by sunitinib to inhibit ovarian cancer metastasis. We evaluated the inhibitory ability possessed by sunitinib against SKOV3 ovarian cancer cells motility by wound-healing and transwell assays. The results showed that sunitinib inhibited the migration of SKOV3 cells. The results obtained from wound-healing and transwell assays showed that sunitinib suppressed the motility of ovarian cancer SKOV3 cells in a concentration-dependent manner. In another,the effects of sunitinib on TGF-β-induced E-cadherin protein levels was assessed by western-blot, qRT-PCR and immunofluorescence assay. As a result, sunitinib attenuated the downregulation of E-cadherin protein level induced by TGF-β. Western-blot, qRT-PCR and immunofluorescence analyses displayed that the TGF-β stimulation reduced E-cadherin protein level, which could be attenuated by sunitinib. Our recent work reveals that the protein level of snail and the transcriptional activity of smad in sunitinib-treated cells were examined by western-blot and SBE-luciferase assay. Our results imply that sunitinib abolished TGF-β-induced upregulation of snail protein and decreased the transcriptional activity of smad complexes. The western-blot analyses revealed that sunitinib inhibited the upregulation of snail protein level caused by TGF-β treatment. The SBE reporter was constructed by linking the Smad-binding elements promoter upstream of luciferase reporter gene. A remarkable increment of transcriptional activity of Smads complexes was observed in SKOV3 cells exposed to TGF-β, which was significantly prohibited by sunitinib. The current study explores the prohibition of EMT, illustrates the anti-metastatic activities of sunitinib and the underlying mechanisms. [Keywords] Sunitinib; EMT; TGF-β; E-cadherin; Snail; Smad signal pathway Citation Format: Zibo Chen, Lin-lin Chang, Tian-yi Zhou, Dan-dan Wang, Ying Chen, Hong Zhu, Meidan Ying, Bo Yang, Qiao-jun He. Sunitinib suppresses ovarian cancer metastasis through the negative modulation of TGF-β-mediated epithelial-mesenchymal transition. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5079.
High-Resolution Mapping of Postinfarction Reentrant Ventricular Tachycardia
Authors: Elad Anter, Cory M. Tschabrunn, Alfred E. Buxton, Mark E. Josephson
Journal: Circulation (2016)

Background: In vivo description of ventricular tachycardia (VT) circuits is limited by insufficient spatiotemporal resolution. We used a novel high-resolution mapping technology to characterize the electrophysiological properties of the postinfarction reentrant VT circuit. Methods: In 15 swine, myocardial infarction was induced by left anterior descending artery balloon occlusion. Animals were studied 6 to 8 weeks after myocardial infarction. Activation mapping of VTs was performed by using the Rhythmia mapping system. Activation time was based on a combination of bipolar and unipolar electrograms. The response to overdrive pacing from different zones of the circuit was examined. Results: A total of 56 monomorphic VTs were induced (3.8±2.1 per animal). Among these, 21 (37.5%) were hemodynamically stable and allowed mapping of the circuit. Isthmuses were 16.4±7.2 mm long and 7.4±2.8 mm wide. Conduction velocities were slowest at the inward curvature into the isthmus entrance (0.28±0.2 m/s), slightly faster at the outward curvature exit (0.40±0.3 m/s) and nearly normal at the central isthmus (0.62±0.2 m/s). In 3 animals, 2 VT morphologies with opposite axes sharing the same isthmus were mapped. Conduction velocities within the shared isthmus were dependent on the activation vector, consistently slower at the proximal curvature. Overdrive pacing from isthmus sites determined by activation mapping was consistent with entrainment criteria for isthmus. However, dimensions of the isthmus defined by entrainment exceeded dimensions of the isthmus measured by activation mapping by 32±18%. Conclusions: In postinfarction reentrant VT, conduction velocities are slowest at the proximal and distal curvatures. Entrainment mapping overestimates the true size of the isthmus. High-resolution activation mapping of VT may better guide ablation therapy.
Vitamin K1 cream in the management of skin rash during anti-EGFR monoclonal antibody (mAb) treatment in patients with metastatic cancer: First analysis of an observational Italian study.
Authors: C. Pinto, C. Barone, A. Martoni, P. Di Tullio, A. Orlandi, F. Di Fabio, A. Cassano, F. L. Rojas Llimpe, A. Amoroso, S. Pini
Journal: Journal of Clinical Oncology (2011)

594 Background: Cutaneous toxicity, and especially skin rash, is a predictable side- effect of anti-EGFR mAb therapy. Preclinical studies have shown that vitamin K1 reactivated EGFR-mediated signal transduction after inhibition via EGFR receptor antagonists. The aim of this study was to evaluate the impact of vitamin K1 cream in skin rash management. Methods: In two Italian Oncology Centers sequential pts at the first therapy with cetuximab/panitumumab for metastatic cancer were treated with vitamin K1 cream at the first onset of grade ≥2 skin rash. Topical treatment with vitamin K1 (phytomenadione 0.1%) cream twice/die was administered continuously until the end of anti-EGFR treatment. Skin toxicity, according to NCI-CTC v3.0 grading system, was clinically evaluated every week and in a standardized way, taking pictures of 5 different body areas. Treatment benefit was evaluated according to symptom reduction and compliance to therapy. Results: From February to September 2010, 33 pts, 22M (66.6%) and 11F (33.4%), median age 63 years (range 27-79), were evaluated. The primary tumor site was 3 (9.1%) esophagus/stomach, 28 (84.8%) colon-rectum, 2 (6.1%) head-neck. Eighteen (54.5%) pts were treated as first-line and 15 (45.5%) were pretreated. The regimen contained cetuximab in 26 (78.7%) pts and panitumumab in 7 (21.3%). The combination regimens were platinum compounds-based in 23 (69.6%) pts, and irinotecan-based in 6 (18.2%); panitumumab was administered in monotherapy in 4 (12.2%) pts. The median time of vitamin K1 cream treatment was 24 weeks (range 6-28); the oral tetracyclines therapy was associated in 13 (39.4%) pts. The decrease in skin rash to grade 1-0 was observed in 12 (36.4%) pts, and 13 (39.4%) pts showed unchanged grade 2. The increase to grade 3 in skin rash was observed in 8 (24.2%) pts. Good skin rash symptom control was obtained in 69.2% of pts. Cetuximab/panitumumab dose reduction and treatment delays was required in 9 (27.3%) pts. Conclusions: These preliminary results suggest a favorable impact of vitamin K1 cream in skin rash management, which should be considered in a future clinical trial. No significant financial relationships to disclose.
Hands-on Training in the Operating Room as a Method of Continuing Education for Surgeons in Practice
Authors: Paul D. DiMusto, Herbert Chen, K. Craig Kent
Journal: JAMA Surgery (2016)

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Anatomy, Descriptive and Applied.
Authors: F. E. Blaisdell
Journal: JAMA (1913)

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
Loss of SMAD4 Promotes Lung Metastasis of Colorectal Cancer by Accumulation of CCR1+ Tumor-Associated Neutrophils through CCL15-CCR1 Axis
Authors: Takamasa Yamamoto, Kenji Kawada, Yoshiro Itatani, Susumu Inamoto, Ryosuke Okamura, Masayoshi Iwamoto, Ei Miyamoto, Toyofumi F. Chen-Yoshikawa, Hideyo Hirai, Suguru Hasegawa, Hiroshi Date, Makoto M. Taketo, Yoshiharu Sakai
Journal: Clinical Cancer Research (2016)

We have reported loss of SMAD4 promotes expression of CCL15 from colorectal cancer to recruit CCR1+ myeloid cells through the CCL15-CCR1 axis, which contributes to invasion and liver metastasis. However, the molecular mechanism of lung metastasis is yet to be elucidated. Our purpose is to determine whether similar mechanism is involved in the lung metastasis of colorectal cancer.In a mouse model, we examined whether SMAD4 could affect the metastatic activity of colorectal cancer cells to the lung through the CCL15-CCR1 axis. We immunohistochemically analyzed expression of SMAD4, CCL15, and CCR1 with 107 clinical specimens of colorectal cancer lung metastases. We also characterized the CCR1+ myeloid cells using several cell-type-specific markers.In a mouse model, CCL15 secreted from SMAD4-deficient colorectal cancer cells recruited CCR1+ cells, promoting their metastatic activities to the lung. Immunohistochemical analysis of lung metastases from colorectal cancer patients revealed that CCL15 expression was significantly correlated with loss of SMAD4, and that CCL15-positive metastases recruited approximately 1.9 times more numbers of CCR1+ cells than CCL15-negative metastases. Importantly, patients with CCL15-positive metastases showed a significantly shorter relapse-free survival (RFS) than those with CCL15-negative metastases, and multivariate analysis indicated that CCL15 expression was an independent predictor of shorter RFS. Immunofluorescent staining showed that most CCR1+ cells around lung metastases were tumor-associated neutrophil, although a minor fraction was granulocytic myeloid-derived suppressor cell.CCL15-CCR1 axis may be a therapeutic target to prevent colorectal cancer lung metastasis. CCL15 can be a biomarker indicating poor prognosis of colorectal cancer patients with lung metastases. Clin Cancer Res; 23(3); 833-44. ©2016 AACR.
A phase 1b food effect study of the first-in-class, oral, selective inhibitor of nuclear export (SINE) selinexor (KPT-330) in patients (pts) with advanced sarcomas.
Authors: Mrinal M. Gounder, Herbert H. F. Loong, Kjirsten Nyquist-Schultz, Stephanie Baker, Yelena Ustoyev, Lanier R. Tanner, Sharon Shacham, Dilara McCauley, Tami Rashal, Jean-Richard Saint-Martin, Eran Shacham, Sharon Friedlander, Sharon Tamir, Tracey Marshall, Yosef Landesman, Michael Kauffman, Sasha Rebello, Mansoor Raza Mirza, Gary K. Schwartz, Albiruni R. A. Razak
Journal: Journal of Clinical Oncology (2014)

10587 Background: Sarcomas are heterogeneous diseases with multiple genetic abnormalities. XPO1 inhibition can restore the activity of multiple tumor suppressor proteins (TSP) including p53, Rb, and p27; and reduce cyclins and Akt. Selinexor is an oral XPO1 inhibitor that showed potent anti-sarcoma activity in preclinical ASPS, lipo- and bone sarcomas, and preliminary clinical activity in a phase 1 study. Methods: Oral selinexor was given at 30 mg/m2 twice weekly in capsule or tablet form based on an ongoing Phase 1. Appetite stimulants and anti-nausea agents were given. Pharmacokinetic (PK) analyses were performed under fasting and fed states (low vs high fat content). Paired tumor biopsies were obtained. Response evaluation was every 8 weeks (RECIST 1.1). All pts had documented progressive disease (PD) on study entry. Results: 16 evaluable pts (7 M/9 F; median age 55 yrs; median prior regimens: 3; ECOG PS 0/1: 11/6) including 5 leiomyo- (LMS), 4 lipo- (LPS), 3 synovial (SS), and 4 other sarcomas. Grade 3-4 toxicities in cycle 1 included thrombocytopenia without bleeding (12%) and hyponatremia (6%). The most common grade 1/2 AEs in cycle 1 were: nausea (59% G1/6% G2), fatigue (29%/29%), diarrhea (41%/6%), anorexia (18%/6%). PK in 11 patients showed similar exposures (AUC0-inf 3675 vs 3574 ng·hr/mL) of the drug in capsules or tablets; however, food (regardless of fat content) was associated with ~15% increased exposure versus fasted state. Analyses of tumor biopsies during treatment showed that selinexor resulted in nuclear localization of p53 and FOXO1, reduction in XPO1, reduced Ki67 index, increased apoptosis. Response was evaluable in 16 pts: (a) LMS: 3 stable disease (SD, 1 pt with 12% shrinkage), 2 PD; (b) LPS: 4 SD (1 pt with 10% shrinkage); (c) SS 3 PD; (d) chondrosarcoma: 1 SD, 1 PD; (e) chordoma: 1 SD; (f) spindle cell: 1 PD. 9 of the 16 pts remain on study (75-121 days). Conclusions: Selinexor should be taken with food and is generally well tolerated in pts with supportive care. Tumor shrinkage and disease stabilization was observed in a variety of soft tissue sarcomas leading to expansion of the study. Additional studies of selinexor in soft tissue sarcomas are planned. Clinical trial information: NCT01896505.