tbuckley/cabot-search huggingface dataset:
An in vivo genome-wide RNAi screen identifies novel mediators of paclitaxel response in breast cancer
Authors: M. Sultan, B.M. Cruickshank, T. Huynh, E. Lamoureux, D. Vidovic, M.L. Dahn, C. Giacomantonio, M. Langille, P. Marcato
Journal: Annals of Oncology (2019)

Background: Breast cancer treatment often involves the use of paclitaxel to target tumor cells; however, some patients do not respond to treatment and would be better treated with an alternative drug. Thus, being able to identify the genes which when expressed in a tumor predict paclitaxel response prior to administration would improve treatment efficacy and patient survival. Methods: A genome-wide RNAi screen was performed with MDA-MB-231 tumor xenografts in female NOD/SCID mice. This allowed the identification of enriched and depleted shRNA sequences that theoretically target paclitaxel sensitivity and resistance genes, respectively. The screen identified 40 potential novel paclitaxel response genes in breast cancer. Results: We generated individual knockdowns of the top screen-identified sensitivity and resistance genes in MDA-MB-231 cells and orthotopically implanted the knockdowns or control clones in the mammary fat pads of NOD/SCID female mice. The resulting tumor bearing mice were treated systemically with either paclitaxel or phosphate-buffered saline. Paclitaxel inhibited the growth of the MDA-MB-231 control clone tumors but did not significantly affect the growth of the paclitaxel sensitivity knockdown clone tumors. This validates the role of the screen-identified gene as a novel paclitaxel sensitivity mediator. In contrast, knockdown of the screen-identified resistance gene caused more regression in paclitaxel treated mice validating its role as a novel paclitaxel resistance mediator. In vitro mechanism studies revealed that both genes affect paclitaxel treatment outcome through effects on cell cycle progression. Additionally, a gene signature derived from the screen hits achieved 82-85% accuracy in predicting breast cancer patient outcomes to paclitaxel-containing treatment regimens across multiple patient tumor gene expression data sets. Conclusions: A genome-wide RNAi screen has identified novel mediators of paclitaxel response in breast cancer, which also predict patient response to paclitaxel treatment. Additional experiments will enhance the accuracy of the genetic profile and identify breast cancer patients who would most benefit from paclitaxel treatment. Legal entity responsible for the study: Paola Marcato. Funding: CIHR, NSHRF and BHCRI. Disclosure: All authors have declared no conflicts of interest.
Oral low-dose continuous administration of cyclophosphamide and other anticancer agents results in tumor stasis
Authors: Constantine S. A. Markides, Anthony J. Kozielski, Edward R. Petry, Janet A. Early, Dana M. Vardeman, Beppino C. Giovanella
Journal: Cancer Research (2004)

5313  Metronomic chemotherapy, the practice of using low-dose, continuous administration of an anticancer agent to achieve cytotoxic effects in the endothelial cells of a tumor’s growing neovasculature, is still little more than a curiosity in today’s clinical practice. Since the concept was first investigated by Polverini & Novak (1986), most common cancer chemotherapy agents, from all major drug classes, have shown some antiangiogenic activity. Doy (lung), PC3 (prostate), MiaPaCa2 (pancreatic) and HT-29 (colon) cancer cells were subcutaneously xenografted into NIH Swiss nude mice and the tumors allowed to grow to between 250 and 400mm3. Thereafter, water was substituted for a dilute solution designed to administer a continuous low dose of oral drug to each mouse in the cage. When cyclophosphamide, an alkylating agent and a very popular chemotherapeutic drug, was administered at 50 mg/kg/day, it displayed the ability to stabilize tumor size, compared to controls where uncontrolled growth was observed. 5-Fluorouracil used under continuous oral administration had very little observable effect on tumor size when used at either 10 or 20 mg/kg/day. Administration of other chemotherapeutic agents either as metronomic agents or as chemotherapeutics to supplement metronomic therapy is currently under investigation. Using a drug, such as 9-nitrocamptothecin, at therapeutic concentrations in addition to metronomic administration of another drug can be used as a powerful tool to eradicate cancers and to maintain the animals tumor-free thereafter. Polverini PJ, Novak RF. Inhibition of angiogenesis by the antineoplastic agents mitoxantrone and bisantrene. Biochem. Biophys. Res. Commun. 1986; 140: 901-907.
LONG-TERM OUTCOMES OF PATIENTS WITH INDETERMINATE OR POSITIVE LATERAL MARGIN AFTER ENDOSCOPIC RESECTION AND RELATED FACTORS WITH RECURRENCE IN LARGE, SESSILE OR FLAT COLORECTAL POLYPS
Authors: HW Kim, SB Park, DH Kang, CW Choi, SJ Kim, HS Nam, DG Ryu
Journal: Endoscopy (2019)

Recurrence rate in colorectal polyps with indeterminate or positive lateral margin on histology is unclear. We evaluated the long-term outcomes of patients with indeterminate or positive lateral margin after endoscopic resection and related factors with recurrence in large, sessile or flat polyps.
Hepatitis E Virus Infections Among Human Immunodeficiency Virus–Positive Individuals During an Outbreak of Acute Hepatitis A in Taiwan
Authors: Kuan‐Yin Lin, Pi‐Han Lin, Hsin‐Yun Sun, Yi‐Ting Chen, Li‐Hsin Su, Yi‐Ching Su, Shu‐Yuan Ho, Wen‐Chun Liu, Sui‐Yuan Chang, Chien‐Ching Hung, Shan‐Chwen Chang
Journal: Hepatology (2019)

Hepatitis A virus (HAV) and hepatitis E virus (HEV) share the similar fecal-oral transmission route. During an outbreak of sexually transmitted acute hepatitis A among men who have sex with men (MSM) worldwide between 2015 and 2017, we investigated the possibility of sexual transmission and related morbidity of HEV infection among human immunodeficiency virus (HIV)-positive patients. From March 1, 2015 to August 31, 2017, anti-HEV immunoglobulin G was retrospectively determined among 3,293 HIV-positive patients, who were mainly MSM (87.6%) with a median CD4 count of 575 cells/μL. Prevalence and incidence of HEV infection were 3.7% (123 of 3,293) and 4.35 per 1,000 person-years of follow-up (PYFU), respectively, which were significantly lower compared with those of HAV infection (31.1% [996 of 3,204] and 12.61 per 1,000 PYFU, respectively). The number of patients with HEV infection did not increase with the hepatitis A epidemic. The factor associated with prevalent HEV infection was older age (per 1-year increase, adjusted odds ratio, 1.07; 95% confidence interval, 1.05-1.09), but neither sexual orientation nor acquisition of sexually transmitted infections was related to prevalent or incident HEV infection. Among 23 patients with incident HEV infection, 22 patients had viremia caused by HEV genotype 4. No patients had prolonged HEV viremia or clinical symptoms, and only a mild elevation of serum aminotransferase, ranging from 34 to 77 IU/L, was noted. Although 4 patients had hepatitis for a prolonged duration of between 8 and 17 months, no abdominal imaging revealed liver fibrosis or cirrhosis. Conclusion: HEV endemicity remained low among HIV-positive patients in Taiwan during the outbreak of acute hepatitis A. Our data suggest that sexual transmission of HEV with significant morbidity of HEV infection, if any, is rare in this population.
Relationship between tumor infiltrating lymphocytes (TILs) and response to pembrolizumab (pembro)+chemotherapy (CT) as neoadjuvant treatment (NAT) for triple-negative breast cancer (TNBC): Phase Ib KEYNOTE-173 trial
Authors: S. Loi, P. Schmid, G. Aktan, V. Karantza, R. Salgado
Journal: Annals of Oncology (2019)

Background: Higher stromal TILs (sTILs) are associated with higher pathologic complete response (pCR) rates with CT in early-stage TNBC. We evaluated the association between sTILs and PD-L1 expression with response to pembro+CT as NAT for TNBC in KEYNOTE-173 (NCT02622074). Methods: sTILs were quantified pretreatment (PT) and on-treatment (OT; during first 3 weeks of pembro monotherapy). PT PD-L1 expression was reported as combined positive score (CPS). Endpoints were pCR rate (ypT0 ypN0; ypT0/Tis ypN0) and objective response rate (ORR) after the first 4 cycles of NAT (taxane±carboplatin+pembro). Correlation between PD-L1 and sTILs was assessed by Spearman's rank correlation coefficient. Results: Of 60 pts, 53 had tumors evaluated for PT sTILs, 50 for OT sTILs, 52 for PD-L1 CPS, and 51 for both sTILs and CPS. Overall pCR rates were 56.7% (ypT0 ypN0) and 60% (ypT0/Tis ypN0); ORR was 78.3%. There was significant correlation between PT sTILs and PD-L1 CPS (ρ = 0.63; P < 0.001) and between PT sTILs and OT sTILs (ρ = 0.63; P < 0.001). Higher sTILs were significantly associated with response (for PT: ypT0 ypN0 P = 0.033; ypT0/Tis ypN0 P = 0.02; ORR P = 0.028; for OT: ypT0 ypN0 P = 0.01; ypT0/Tis ypN0 P = 0.008; ORR P = 0.005). PT PD-L1 CPS was significantly associated with response: ypT0 ypN0 P = 0.073; ypT0/is ypN0 P = 0.030; and ORR P = 0.021. Responders had higher median PT sTILs vs nonresponders: 40% [7.5, 72.5] vs 10% [5, 27.5] for pCR rate by ypT0 ypN0 and 42.5% [8.8, 71.2] vs 10% [5, 20] for pCR rate by ypT0/Tis ypN0; 20% [5, 70] vs 10% [4, 22.5] for ORR. Responders had higher median OT sTILs vs nonresponders: 65% [11.2, 85] vs 22.5% [4.5,41.2] for pCR rate by ypT0 ypN0 and 65% [5, 86.2] vs 22.5% [3.5, 35] for pCR rate by ypT0/Tis ypN0; 60% [10, 85] vs 10% [1, 30] for ORR. Likelihood ratio tests demonstrated that for both pCR endpoints, PD-L1 CPS (P = 0.936/P=0.492) and PT sTILs (P = 0.746/P=0.715) did not significantly add value to OT sTILs when predicting pCR. Conclusions: Higher quantities of PT sTILs and PD-L1 CPS and OT sTILs were significantly associated with higher pCR rates and ORR in primary TNBC treated with pembro and NAT. Editorial acknowledgement: Rajni Parthasarathy, PhD, and Diane Neer, ELS, MedThink SciCom. Clinical trial identification: NCT02622074. Legal entity responsible for the study: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Funding: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Disclosure: V. Karantza: Emplyee: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, may hold stock/stock options: Merck & Co., Inc., Kenilworth, NJ, USA. R. Salgado: Research support: Roche, Merck. All other authors have declared no conflicts of interest.
Noma (cancrum oris): An unresolved global challenge
Authors: Liviu Feller, Razia A. G. Khammissa, Mario Altini, Johan Lemmer
Journal: Periodontology 2000 (2019)

Abstract Noma (canrum oris) is a mutilating necrotizing disease of uncertain etiology, but it is accepted that it is caused primarily by a polybacterial infection with secondary ischemia. The consequent necrotizing fasciitis, myonecrosis, and osteonecrosis results in destruction of facial structures with severe functional impairment and disfigurement. It most frequently affects children, particularly in sub‐Saharan Africa, who are malnourished or debilitated by systemic conditions including but not limited to malaria, measles, and tuberculosis; and less frequently debilitated HIV ‐seropositive subjects. In the vast majority of cases, in susceptible subjects, noma is preceded by necrotizing stomatitis. However, it has been reported, albeit rarely, that noma can arise without any preceding oral lesions being observed. Noma is not recurrent and is not transmissible.
ENDOSCOPIC MANAGEMENT OF AN INTRAPARIETAL OESOPHAGEAL HEMATOMA, SECONDARY COMPLICATION OF POEM IN A TYPE 1 ACHALASIA, PREVIOUSLY TREATED BY HELLER MYOTOMY
Authors: J Rivory, L Alexandru, F Rostain, T Ponchon, B Oung, J Jacques, S Roman, F Mion, M Pioche
Journal: Endoscopy (2019)

Achalasia is an idiopathic condition characterized by abnormally elevated pressure of the lower oesophageal sphincter (LES) and abnormal oesophageal peristalsis. Before per oral endoscopic myotomy (POEM) the treatment was either by drugs (nitrates, calcium blockers), endoscopic pneumatic dilatation or by surgical myotomy.
PREDICTING ADVERSE CLINICAL OUTCOMES FOR COLORECTAL ENDOSCOPIC SUBMUCOSAL DISSECTION (CR-ESD): SMSA VERSUS A NEW EXPERIENCE-LESION SCORE. A MULTICENTER SPANISH PROSPECTIVE STUDY
Authors: JC Marín-Gabriel, A Herreros de Tejada Echanojauregui, F Múgica-Aguinaga, F Ramos-Zabala, E Albéniz-Arbizu, PJ Rosón-Rodríguez, J de la Peña-García, Á Terán-Lantarón, J Rodríguez-Sánchez, D García-Romero, A Amorós-Tenorio, A Sánchez-Yagüe, H Uchima, AJ del Pozo-García, C Dolz-Abadía, MG Fernández-Esparrach, J Santiago-García, Ó Nogales-Rincón, A Álvarez-Delgado, H Cortes-Pérez, R Durán-Bermejo
Journal: Endoscopy (2019)

To develop a new preoperative model to improve the ability of the SMSA score to predict adverse clinical outcomes of CR-ESD: duration of the procedure > 240 min., piecemeal resections, aborted procedures and complications (intraprocedural and delayed perforations and delayed bleedings).
Clinical, biological and histological features predictive of response to everolimus in metastatic breast cancer patients
Authors: V. Van den bossche, G. Jadot, D. Augusto, V. Samartzi, S. Castela, S. Lejeune, E. Seront
Journal: Annals of Oncology (2019)

Background: The PI3K/Akt/mTOR pathway is frequently activated in breast cancer (BC) and is implicated in resistance to endocrine therapy (ET). Addition of everolimus (EVE), an mTOR inhibitor, to ET improves cancer control compared to ET alone. However, in previous studies, the median progression-free survival (PFS) did not exceed 7 months (mo), responses were inconsistent and there was no efficient predictive biomarker of efficacy. We aimed to define a correlation between clinical, biological or histological features and EVE efficacy. Methods: Retrospective analysis of metastatic breast cancer (mBC) patients treated with EVE in our centers between 2013 and 2018. Clinical characteristics (type of metastases), biological features (albumin levels, lactate dehydrogenase (LDH) and neutrophil/lymphocyte ratio (NLR)) and tumors features (estrogen or progesterone receptors, KI67, grade) were analyzed. In available tissue samples collected before EVE initiation, immunohistochemistry (IHC) for PTEN, cMET and pS6RP was performed. All these features were correlated with PFS. Results: There were 61 women, median age 59 yo, with mBC treated with EVE, and 35 tumor samples were available. Median PFS was 6,5 mo (1-32 mo). 3 tumor-related features were associated with poor prognosis (LDH >230 U/L, high NLR (>3) and visceral metastases). A score was made out of these 3 criteria : patients with a "high score" (HS) (2 or 3 criteria) had a low PFS compared to "low score" (LS) patients (0-1 criteria) (4 vs 11 mo, respectively; p < 0,001). Patients with IHC c-MET+ had a lower PFS in LS (4 vs 13,5 mo, p = 0,01) and HS patients (c-MET- PFS 8,5 mo vs 3 mo if c-MET+, p = 0,02). For HS patients with PTEN loss also had a shorter PFS (3 vs 5 mo, p = 0,003). Combining these criteria, PFS in LS PTEN-/cMET- was 10,5 mo and only 3 mo in HS PTEN+/cMET + (p < 0,001). Conclusions: Visceral metastases, high NLR and high LDH were associated with lower PFS on EVE. They are useful, quick and economic scores to predict EVE efficacy in mBC patients. Additional histological characteristics such as PTEN and c-MET could help determine, within this population of patients, the ones who will and the ones who will not benefit from EVE treatment. Legal entity responsible for the study: Emmanuel Seront - Hôpital de Jolimont. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
ENDOSCOPIC MANAGEMENT OF DIFFICULT BENIGN BILIARY AND PANCREATIC STRICTURES USING A WIRE-GUIDED CYSTOTOME
Authors: C Mangas-Sanjuan, M Bozhychko, L Compañy, FA Ruiz, J Martínez Sempere, JA Casellas, J Ramón Aparicio
Journal: Endoscopy (2019)

Endoscopic management using standard accessories is the preferred modality for treating benign biliary/pancreatic strictures. However, if there're difficult and severe strictures, the passage of accessories over a guidewire across the stricture isn't feasible. Hence, our aim is to report our experience regarding the use of a standard diathermic dilator (cystotome) to aid in stricture dilation and stent placement in patients with difficult strictures.
Characterization of the Subventricular-Thalamo-Cortical Circuit in the NP-C Mouse Brain, and New Insights Regarding Treatment
Authors: Min Hee Park, Byung Jo Choi, Min Seock Jeong, Ju Youn Lee, In Kyung Jung, Kang Ho Park, Hye Won Lee, Tomoyuki Yamaguchi, Hugo H. Marti, Beom Hee Lee, Edward H. Schuchman, Hee Kyung Jin, Jae-sung Bae
Journal: Molecular Therapy (2019)
COLD SNARE POLYPECTOMY VS HOT SNARE POLYPECTOMY VS ARGON PLASMA COAGULATION (APC) FOR 5 – 9MM LEFT-SIDED COLORECTAL POLYPS: A PROSPECTIVE RANDOMIZED TRIAL
Authors: L Varytimiadis, N Viazis, V Papastergiou, G Kyriakopoulos, T Argyrakos, C Pontas, I Papanikolaou, N Arkadopoulos, V Smirniotis, G Mantzaris
Journal: Endoscopy (2019)

The optimal technique for the removal of small colorectal polys is debatable. We aimed to compare the recurrence rates among three endoscopic treatment modalities for 5 – 9 mm left-sided colorectal polyps.
The Hospital Readmissions Reduction Program — Time for a Reboot
Authors: Rishi K. Wadhera, Robert W. Yeh, Karen E. Joynt Maddox
Journal: New England Journal of Medicine (2019)

Some policymakers have pushed for the HRRP to be expanded to cover all conditions treated in inpatient settings. Others, including many clinicians and researchers, have expressed skepticism regarding the program’s effects and concerns about unintended consequences.
Diffuse Hyperpigmentation in a Patient With an Axillary Mass
Authors: Shruti Bhandari, Prashant Tripathi, Hamza Hashmi
Journal: JAMA Oncology (2019)

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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Oncology journal
PERORAL ENDOSCOPIC SEPTOTOMY (POES) FOR ZENKER DIVERTICULUM: A PILOT STUDY
Authors: A Repici, R Maselli, PJ Belletrutti, PA Galtieri, A Fugazza, A Anderloni, E Chiara Ferrara, S Carrara, M Di Leo, M Spadaccini, F D'Amico, L Lamonaca, V Craviotto, A Capogreco, A Dal Buono, M Colombo, R Gabbiadini, A Sethi, C Castoro, C Hassan
Journal: Endoscopy (2019)

Treatments Zenker's diverticulum (ZD) aim to dissect the muscle in order to remove the underlying dysfunctional condition. In the last decade, the endoscopic septotomy performed with a flexible endoscope has been reported as a safe and effective alternative to both open surgery and rigid endoscopic diverticulotomy. More recently, Li described a novel endoscopic technique, called Z-POEM, inspired by the per-oral endoscopic myotomy (POEM) developed for Achalasia. Patients with short septum diverticulum represent a difficult-to-be-treated subgroup of patients because of anatomical limitation leading to reduced operation space. Aim of this study was to investigate the efficacy and safety of a novel alternative third space approach, called Per-Oral Endoscopic Septotomy (POES) to treat symptomatic patients with short-septumZD.
Laterality and Stimulation Bias in Meta-analysis of Placebo Responses—Reply
Authors: Matthias Zunhammer, Ulrike Bingel, Tor D. Wager
Journal: JAMA Neurology (2019)

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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Neurology journal
DIRECT PERORAL CHOLANGIOSCOPY FOR DIFFICULT BILIARY STONES TREATMENT DIRECT PERORAL CHOLANGIOSCOPY IN DIFFICULT BILIARY STONES
Authors: M Silva, S Gomes, E Rodrigues-Pinto, AL Santos, A Peixoto, P Pereira, G Macedo
Journal: Endoscopy (2019)

Peroral cholangioscopy (POC) using a conventional endoscope allows better visualization of the biliary tree and the use of devices that are not possible with the duodenoscope and is a useful technique for the treatment of difficult biliary lithiasis' cases. The authors describe one of these cases, resolved using POC and polypectomy snare.