tbuckley/cabot-search huggingface dataset:
ALCAM contributes to brain metastasis formation in non-small-cell lung cancer through interaction with the vascular endothelium
Authors: Justine Münsterberg, Desirée Loreth, Laura Brylka, Stefan Werner, Jana Karbanova, Monja Gandrass, Svenja Schneegans, Katharina Besler, Fabienne Hamester, José Ramon Robador, Alexander Thomas Bauer, Stefan Werner Schneider, Michaela Wrage, Katrin Lamszus, Jakob Matschke, Yogesh Vashist, Güntac Uzunoglu, Stefan Steurer, Andrea Kristina Horst, Leticia Oliveira-Ferrer, Markus Glatzel, Thorsten Schinke, Denis Corbeil, Klaus Pantel, Cecile Maire, Harriet Wikman
Journal: Neuro-Oncology (2020)

Abstract Background Brain metastasis (BM) in non-small-cell lung cancer (NSCLC) has a very poor prognosis. Recent studies have demonstrated the importance of cell adhesion molecules in tumor metastasis. The aim of our study was to investigate the role of activated leukocyte cell adhesion molecule (ALCAM) in BM formation in NSCLC. Methods Immunohistochemical analysis was performed on 143 NSCLC primary tumors and BM. A correlation between clinicopathological parameters and survival was developed. Biological properties of ALCAM were assessed in vitro by gene ablation using CRISPR/Cas9 technology in the NCI-H460 NSCLC cell line and in vivo by intracranial and intracardial cell injection of NCI-H460 cells in NMRI-Foxn1nu/nu mice. Results ALCAM expression was significantly upregulated in NSCLC brain metastasis (P = 0.023) with a de novo expression of ALCAM in 31.2% of BM. Moderate/strong ALCAM expression in both primary NSCLC and brain metastasis was associated with shortened survival. Functional analysis of an ALCAM knock-out (KO) cell line showed a significantly decreased cell adhesion capacity to human brain endothelial cells by 38% (P = 0.045). In vivo studies showed significantly lower tumor cell dissemination in mice injected with ALCAM-KO cells in both mouse models, and both the number and size of BM were significantly diminished in ALCAM depleted tumors. Conclusions Our findings suggest that elevated levels of ALCAM expression promote BM formation in NSCLC through increased tumor cell dissemination and interaction with the brain endothelial cells. Therefore, ALCAM could be targeted to reduce the occurrence of BM. Key Points 1. ALCAM expression associates with poor prognosis and brain metastasis in NSCLC. 2. ALCAM mediates interaction of NSCLC tumor cells with brain vascular endothelium. 3. ALCAM might represent a novel preventive target to reduce the occurrence of BM in NSCLC.
A Randomized Controlled Trial of a 6-Month Low-Carbohydrate Intervention on Disease Progression in Men with Recurrent Prostate Cancer: Carbohydrate and Prostate Study 2 (CAPS2)
Authors: Stephen J. Freedland, Jenifer Allen, Aubrey Jarman, Taofik Oyekunle, Andrew J. Armstrong, Judd W. Moul, Howard M. Sandler, Edwin Posadas, Dana Levin, Emily Wiggins, Lauren E. Howard, Yuan Wu, Pao-Hwa Lin
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Both weight loss and low-carbohydrate diets (LCD) without weight loss prolong survival in prostate cancer models. Few human trials have tested weight loss or LCD on prostate cancer. Experimental Design: We conducted a multi-site randomized 6-month trial of LCD versus control on PSA doubling time (PSADT) in patients with prostate cancer with biochemical recurrence (BCR) after local treatment. Eligibility included body mass index (BMI) ≥ 24 kg/m2 and PSADT 3 to 36 months. The LCD arm was instructed to eat \le $20 g/carbs/day; the control arm instructed to avoid dietary changes. Primary outcome was PSADT. Secondary outcomes included weight, lipids, glucose metabolism, and diet. Results: Of 60 planned patients, the study stopped early after an interim analysis showed futility. Twenty-six LCD and 19 control patients completed the study. At 6 months, although both arms consumed similar protein and fats, the LCD arm reduced carbohydrates intake (−117 vs. 6 g, P &amp;lt; 0.001) and lost weight (−12.3 vs. −0.60 kg, P &amp;lt; 0.001). The LCD arm increased HDL and reduced triglycerides and HbA1c with no difference in total cholesterol or glucose. Mean PSADT was similar between LCD (22 months) and control (15 months, P = 0.313) arms. In a post hoc exploratory analysis accounting for prestudy PSADT, baseline PSA, primary treatment, and hemoconcentration, PSADT was significantly longer in LCD versus control (30 vs. 13 months, P = 0.007) arms. Adverse events were few, usually mild, and returned to baseline by 6 months. Conclusions: Among BCR patients, LCD induced weight loss and metabolic benefits with acceptable safety without affecting PSADT, suggesting LCD does not adversely affect prostate cancer growth and is safe. Given exploratory findings of longer PSADT, larger studies testing LCD on disease progression are warranted.
Gender and quality of life in bladder cancer.
Authors: Kathryn Gessner, Sean McCabe, Pauline Filippou, Hannah McCloskey, Judy Hamad, Allison Mary Deal, John L. Gore, Angela Smith
Journal: Journal of Clinical Oncology (2020)

464 Background: Quality of life among cancer survivors has been shown to vary by gender. Our objective was to evaluate differences in generic and bladder cancer-specific quality of life (QOL) based on gender among a large bladder cancer cohort. Methods: We performed a cross-sectional survey of bladder cancer patients using the Bladder Cancer Advocacy Network Patient Survey Network and Inspire platforms to determine generic and bladder cancer-specific QOL using the EORTC QLQ-C30 and Bladder Cancer Index. Patients were also queried regarding demographic, socioeconomic and clinical characteristics. The survey was advertised. We present descriptive statistics and a multiple linear regression model to identify factors independently associated with QOL domain score. Results: 972 respondents self-identified as patients with bladder cancer. Among respondents, 41% were female and 97% were white. The mean age was 67.6 years (range 29 to 93 years). Respondents were highly educated (67% completed college). 63% of patients identified as having non-invasive (NMIBC) cancer (n=578), 30% had MIBC (n=270), and 7% had metastatic bladder cancer (n=63). On multivariable analysis ( Table), female gender was significantly associated with worse generic QOL (p&lt;0.001), bowel function (p=0.001), and sexual function (p=0.02), and women trended toward worse urinary function (p=0.06), controlling for age, race, stage, comorbidity and years since diagnosis. Conclusions: Lower generic and domain-specific QOL scores are more common among female bladder cancer patients. Differential impact by gender may be important for the development of tailored interventions to improve QOL for bladder cancer patients. [Table: see text]
Overall survival and independent review of response in CheckMate 214 with 42-month follow-up: First-line nivolumab + ipilimumab (N+I) versus sunitinib (S) in patients (pts) with advanced renal cell carcinoma (aRCC).
Authors: Nizar M. Tannir, David F. McDermott, Bernard Escudier, Hans J. Hammers, Osvaldo Rudy Aren, Elizabeth R. Plimack, Philippe Barthelemy, Victoria Neiman, Saby George, Camillo Porta, Thomas Powles, Frede Donskov, Marc-Oliver Grimm, Asim Amin, Scott S. Tykodi, Yoshihiko Tomita, Brian I. Rini, M. Brent McHenry, Shruti Shally Saggi, Robert J. Motzer
Journal: Journal of Clinical Oncology (2020)

609 Background: N+I demonstrated superior OS and ORR v S in intention-to-treat (ITT) and intermediate/poor-risk (IP) pts with aRCC in CheckMate 214. Here, we report OS, response outcomes per independent radiology review committee (IRRC), and safety with extended min follow-up of 42 mo. Methods: Pts with clear cell aRCC were randomized 1:1 to N 3 mg/kg + I 1 mg/kg Q3W×4 and then N 3 mg/kg Q2W, or S 50 mg daily for 4 wk on, 2 wk off. Endpoints were OS, ORR, and PFS per IRRC using RECIST v1.1 in IP (primary), ITT (secondary), and favorable pts (FAV; exploratory). Results: OS remained superior in ITT (HR 0.72) and IP (HR 0.66) pts with N+I v S (Table). ORR per IRRC was higher and more responses were ongoing with N+I v S (68% v 53% [ITT] and 68% v 52% [IP]). More pts achieved complete response (CR) with N+I and these were ongoing in 86% [ITT] and 84% [IP] of pts. The PFS probability with N+I stabilized after 24 mo at ~35% in ITT and IP pts, whereas probabilities declined over time with S. Among FAV pts, while ORR was 29% with N+I v 54% with S, more pts achieved CR (13% v 6%), and more responses were ongoing (69% v 54%) with N+I v S; 94% of CRs in FAV pts were ongoing with N+I. OS benefits were similar in both arms and PFS probabilities are stabilizing with N+I and declining with S in FAV pts. The incidence of any and grade 3–4 treatment-related AEs was consistent with previous reports and no new drug-related deaths occurred in either arm. Response outcomes per investigator will also be reported. Conclusions: Superior OS and ORR with N+I v S was maintained in ITT and IP pts. More pts treated with N+I experienced CR compared with S, responses and CRs were durable, and PFS probabilities stabilized with N+I after extended follow-up. No new safety signals emerged. Clinical trial information: NCT02231749 .[Table: see text]
The gender impacts on Airway hyperresponsiveness in asthmatic adolescents
Authors: Chikako Motomura, Takeshi Oki, Masatoshi Wakatsuki, Toshiaki Kawano, Koki Okabe, Takehito Fukushima, Daisuke Yasunari, Hiroshi Matsuzaki, Mihoko Iwata, Youko Murakami, Naohiko Taba, Satoshi Honjo, Hiroshi Odajima
Journal: Journal of Allergy and Clinical Immunology (2020)
Multicenter comparison of outcomes for clinical and pathologic T3a renal cell carcinoma.
Authors: Aaron Bradshaw, Fady Ghali, Nathan Miller, Cathrine Keiner, Raksha Dutt, Margaret Meagher, Kendrick Yim, Devin Patel, Robert Guy Uzzo, Brian R. Lane, Umberto Capitanio, Ithaar Derweesh
Journal: Journal of Clinical Oncology (2020)

758 Background: The identification of venous thrombus in patients with renal cell carcinoma (RCC) is particularly challenging, with a substantial number upstaged to pathologic T3a following intervention. We compared survival outcomes between patients with initial cT3a status versus those upstaged to pT3a. Methods: This is a retrospective, multicenter analysis of patients with cT3a or pT3a RCC who underwent operative management. Primary outcome was recurrence-free survival (RFS). Secondary outcomes were overall survival (OS) and cancer-specific survival (CSS). Cox regression multivariable analysis (MVA) was utilized for primary outcome. Kaplan-Meier analyses (KMA) were conducted to describe RFS, OS, and CSS with log-rank test comparing clinical and upstaged pathologic T3a groups. Results: 770 patients were analyzed (cT3a 184, pT3a 586, median follow-up 28 months). Average pathologic tumor size was smaller in pT3a (7.2 cm vs 8.7 cm, p &lt; 0.01), with no significant differences in clinical variables. A similar proportion underwent radical nephrectomy (vs. partial) (89.7% cT3a and 85.0% pT3a, p = 0.11) with no significant different in positive margin rate (3.8% cT3a, 4.8% pT3a, p = 0.23). However, a higher proportion of patients with cT3a disease were pathologically node positive (19.0% vs. 10.8%, p &lt; 0.01) and demonstrated a higher rate of recurrence (cT3a 51.1% vs. pT3a 34.1%, p &lt; 0.01) despite shorter mean follow-up (cT3a 33.0 vs. pT3a 50.7 mo, p &lt; 0.01). MVA for RFS revealed cT3a staging (pT3a referent, HR 1.72, p &lt; 0.01), positive margins (HR 2.85, p &lt; 0.01), and clear cell histology (HR 1.68, p &lt; 0.01) to be independently associated with higher recurrence rate, while partial nephrectomy (radical referent, HR 0.259, p &lt; 0.01) was associated with a decreased rate. KMA revealed 5-year RFS of 34.4% and 60.6% for cT3a and pT3a respectively (p &lt; 0.01). KMA for secondary outcomes revealed 5-year OS rates of 56.7% and 62.0% (p = 0.02) and 5-year CSS of 74.4% and 67.7% for cT3a and pT3a respectively (p = 0.01). Conclusions: Patients with cT3a RCC have poorer oncologic outcomes than those with upstaged pT3a RCC. Suspected venous involvement on pre-operative imaging may indicate more aggressive or advanced disease than that found during surgery.
Biochemical relapse in very high-risk prostate cancer after radical prostatectomy and DC-vaccine loaded with tumor RNA, hTERT, and survivin.
Authors: Wolfgang Lilleby, Anne Merete Tryggestad, Iris Bigalke, Bjørn Brennhovd, Karol Axcrona, Dag Josefsen, Ulrika Axcrona, Gunnar Kvalheim, Svein Dueland
Journal: Journal of Clinical Oncology (2020)

324 Background: Patients with very high-risk prostate cancer (VHR-PC) features experience worse outcome after radical prostatectomy. This study was designed to assess biochemical failure and toxicity of adjuvant dendritic cells vaccine (DCV) in prostate cancer patients who are at greatest risk for cancer progression. Methods: Twenty patients with pathological stage pT2 - pT3b and Gleason score 7B-10, pN0, pN+ or pNx were enrolled into the approved study DC-005. The primary end point was clinical failure. Ten patients were tested for disseminated tumor cells (DTCs) to the bone marrow before inclusion to the study. Three patients out of 10 patients had positive DTCs detection in bone marrow. The mean age of the cohort was 63 years (SD 6.9 years), and three patients had postsurgical pN1 status. Eighteen patients had two or more high-risk factors (ISUP grade 5, T3- stage and or PSA &gt; 20 ng/mL). Autologous dendritic cells were transfected with mRNA for hTERT, survivin and tumor mRNA. The DCV product was applied intradermally after curative intended surgery once per week the first months, then once per months the first year, thereafter every 3 months for two years or until biochemical progression (PSA relapse cut-off ≥ 0.3). Results: After 5 years follow-up (FU) 62% (12/20 patients) had not biochemically progressed and with a median FU of 69 months all patients included in the study are alive. Five patients were treated with salvage and one patient with adjuvant radiation treatment, three patients received limited ADT, and three patients are on first line ADT, none of those eight patients have experienced castration resistant prostate cancer. The toxicity was mild with no serious adverse event related to DCV. Conclusions: Adjuvant DCV mitigates the time to biochemical progression. These results appear favorably compared to historical controls in VHR-PC. The clinical outcomes of this study warrants a future enlarged clinical trial. Clinical trial information: NCT01197625.
A novel mutation in <i>MUTYH</i>-associated polyposis (MAP) syndrome
Authors: F. Fostira, C. Panopoulos, K. Papademitriou, G. Lypas, G. Lypas, V. Barbounis, A. Efremidis, D. Yannoukakos
Journal: Journal of Clinical Oncology (2009)

e15022 Background: MUTYH-associated polyposis (MAP) syndrome is inherited as a recessive trait and is characterized by the intrinsic phenotypic feature of adenomas present at the individual's colorectum. In the case of non-surgical removal of these polyps, adenoma will transform to carcinoma. Colorectal tumours from mutation carriers display an excess of somatic mutations, specifically G:C to T:A transversions. The risk of colorectal cancer among biallelic mutations carriers seems to be close to 100% by the age of 60. Methods: Four families meeting the MAP phenotypic criteria were studied.Genomic DNA was purified from peripheral blood leukocytes following standard chloroform extraction. The complete coding sequences of the MUTYH-gene, including splice junctions, were amplified by Polymerase Chain Reaction (PCR) and electrophorized in an ABI Prism 310 Genetic Analyzer. Results: Analysis of the MUTYH gene revealed five different germline mutations, one of which novel and never characterized in respects of its pathogenicity. A mutation has been identified on exon 7 of the MUTYH gene at a homozygous state, in an individual with less than one hundred colorectal polyps at the age of forty. Another patient diagnosed with colorectal cancer at the age of 34 carried two maternally and one paternally inherited mutation, located on exon 14. A milder MAP phenotype characterized an individual, who was diagnosed with less than one hundred polyps at the age of 69. Genetic testing revealed that the patient was compound heterozygote for two missense variants located on exons 8 and 12 of the MUTYH gene. Conclusions: A novel mutation located on intron 6 of the MUTYH gene has been identified in two families. Our findings confirm previous observations highlighting the necessity for genetic testing of MUTYH in patients with MAP phenotypic features, as well as his/her extended family, in order to determine the phenotyping expression of each mutation and propose the appropriate clinical surveillance, which includes biennial colonoscopy after the age of 30. In specialized cases surgical intervention might be essential. No significant financial relationships to disclose.
Resting-state fMRI detects alterations in whole brain connectivity related to tumor biology in glioma patients
Authors: Veit M Stoecklein, Sophia Stoecklein, Franziska Galiè, Jianxun Ren, Michael Schmutzer, Marcus Unterrainer, Nathalie L Albert, Friedrich-W Kreth, Niklas Thon, Thomas Liebig, Birgit Ertl-Wagner, Joerg-C Tonn, Hesheng Liu
Journal: Neuro-Oncology (2020)

Abstract Background Systemic infiltration of the brain by tumor cells is a hallmark of glioma pathogenesis which may cause disturbances in functional connectivity. We hypothesized that aggressive high-grade tumors cause more damage to functional connectivity than low-grade tumors. Methods We designed an imaging tool based on resting-state functional (f)MRI to individually quantify abnormality of functional connectivity and tested it in a prospective cohort of patients with newly diagnosed glioma. Results Thirty-four patients were analyzed (World Health Organization [WHO] grade II, n = 13; grade III, n = 6; grade IV, n = 15; mean age, 48.7 y). Connectivity abnormality could be observed not only in the lesioned brain area but also in the contralateral hemisphere with a close correlation between connectivity abnormality and aggressiveness of the tumor as indicated by WHO grade. Isocitrate dehydrogenase 1 (IDH1) mutation status was also associated with abnormal connectivity, with more alterations in IDH1 wildtype tumors independent of tumor size. Finally, deficits in neuropsychological performance were correlated with connectivity abnormality. Conclusion Here, we suggested an individually applicable resting-state fMRI marker in glioma patients. Analysis of the functional connectome using this marker revealed that abnormalities of functional connectivity could be detected not only adjacent to the visible lesion but also in distant brain tissue, even in the contralesional hemisphere. These changes were associated with tumor biology and cognitive function. The ability of our novel method to capture tumor effects in nonlesional brain suggests a potential clinical value for both individualizing and monitoring glioma therapy.
Differential expression of PSMA and 18F-fluciclovine transporter genes in metastatic castrate-resistant and treatment-emergent small cell/neuroendocrine prostate cancer.
Authors: Carissa Chu, Mohammed Alshalalfa, Martin Sjöström, Shuang Zhao, Annika Herlemann, Jonathan Chou, Avi Lefridge Baskin, Brandon Arvin Virgil Mahal, Daniel Eidelberg Spratt, Matthew R. Cooperberg, Eric Jay Small, Rahul Raj Aggarwal, Anthony C. Wong, Sima P. Porten, Thomas Hope, Paul L. Nguyen, Edward M. Schaeffer, Peter Carroll, Felix Y Feng
Journal: Journal of Clinical Oncology (2020)

24 Background: 18 F-fluciclovine (Axumin) PET/CT imaging is recommended by the NCCN in the setting of biochemical recurrence, while prostate-specific membrane antigen (PSMA) PET/CT is preferred by the EAU. The utility of these methods in the post-androgen deprivation therapy (ADT) setting however, is less defined. Our objective was to compare relative gene expression of the molecular targets of these imaging modalities— fluciclovine transporter genes (LAT1-4, ASCT1-2) and PSMA—in metastatic castrate resistant prostate cancer (mCRPC) and treatment-emergent small cell/neuroendocrine prostate cancer (t-SCNC). Methods: Genome-wide expression profiles of five mCRPC cohorts (Aggarwal, Grasso, Kumar, Beltran, Robinson, et al) were used to characterize relative expression of fluciclovine transporter (LAT1-4, ASC1-2) and PSMA (FOLH1) genes. 3 cohorts (Kumar, Beltran, Aggarwal) were enriched with t-SCNC tumors. The GSE35988 cohort included primary tumors and mCRPC. RNA expression profiling methods were consistent within cohorts. Results: 518 mCRPC specimens were included. In the GSE35988 cohort, PSMA expression was downregulated in mCRPC when compared to primary localized tumors (p=0.01). PSMA expression was further depressed in t-SCNC when compared with mCRPC (p&lt;0.001). Of the fluciclovine transporter genes, LAT1 and LAT4 were overexpressed in mCRPC when compared to primary tumors, while ASC2 was less expressed (p&lt;0.001). LAT1 was further overexpressed in t-SCNC when compared to mCRPC, while LAT2 was less expressed (p&lt;0.001). PSMA expression was negatively correlated with LAT1 (p&lt;0.001) but positively correlated with LAT2 (p=0.006). Other fluciclovine transporters were not correlated. Conclusions: Expression of PSMA and a subset of fluciclovine transporter genes are inversely correlated in mCRPC and t-SCNC. These findings suggest that fluciclovine-based imaging may play a role in castrate resistant states. Clinical comparison between PSMA- and fluciclovine-based imaging modalities in mCRPC and t-SCNC is warranted.
Release of immigration detainees: RECONNECTed yet not protected from harm of detention
Authors: Mary Kamara
Journal: BMJ (2020)

Nearly two thirds of those held in immigration removal centres (IRCs) are released into the community1 and I would like to thank Arnold and colleagues for raising awareness of the serious obstacles to accessing ongoing care following release.2

The authors note that new service specifications for primary care in IRCs will be introduced in 2020. Medical Justice, the only …
Efficacy of Probiotics Administration in Patients with Partly Controlled Asthma: A Randomized Placebo Controlled Trial
Authors: Sasipa Sangkanjanavanich, Chirawat Chiewchalermsri, Atik Sangasapaviliya, Wat Mitthamsiri, Panitan Pradubpongsa, Tadech Boonpiyathad
Journal: Journal of Allergy and Clinical Immunology (2020)