bluuebunny/crossref_metadata_2025_split huggingface dataset:
Limb length in bariatric surgery of Roux-en-Y gastric bypass (RYGB): An integrative review
Authors: Landal Cavassin Bruno , Cabral Brandalizze Carolina 
Published: July 2021

Introduction: Roux-en-Y gastric bypass is considered the gold standard surgical technique for obesity. The variation in limb length may be related to metabolic improvement and nutritional deficiencies. However, the ideal measurement still a controversial subject in the literature. This study aims to perform an integrative literature review and associate the optimal limb length, considering the maximum weight loss with the minimum nutritional complications. Methods: Integrative literature review conducted using electronic searches (1992 - 2020) in databases MEDLINE/Pubmed and BVS (Biblioteca Virtual da Saúde)/LILACS, through the terms "(bariatric surgery) AND (limb length)". A total of 340 articles were found, 26 articles were included in this review. Results: Current evidence supports using shorter limb lengths in patients with BMI < 50 kg/m2, and longer limbs in patients with severe type 2 diabetes mellitus and/or dyslipidemia or superobese patients (BMI >= 50 kg/m2), considering the benefits in comorbidities resolution. A shorter common limb increases the incidence of nutritional disorders. There is a wide variation in jejunoileal length among patients. Conclusion: Measuring the intraoperative jejunoileal length and individualizing the surgery may bring benefits in weight loss, comorbidities resolution, and reduce the incidence of nutritional disorders. However, more randomized controlled trials are needed on this topic.
Avances y desafíos en las vacunas el para control de la pandemia por COVID-19
Authors: Weinstein Caroline , Andresen Max , Corrales Raúl , Gallardo Jorge , Noriega Viviana , Sánchez Eliana 
Published: July 2021

Desde diciembre de 2020 a la fecha se ha observado un notable avance en la diversidad de vacunas para combatir la COVID-19 que han recibido la aprobación para uso de emergencia en Chile y en el mundo. Nunca en la historia se ha ofrecido tal variedad de plataformas para una misma enfermedad infecciosa, demostrando que el desastre pandémico pudo empujar el avance de desarrollos científico-tecnológicos que se encontraban ad-portas de alcanzar el mercado farmacéutico. Es así como a la fecha, en Chile, han recibido aprobación para uso de emergencia, vacunas basadas en la estrategia convencional constituida por virus completo inactivado (Coronavac de Sinovac), en vectores adenovirales que codifican para la proteína S (ChAdOx1 nCOVID-1 de Astrazeneca, Convidencia de Cansino y Jansen de Johnson y Johnson) y nanopartículas lipídicas que transportan el mRNA que codifica para la misma proteína S (BNT162b mRNA de Pfizer/Biontech)(Chung et al., 2021).
A Rare Cancer Opportunity
Authors: Lacey James V. 
Published: July 2021

Abstract
In this issue of Cancer Epidemiology, Biomarkers & Prevention, Gallicchio and colleagues analyze recent rare-cancers research and suggest broad themes for accelerating progress in this important area. Whether the type of portfolio creation and portfolio management strategies that have worked for common cancers also work best for rare cancers warrants asking. This commentary argues for consideration of additional approaches. Incorporating principles and successes from large-scale network-based clinical trials and from advocacy-based research, and new ways to approach consortia, might accelerate the quantity and improve the quality of future rare-cancer research. Rare cancers significantly influence the overall cancer burden and cancer disparities. Creative community-based approaches to improve rare-cancers research should be considered.
See related article by Gallichio et al., p. 1305
The 9th Symposium on Global Cancer Research: Looking Back and Charting a Path Forward in Global Cancer Control
Authors: Duncan Kalina , Allen Carl E. , Anandasabapathy Sharmila , Baker Ellen , Bourlon María T. , Eldridge Linsey , Garton Elise M. , Ghosh Shubhra , Hatcher Rashieda J. , Hidalgo Catherine , Lorenzoni Cesaltina , Martin Keith , Mutebi Miriam , Cobb Dalal Najjar , Newman Lisa A. , Paz-Soldan Valerie A. , Pearlman Paul C. , Prakash Laura , Rositch Anne F. , Smith Jenna , Varon Melissa Lopez , Cira Mishka K. 
Published: July 2021

Abstract
The NCI Center for Global Health convened the 9th Annual Symposium on Global Cancer Research as a virtual 2-day meeting alongside the Consortium of Universities for Global Health Annual Conference, March 10–11, 2021. The virtual format allowed for diverse and inclusive participation by over 400 attendees from 70 countries, 25+ speakers from 12 countries, and sharing of research conducted in 68 countries. The highly interactive 2-day program explored the science and complex considerations around resilience and equity in global cancer research and control. The Symposium convened individuals working in global oncology to discuss trends in global cancer research and control and map out collaborative efforts to move the field forward. The accepted scientific abstracts are published in this special supplement of AACR Cancer Epidemiology, Biomarkers, and Prevention.
Circulating HPV DNA as a Marker for Early Detection of Relapse in Patients with Cervical Cancer
Authors: Jeannot Emmanuelle , Latouche Aurélien , Bonneau Claire , Calméjane Marie-Ange , Beaufort Corine , Ruigrok-Ritstier Kirsten , Bataillon Guillaume , Larbi Chérif Linda , Dupain Célia , Lecerf Charlotte , Popovic Marina , de la Rochefordière Anne , Lecuru Fabrice , Fourchotte Virginie , Jordanova Ekaterina S. , von der Leyen Heiko , Tran-Perennou Carine , Legrier Marie-Emmanuelle , Dureau Sylvain , Raizonville Laurence , Bello Roufai Diana , Le Tourneau Christophe , Bièche Ivan , Rouzier Roman , Berns Els M.J.J. , Kamal Maud , Scholl Suzy 
Published: July 2021

Abstract

Purpose:
Almost all cervical cancers are caused by human papillomavirus (HPV) and patients with advanced stage are at high risk for relapse. Circulating HPV DNA (HPV ctDNA) may serve as a residual tumor marker at the end of chemoradiation or to predict relapse during the follow-up period.

Experimental Design:
We analyzed serum samples from 94 HPV16- or HPV18-related CCs from the BioRAIDs prospective cohort. Samples were collected before and after treatment and during an 18-month follow-up period. Using digital droplet PCR (ddPCR), we assessed the relevance of circulating HPV E7 gene as a marker for residual disease compared to HPV integration site and PIK3CA mutations. Finally, the prognostic impact of circulating HPV E7 gene was assessed with its prediction value of relapse.

Results:
HPV E7 gene was the most sensitive tumor marker, superior to both HPV integration sites and PIK3CA mutations in serum. Circulating HPV DNA (HPV ctDNA) was detected in 63% (59/94) of patients, before treatment. HPV ctDNA detection in serum sample was associated with high FIGO stage (P = 0.02) and para-aortic lymph node involvement (P = 0.01). The level of HPV ctDNA was positively correlated with HPV copy number in the tumor (R = 0.39, P &lt; 0.001). Complete clearance of HPV ctDNA by the end of treatment was significantly associated with a longer PFS (P &lt; 0.0001). Patients with persistent HPV ctDNA in serum relapsed with a median time of 10 months (range, 2–15) from HPV ctDNA detection.

Conclusions:
HPV ctDNA detection is a useful marker to predict relapse in cervical cancer.
See related commentary by Wentzensen and Clarke, p. 5733
A Personalized Mass Spectrometry–Based Assay to Monitor M-Protein in Patients with Multiple Myeloma (EasyM)
Authors: Liyasova Mariya , McDonald Zac , Taylor Paul , Gorospe Kathleen , Xu Xin , Yao Chenyu , Liu Qixin , Yang Liqiang , Atenafu Eshetu G. , Piza Giovanni , Ma Bin , Reece Donna , Trudel Suzanne 
Published: July 2021

Abstract

Purpose:
M-protein is a well-established biomarker used for multiple myeloma monitoring. Current improvements in multiple myeloma treatment created the need to monitor minimal residual disease (MRD) with high sensitivity. Measuring residual levels of M-protein in serum by MS was established as a sensitive assay for disease monitoring. In this study we evaluated the performance of EasyM—a noninvasive, sensitive, MS-based assay for M-protein monitoring.

Experimental Design:
Twenty-six patients enrolled in MCRN-001 clinical trial of two high-dose alkylating agents as conditioning followed by lenalidomide maintenance were selected for the study. All selected patients achieved complete responses (CR) during treatment, whereas five experienced progressive disease on study. The M-protein of each patient was first sequenced from the diagnostic serum using our de novo protein sequencing platform. The patient-specific M-protein peptides were then measured by targeted MS assay to monitor the response to treatment.

Results:
The M-protein doubling over 6 months measured by EasyM could predict the relapse in 4 of 5 relapsed patients 2 to 11 months earlier than conventional testing. In 21 disease-free patients, the M-protein was still detectable by EasyM despite normal FLC and MRD negativity. Importantly, of 72 MRD negative samples with CR status, 62 were positive by EasyM. The best sensitivity achieved by EasyM, detecting 0.58 mg/L of M-protein, was 1,000- and 200-fold higher compared with serum protein electrophoresis and immunofixation electrophoresis, respectively.

Conclusions:
EasyM was demonstrated to be a noninvasive, sensitive assay with superior performance compared with other assays, making it ideal for multiple myeloma monitoring and relapse prediction.
Abstract 1001: Treatment of RB1-intact cancers with CDK4/6 inhibitor combination therapy
Authors: Takahashi Chiaki 
Published: July 2021

Abstract
Synthetic CDK4/6 inhibitors exert anti-tumor effects by forcing RB1 in unphosphorylated status, causing not only cell cycle arrest but also cellular senescence, apoptosis and increased immunogenicity. These agents currently have an indication in advanced breast cancers, and are in clinical trials for many other solid tumors. Hepatocellular carcinoma (HCC) is one of promising targets of CDK4/6 inhibitors. RB family function is often aberrated in the initiation of HCC, however, this is revivable as RB family genes are rarely mutated or deleted in this malignancy. Loss of all Rb family members in Trp53-/- mouse liver resulted in hepatoma reminiscent of human HCC, and re-expression of RB1 sensitized these tumors to a CDK4/6 inhibitor, palbociclib. Introduction of an unphosphorylatable form of RB1 (RB7LP) into HepG2 cells induced effects similar to palbociclib. By screening for compounds that enhance the efficacy of RB7LP, we identified an IKKβ inhibitor. Consistently, RB7LP expression and treatment with palbociclib enhanced IKKα/β phosphorylation and NF-κB activation. Combination therapy using palbociclib with KKβ inhibitor was significantly more effective in HCC treatment than single administration. Moreover, blockade of IKK-NF-κB or AKT pathway enhanced effects of palbociclib on RB1-intact K-Ras mutated lung and colon cancers. These findings provide proof of principle for the treatment of a wide variety of RB1-intact cancers using CDK4/6 inhibitors in combination with an appropriate kinase inhibitor. In this presentation, we will propose a new therapeutic approach to RB1-intact solid tumors.
Citation Format: Chiaki Takahashi. Treatment of RB1-intact cancers with CDK4/6 inhibitor combination therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1001.
Abstract 1013: Mechanistic role of nelfinavir as drug-repurposing strategy against high-grade serous ovarian cancer
Authors: Subeha Mahbuba R. , Goyeneche Alicia A. , Telleria Carlos M. 
Published: July 2021

Abstract
Platinum-based therapy following tumor-debulking surgery has been the backbone of treatment for high-grade serous ovarian cancer (HGSOC) since the 1970s; however, high recurrence of platinum-resistant disease necessitates the development of improved alternative therapies. Repurposing market-available drugs as cancer therapeutics carries the prospect of reducing the timeframe and cost of drug development, posing potential benefits to drug-resistant as well as financially underprivileged patients. Nelfinavir (NFV), an orally available anti-HIV drug, has shown promising effects against diverse cancers as demonstrated through a myriad of pre-clinical studies and clinical trials; however, its remedial benefits against HGSOC are still unclear. In this study, we explored the therapeutic efficacy of NFV on HGSOC cells generated from patients when platinum sensitive or resistant. Acute drug toxicity was assessed by total cell count, percent viability, and the level of hypo-diploid DNA content following 72 h of treatment with NFV. Living cells that tolerated 72 h of NFV treatment were subjected to further drug-free re-incubation for 14-21 days, to assess the residual anti-clonogenic potential of the drug. NFV triggered a dose-depended reduction of total cell number and viability, with a parallel increased hypo-diploid DNA content in both platinum-sensitive and resistant HGSOC cells. A dose-dependent reduction in the number of colonies - originating from cells that evaded acute toxicity - suggested long-term residual toxicity of NFV. Western blot analysis of underlying molecular mechanisms revealed phosphorylation of γH2AX, which suggested NFV-mediated induction of DNA damage. NFV also inhibited proliferation signals by reducing the phosphorylation of Akt and ERK. Moreover, NFV stimulated endoplasmic reticulum (ER) stress in a dose-dependent manner, which was evident from the enhanced expression of GRP78, IRE1α, ATF4, CHOP, and phosphorylated eIF2α. A time-dependent steady increase of ATF4 and CHOP suggested a progressive temporal apoptotic shift during NFV treatment. Finally, the cleavage of caspases-3 and -7 and their downstream effector PARP, in association with increased pro-apoptotic protein BAX, indicated caspase-associated cell-death during NFV-mediated cytotoxicity. In summary, we demonstrated that HGSOC cells of differential platinum sensitivities could be therapeutically targeted by NFV via multipronged mechanistic approaches, encouraging its prospective repurposing benefit against HGSOC.
Citation Format: Mahbuba R. Subeha, Alicia A. Goyeneche, Carlos M. Telleria. Mechanistic role of nelfinavir as drug-repurposing strategy against high-grade serous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1013.
Abstract 1017: Arsenic trioxide reduces the expression of E2F1, cyclin E, and phosphorylation of PI3K signaling molecules in acute leukemia cells
Authors: Tchounwou Paul B. , Kumar Sanjay 
Published: July 2021

Abstract
Arsenic trioxide (ATO) has been used for the treatment of acute promyelocytic leukemia (APL). Although ATO modulates cell cycle progression and apoptosis in APL cells, its exact mechanism of action remains elusive. In this research, we investigated its effects on E2F1, cyclin E, p53, pRb and PI3K signaling molecules by western blotting, immunocytochemistry and/or confocal imaging. We found that ATO inhibited the proliferation of APL cells through down-regulation of E2F1 and cyclin E expression, and stimulation of pRb. It also reduced the interaction of pRb and E2F1with binding to the E2F1 promoter, by stimulating pRb association. ATO also effected the phosphorylation of pRb at S608 and T373 residues and association of E2F1, pRb, and p53, simultaneously. However, in p53-knockdown NB4 cells, ATO did not significantly reduce E2F1 and cyclin E expression. Our findings demonstrate that ATO inhibits APL cell growth through reduced expression of E2F1, cyclin E, and stimulation of pRb. It also effected both interaction and association of E2F1, pRb and p53 by phosphorylation of pRb at T373 and S608 residues and reduced phosphorylation of PI3K signaling molecules. This novel mode of action of ATO in APL cells may be useful for designing new APL drugs.
Citation Format: Paul B. Tchounwou, Sanjay Kumar. Arsenic trioxide reduces the expression of E2F1, cyclin E, and phosphorylation of PI3K signaling molecules in acute leukemia cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1017.
Abstract 1036: Identification of Tofacitinib, Filgotinib and Ruxolitinib on experimental Sjögren's syndrome model in mice
Authors: Yan Ruiqing , Yuan Yanping , Luo Chao , Yangmeng Chuanzhi , Fang Li , Lin Qing 
Published: July 2021

Abstract
Sjögren's syndrome, which is affected hundreds of millions of people worldwide, is a chronic autoimmune disorder characterized by leukocytic infiltration into the exocrine glands, such as the salivary and lacrimal glands. However, the pathological mechanism remains to be elucidated, and urgent need for the novel treatment should still meet. Over the past decades, an extensive progress has been made in establishment of Sjögren's syndrome model in mice, which offers us an invaluable tool to understand SjS pathogenesis and makes it possible to develop the novel drug and treatment. Here, we identified the potential effect of Tofacitinib, Filgotinib and Ruxolitinib on the experimental Sjögren's syndrome model in C57/B6L mice from both In-life study and ex-vivo study at the endpoint. Our data suggest that Tofacitinib, Filgotinib and Ruxolitinib, three JAK inhibtors exhibits the effect on reducing the severity of Sjögren's syndrome in mice, reduces autoantibodies producion and promotes the saliva secretion in mice, which also provides the direction of novel JAK inhibitor on treatment for Sjögren's syndrome.
Citation Format: Ruiqing Yan, Yanping Yuan, Chao Luo, Chuanzhi Yangmeng, Li Fang, Qing Lin. Identification of Tofacitinib, Filgotinib and Ruxolitinib on experimental Sjögren's syndrome model in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1036.
Abstract 1040: Imipridones exhibit synergy with sorafenib, HDAC inhibition, PARP inhibition, and proteasome inhibition in liver cancer cell lines
Authors: Honeyman Joshua N. , Chang Wen-I , Prabhu Varun V. , Allen Joshua E. , Zhou Lanlan , El-Deiry Wafik S. 
Published: July 2021

Abstract
Liver cancer is a significant cause of cancer-related death worldwide. We previously showed that the imipridone class of small molecule therapeutics is active against hepatocellular malignancies. ONC201, the first imipridone to reach clinical trials, antagonizes the G protein-coupled receptor DRD2 and is an agonist of mitochondrial caseinolytic protease ClpP. ONC206 also antagonizes DRD2 and is a ClpP agonist. ONC212 is an agonist of both the orphan G protein-coupled receptor GPR132 and ClpP. We investigated the efficacy of ONC201, ONC206, and ONC212 in combination with histone deacetylase inhibition (HDACi), poly ADP ribose polymerase inhibition (PARPi), proteasome inhibition, and current standard of care multi-kinase inhibitor sorafenib. Liver cancer cell lines Hep3B and HepG2 were treated with ONC201, ONC206, and ONC212 to determine dose-response effect. Both cell lines were also treated with each imipridone in combination with sorafenib. Combination treatment effect was also tested between ONC201 and the HDACi vorinostat, PARPi nariparib, and the proteasome inhibitor marizomib. Cell viability was measured with CellTiter-Glo. Synergy was quantified using the combination index (CI). Protein expression was assessed using Western blot. As has been previously reported, both HepG2 and Hep3B cell lines were sensitive to ONC201 (Hep3B IC50 = 2.29μM; HepG2 IC50 = 2.69μM), ONC206 (Hep3B IC50 = 0.11μM; HepG2 IC50 = 0.15μM), and ONC212 (Hep3B IC50 = 0.07μM; HepG2 IC50 = 0.05μM) administered as single-agent therapy with ONC212 demonstrating the greatest potency. In combination with sorafenib, all three imipridones demonstrated synergy in both cell lines. ONC201 and ONC206 exhibited stronger synergy with CI &lt; 0.3 at multiple dose combinations. ONC201 was also found to exert a synergistic reduction in cell viability when Hep3B and HepG2 cells were treated with vorinostat, nariparib, and marizomib. These results suggest that the imipridone family of small molecules is a novel therapy for liver cancer with efficacy as a single agent and in combination with existing targeted agents. Future studies will clarify the mechanisms of synergy and expand the findings into small animal models.
Citation Format: Joshua N. Honeyman, Wen-I Chang, Varun V. Prabhu, Joshua E. Allen, Lanlan Zhou, Wafik S. El-Deiry. Imipridones exhibit synergy with sorafenib, HDAC inhibition, PARP inhibition, and proteasome inhibition in liver cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1040.
Abstract 1043: Enhancing cytotoxic chemotherapy effects by nintedanib in gastric cancer preclinical models
Authors: Awasthi Niranjan , Schwarz Margaret A. , Hilberg Frank , Schwarz Roderich E. 
Published: July 2021

Abstract
Background: Gastric adenocarcinoma (GAC) remains the 3rd most common cause of cancer mortality in the world. Systemic chemotherapy is a preferred treatment option for advanced and recurrent GAC, but response rates and survival extension remain limited. Tumor angiogenesis plays a critical role in GAC growth, invasion and metastasis. In this study, we determined the antitumor efficacy of nintedanib, a potent triple angiokinase inhibitor for VEGFR-1/2/3, PDGFR-α/β and FGFR-1/2/3, alone or in combination with chemotherapy, in preclinical models of GAC.
Methods: Animal survival and tumor growth studies were performed in 4-6 week-old female NOD/SCID mice with human GAC cell xenografts (MKN-45, KATO-III, SNU-5). The mechanistic evaluation involved Immunohistochemistry and Immunoblot analyses of subcutaneous tumors. In vitro cell viability assays were performed using colorimetric WST-1 reagent.
Results: In MKN-45 cell-derived peritoneal dissemination xenografts, animal survival was improved by nintedanib (33%), docetaxel (100%) or irinotecan (181%), while oxaliplatin, 5-FU and epirubicin had no effect. The addition of nintedanib to docetaxel (157%) or irinotecan (214%) led to a further extension in animal survival. In KATO-III cell-derived xenografts carrying FGFR2 gene amplification, nintedanib monotherapy extended survival much more (209%). Docetaxel and irinotecan effects were again further enhanced by nintedanib. In MKN-45 subcutaneous xenografts, nintedanib, epirubicin, docetaxel or irinotecan reduced tumor growth (range: 68-87%), while 5-FU and oxaliplatin had a smaller effect (40%). The addition of nintedanib to all chemotherapy groups demonstrated a further reduction in tumor growth. Subcutaneous tumor analysis revealed that nintedanib attenuated tumor cell proliferation, reduced tumor vasculature and increased tumor cell death. Nintedanib (10 μM) inhibited in vitro cell proliferation of mutationally different GAC cells by 25% (MKN-45), 75% (KATO-III) or 82% (SNU-5), and confirmed additive inhibitory effects in combinations with chemotherapy agents.
Conclusion: Nintedanib showed notable antitumor efficacy and significantly improved taxane or irinotecan chemotherapy responses. Combination regimens with nintedanib have the potential for improving clinical GAC therapy.
Citation Format: Niranjan Awasthi, Margaret A. Schwarz, Frank Hilberg, Roderich E. Schwarz. Enhancing cytotoxic chemotherapy effects by nintedanib in gastric cancer preclinical models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1043.