tbuckley/cabot-search huggingface dataset:
Upregulation of HSPB1 heat shock gene and ERCC1 gene on serous ovarian cancer cell line in HIPEC in vitro model.
Authors: Warne Pedro Andrade, Bryan Ôrtero Perez Gonçalves, Luciana Maria Silva, Agnaldo Lopes Dasilva Filho
Journal: Journal of Clinical Oncology (2021)

e17559 Background: Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, with the presence of chemoresistance contributing to the poor prognosis. Approximately 80% of cases are diagnosed in stage III C and are treated with cytoreduction surgery followed by adjuvant chemotherapy. However, 70 percent of these patients have pelvic and peritoneal recurrences. Heat Shock Proteins are produced in response to pathophysiological stress and take part in several stages of carcinogenesis, acting primarily as anti-apoptotic agents. They are also implicated in resistance to chemotherapy in several types of tumors. In an attempt to improve oncological results, new therapeutic approaches such as intraperitoneal chemotherapy and HIPEC have been proposed in recent studies with gains in overall survival (OS). However, some questions have not yet been answered. Methods: in the study cultures of ovarian cancer cells were performed TOV-21G (clear cell carcinoma), SK-OV-3 (platinum-resistant serous carcinoma) and OV-90 (high-grade serous). Cell cytotoxicity (MTT) assay was performed. The ovarian cancer cells lines were treated with cisplatin in normothermia (37 degrees Celsius) and cisplatin in hyperthermia (41 degrees Celsius) and a control group treated with PBS saline solution at (37 degrees Celsius and 41 degrees Celsius) for 24 hours followed by new supplementation and a new 3-hours incubation. Clonogenic assay was performed. Then they were submitted to RNA extraction and reverse transcription. qRT-PCR was performed to compare the expression of TRAP1, HSPB1, HSPD1, HSPA1A, HSPA1L and ERCC1 in different treatments. Results: There was no statistical difference in relation to cytotoxicity between treatment with heated cisplatin compared to treatment with normothermia. It was not possible to evaluate the expression of the heat shock genes in the SK-OV3 lineage.The HSPB1, HSPD1, TRAP1 and ERCCC1 genes were positively regulated in OV-90 submitted to hyperthermia in relation to normothermia and there were no significant changes in expression in the TOV-21-G. Conclusions: In conclusion, we suggest that OV-90 Serous ovarian cancer cell line was more susceptibly at hyperthermia by cisplatin. The HSPA1A, HSPA1L, TRAP1 and HSPB1 heat shock genes and ERCC1 genes were upregulated in the heated cisplatin group and contribute to a poor prognosis related to resistance. The HSPB1 and ERCC1 genes had the greatest expression with 1000x higher.Thus, it is necessary to evaluate these genes in a clinical study of HIPEC.
Analysis of hematology and oncology fellowship website content and diversity representation.
Authors: Arun Muthiah, Vanya Aggarwal, Chapman Wei, Chandrasekar Muthiah, Matthew I. Quesenberry, Don S. Dizon
Journal: Journal of Clinical Oncology (2021)

11004 Background: Fellowship in hematology and oncology (HO) is widely sought after but lags behind all other internal medicine subspecialties in attracting applicants underrepresented in medicine (URM). An approach to appealing to URMs involves preexisting in-person strategies but also adapting virtual tools to promote inclusion. Specifically, program websites serve as the first impressions of a program, as well as influence the perception of diversity and inclusion. We evaluated the content and diversity representation of HO program websites to facilitate a generally more informed and URM-considerate recruitment. Methods: The websites of 2019-2020 ACGME accredited HO programs were assessed between June 1st to July 1st, 2020. Data focused on 30 informational categories, derived from published methodology, along with three additional categories concerning diversity, based on suggestions for inclusive graduate medical education recruitment strategies, were compared using two-tailed t tests. We defined websites with 70% or more of the 30 informational categories as “comprehensive websites.” Affiliation with a National Cancer Institute (NCI) Designated Cancer Center, NCI Designated Cancer Center + National Cancer Center Network (NCCN) member institution, and a top 50 ranked cancer hospital by U.S. News was also considered in the analysis. Results: A total of 156 program websites were analyzed: 37.2% NCI; 19.9% NCCN; 29.5% U.S. News ranked. Only 31 (19.9%) were “comprehensive websites,” and 34 (21.8%) had information pertaining to at least one of the diversity categories. There was a significant association between inclusion of diversity content and being a “comprehensive website” (p = 0.001). Compared to those that were neither designated nor ranked, programs designated by NCI, NCCN, or ranked by U.S. News were more likely to have more complete information available (p &lt; 0.001, = 0.008, and &lt; 0.001, respectively). However, only programs ranked by U.S. News were more likely to include information about diversity on their websites (p = 0.006). Conclusions: The vast majority of HO fellowship program websites were not comprehensive, including a lack of diversity and inclusivity content. NCI designation, NCCN participation, and US News ranking were significantly associated with more complete fellowship websites. Given the context of the COVID-19 pandemic in which institution visitation is restricted, program websites may have elevated importance in recruitment. HO programs should direct resources to offering more complete and inclusive websites to better inform applicants, including URM residents.
Micro-organospheres: An automated patient-derived model platform for rapid drug screening of breast cancer.
Authors: Zhaohui Wang, Emilio Cortes-Sanchez, Chieh-Hsiang Yang, Daniel Nelson, Daniel Delubac, Shiaowen David Hsu, Alana Welm, Xiling Shen
Journal: Journal of Clinical Oncology (2021)

e12628 Background: Patient-derived breast cancer (BC) organoids are valuable preclinical models to study patient drug responses, demonstrating good correlations with patients’ clinical outcomes. However, establishment and expansion of such organoids from patient tumors for drug screening is currently a time-consuming and labor-intensive process. A more rapid and high-throughput method will enable broader utility in diagnostics and drug development. Methods: An automated, rapid and scalable microfluidic platform was used to process and develop BC micro-organospheres. Drug sensitivities studies on BC micro-organospheres were performed on day 3 and day 6 using 10-FDA approved drugs, including palbociclib, adriamycin, 5-FU, gemcitabine, methotrexate, everolimus, paclitaxel, docetaxel, ixabepilone, and vinblastine. The responses of micro-organospheres and organoids to the drugs were assessed by CellTiter 3D Glo assay on day 6 after the drug treatment. The growth and establishment of the micro-organospheres by imaging. The drug sensitivity and resistance of the micro-organospheres were analyzed by calculating the percentage cell viability and normalized growth rate inhibition (GRI) and compared to organoids. Results: We successfully established micro-organospheres from eight patient-derived BC organoids with a 100% success rate. The micro-organospheres preserved similar cell morphologies to the bulk organoids. 7/8 micro-organosphere models had similar drug response patterns to organoids between day 3 and day 6 as evident by the GRI heatmap. Specifically, we treated matching micro-organospheres and conventional organoids from two patients with 10 frontline BC chemotherapy drugs, and both showed similar response patterns with GRI heatmap. For the other 6 patient-derived models, the responses of micro-organospheres to docetaxel and everolimus also matched the historical drug responses of in bulk organoid culture with similar GRI heatmap. Conclusions: We have now shown the feasibility of establishing micro-organospheres as a rapid, scalable, and cost-effective platform to study patient-derived BC drug response. This technology has the potential to be used for both diagnostics to guide patient treatment and as a screening platform for new BC drug discovery.
Prognostic understanding, hospitalization, and hospice use among older patients with advanced cancer.
Authors: Kah Poh Loh, Christopher Seplaki, Reza Yousefi Nooraie, Jennifer Leigh Lund, Ronald M. Epstein, Paul Duberstein, Marie Anne Flannery, Eva Culakova, Huiwen Xu, Heidi D. Klepin, Po-Ju Lin, Chandrika Sanapala, Erin Watson, Valerie Targia, Nicholas J. Vogelzang, Elie G. Dib, Adedayo A. Onitilo, Karen Michelle Mustian, Supriya Gupta Mohile
Journal: Journal of Clinical Oncology (2021)

12037 Background: Poor prognostic understanding of curability is associated with lower hospice use in patients with advanced cancer. Little is known if this holds true for older adults specifically. In addition, prognostic understanding are variably assessed and defined in prior studies. We evaluated the associations of poor prognostic understanding and patient-oncologist discordance in both curability and survival estimates with hospitalization and hospice use in older patients with advanced cancer. Methods: We utilized data from a national geriatric assessment cluster-randomized trial (URCC 13070: PI Mohile) that recruited 541 patients aged ≥70 with incurable solid tumor or lymphoma considering any line of cancer treatment and their oncologists. At enrollment, patients and oncologists were asked about their beliefs about cancer curability (options: 100%, &gt; 50%, 50/50, &lt; 50%, 0%, and uncertain) and estimates of patient’s survival (options: 0-6 months, 7-12 months, 1-2 years, 2-5 years, and &gt; 5 years). Non-0% options were considered poor understanding of curability (uncertain was removed from the analysis) and &gt; 5 years was considered poor understanding of survival estimates. Any difference in response options was considered discordant. We used generalized estimating equations to estimate adjusted odds ratios (AOR) assessing associations of poor prognostic understanding and discordance with hospitalization and hospice use at 6 months, adjusting for covariates and practice clusters. Results: Poor prognostic understanding of curability and survival estimates occurred in 59% (206/348) and 41% (205/496) of patients, respectively. Approximately 60% (202/336) and 72% (356/492) of patient-oncologist dyads were discordant in curability and survival estimates, respectively. In the first 6 months after enrollment, 24% were hospitalized and 15% utilized hospice. Poor prognostic understanding of survival estimates was associated with lower odds of hospice use (AOR 0.30, 95% CI 0.16-0.59) (Table). Discordance in survival estimates was associated with greater odds of hospitalization (AOR 1.64, 95% CI 1.01-2.66). Conclusions: Prognostic understanding may be associated with hospitalization or hospice use depending on how patients were queried about their prognosis and whether oncologists’ estimates were considered.[Table: see text]
Nano-immunotherapy for each stage of cancer cellular immunity: which, why, and what?
Authors: Shiyi Zuo, Jiaxuan Song, Jingxuan Zhang, Zhonggui He, Bingjun Sun, Jin Sun
Journal: Theranostics (2021)

Immunotherapy provides a new avenue for combating cancer. Current research in anticancer immunotherapy is primary based on T cell-mediated cellular immunity, which can be divided into seven steps and is named the cancer-immunity cycle. Unfortunately, clinical applications of cancer immunotherapies are restricted by inefficient drug delivery, low response rates, and unmanageable adverse reactions. In response to these challenges, the combination of nanotechnology and immunotherapy (nano-immunotherapy) has been extensively studied in recent years. Rational design of advanced nano-immunotherapies requires in-depth consideration of "which" immune step is targeted, "why" it needs to be further enhanced, and "what" nanotechnology can do for immunotherapy. However, the applications and effects of nanotechnology in the cancer-immunity cycle have not been well reviewed. Herein, we summarize the current developments in nano-immunotherapy for each stage of cancer cellular immunity, with special attention on the which, why and what. Furthermore, we summarize the advantages of nanotechnology for combination immunotherapy in two categories: enhanced efficacy and reduced toxicity. Finally, we discuss the challenges of nano-immunotherapy in detail and provide a perspective.
A <i>Staphylococcus </i>Path to Improved Therapeutics in Atopic Dermatitis
Authors: Tamia A. Harris-Tryon, Shai Bel
Journal: JAMA Dermatology (2021)

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 Dermatology 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 Dermatology journal
Authorship gender equity in global oncology publications.
Authors: Paula Hornstein, Hubert Tuyishime, Miriam Claire Mutebi, Nwamaka Lasebikan, Fidel Rubagumya, Temidayo Fadelu
Journal: Journal of Clinical Oncology (2021)

11008 Background: There is increasing recognition of authorship inequity in academic medicine specialty publications. Analyses in other specialties note that female authors consistently comprise a minority of the first authors and an even smaller percentage of last authors. While this trend may be improving, we hypothesize that significant authorship gender disparities still exist in global oncology journals. Methods: This study comprehensively analyzes the gender distribution of authors for articles published in the Journal of Clinical Oncology Global Oncology (JCO GO), a premier journal in the field, from its inauguration in 2016 to March 2020. A total of 608 articles were identified as matching one of the following six article types: original report, editorial, commentary, case report, special article, and review article. We collected data such as the author’s position, gender, institutional affiliation, and country affiliation. Author gender was categorized as male, female, or indeterminate based on first name probabilities assessed by genderize.io, with a threshold probability of 0.8 based on prior studies. Authorship distribution was analyzed by region and country income level according to the World Bank classification. Results: Of the 608 article first authors, 47.5% were identified as male, while 41.4% were female. Male authors made up a comparatively higher proportion of the 592 last authors; 57.1% were identified as male compared to 32.1% who were female. A similar trend was seen among the 4102 middle authors; 51.4% were identified as male and 38.1% were female. The percentage of authors deemed indeterminate in the cohort was less than 11%. Female authors were more underrepresented among authors from low-income countries; they made up 21.6% of first authors and 9.1% of last authors. Authorship gender by world regions is summarized in Table below. Conclusions: Our analysis shows that authorship inequities persist in global oncology publications. Female authors from lower-income countries, and regions in Sub-Saharan Africa and South Asia, were markedly underrepresented. The underlying reasons for underrepresentation of female authors are multifactorial; further studies are needed to elucidate these factors and to develop and evaluate mitigating strategies.[Table: see text]
Antiangiogenic drug-induced proteinuria as a predictive factor in metastatic colorectal cancer.
Authors: Mihai Vasile Marinca, Diana Cornelia Moisuc, Bogdan Gafton, Alexa Teodora Stratulat, Petru Cianga
Journal: Journal of Clinical Oncology (2021)

e15538 Background: Treatment with bevacizumab, a humanized monoclonal antibody that inhibits vascular endothelial growth factor (VEGF) is known to cause adverse effects such as proteinuria, hypertension, fistulas, and thromboembolic events which, in addition to chemotherapy-induced toxicity, affect the quality of life. However, while bevacizumab-induced hypertension has been linked to increased overall survival, data on proteinuria are controversial. Methods: We performed a retrospective analysis to observe the influence of adverse effects (AEs) on the results of treatment with bevacizumab and chemotherapy in patients with metastatic colorectal cancer (mCRC). Results: Out of the 3497 mCRC patients admitted to our center between 2014 and 2019, 150 met the criteria for inclusion in our analysis. Of these, 50.7% experienced proteinuria and had reached a longer overall survival (OS, 40 versus 25 months, p = 0.015) and progression free survival (PFS, 15 versus 12 months, p = 0.039). Patients with anemia during treatment, regardless of grade, had a 20-month shorter survival. The following groups were identified as having a lower risk of death: patients with proteinuria (HR 0.630; 95% CI 0.424-0.935; p = 0.022), disease control (HR 0.436; 95% CI 0.291-0.653; p&lt; 0.001) and non-metastatic stage at diagnosis (HR 0.477; 95% CI 0.300-0.757; p = 0.002). Anemia was a negative prognostic factor (HR 2.153; 95% CI 1.343-3.454; p = 0.001). Conclusions: Proteinuria seems to be a useful predictive factor in mCRC patients undergoing bevacizumab-based systemic therapy. Since it is already routinely assessed in this clinical setting, proteinuria could be easily integrated in the decision-making process and thus allow physicians to further individualize systemic treatments. Retrospective analyses, as our study, are setting the basis for prospective studies, required for the validation of these results.
Longitudinal sequencing of TCR and circulating tumor DNA revealing radiotherapeutic efficacy and prognosis for non-small cell lung cancer patients with brain metastasis.
Authors: Xiaorong Dong, Lingjuan Chen, Fan Tong, Chunhua Wei, Han Wang, Xuefeng Xia, Yaping Xu, Pian Liu, Zhongxing X. Liao, Jianjun Zhang, David Paul Carbone
Journal: Journal of Clinical Oncology (2021)

e21181 Background: This study aimed to explore cerebrospinal fluid (CSF) and peripheral blood-based liquid biopsy before and after radiotherapy of non-small cell lung cancer (NSCLC) brain metastases. Methods: Thirty NSCLC patients with brain metastases receiving brain radiotherapy were enrolled in this study. CSF and peripheral blood were collected at baseline, 24 hours (T0) and 28 days (T28) after treatment. Somatic mutations and T-cell receptor (TCR) sequences were identified by high-throughput sequencing in both compartments. Results: At baseline, identical mutations shared by paired blood and CSF emerged in nine patients (30%). Dimension reduction analysis identified distinct signatures of V and J gene recombination in blood and CSF TCR sequences. Throughout treatment, both compartments experienced a TCR diversity decrease, however, the degradation of low-abundance clones and the expansion of emerging clones might be two separate processes underwent in blood and CSF, respectively. Diversity changes and ctDNA in blood were possibly related to pulmonary responses, while the increase of maximal clone abundance in CSF might indicate a favorable intracranial response. Blood-ctDNA clearance at T28 was significantly associated with better overall survival (OS, HR = 4.027, p = 0.028) and progression-free survival (PFS, HR = 4.176, p = 0.024), and superior blood TCR diversity at T28 against baseline was associated with longer OS (HR = 5.700, p = 0.039). Combined blood factors achieved a better predictive power (OS, HR = 10.53, p &lt; 0.001; PFS, HR = 4.843, p &lt; 0.001). Patients with increase of maximal clone abundance ≥ 50 in CSF also had a better intracranial PFS (HR = 8.320, p = 0.011). The predictive effects of these markers were independent of other clinical factors in multivariate Cox analysis. Conclusions: CSF and peripheral blood were independent compartments showing disparate genomic and immune signatures. Longitudinal surveillance of both compartments could be a promising method to predict clinical outcomes for NSCLC patients with brain metastases.
Patient out-of-pocket savings with lower-dose trastuzumab.
Authors: Marie S. Dreyer, Alec Kacew, Po-Hung Hsieh, Anthony Serritella, Randall W. Knoebel, Rita Nanda, Garth William Strohbehn, Mark J. Ratain
Journal: Journal of Clinical Oncology (2021)

e18828 Background: Trastuzumab-related costs of human epidermal growth factor receptor 2 (HER2) positive breast cancer treatment are significant, approaching $70,000 per patient in the adjuvant setting alone. Recently developed population pharmacokinetic models demonstrate that therapeutic levels of trastuzumab are maintained despite decreased maintenance dose or dose frequency, potentially improving trastuzumab’s value proposition. In this observational study, we evaluate the potential patient- and health system-level financial implications of low-dose trastuzumab. Methods: We identified 196 individuals who received treatment for HER2-positive breast cancer with trastuzumab or its biosimilars at a single urban comprehensive cancer center between January 1, 2017 and October 31, 2019. We estimate, using publicly available information, patient-experienced out-of-pocket costs using deterministic modeling under different conditions corresponding to changes in dosing practices, geographic site of trastuzumab administration, patient employment status, intent of treatment, and billing procedures, as well as Medicare cost-savings estimates. Results: Both reducing the maintenance dose of trastuzumab from the FDA-labeled dose of 6 mg/kg to 4 mg/kg Q3W and reducing maintenance dose frequency of trastuzumab from 6 mg/kg Q3W to Q4W were each associated with significant patient savings on drug- and administration-related out-of-pocket costs. Depending on billing practice and clinical scenario, patient savings as a percentage of total costs were 9-20% (neoadjuvant), 17-22% (adjuvant), and 14-19% (metastatic) with 6 mg/kg Q4W dosing. Similarly, 4 mg/kg Q3W dosing had savings of 15-25% (neoadjuvant), 19-28% (adjuvant), and 13-28% (metastatic). Utilization of off-label dosing regimens could result in $2.69 billion USD in annual Medicare spending on trastuzumab, an estimated savings of $670-810 million USD. Conclusions: Meaningful patient-level and system-level financial savings in the treatment of HER2-positive breast cancer can be achieved using pharmacokinetically near-equivalent low-dose or reduced frequency maintenance trastuzumab dosing. Given the significant potential savings, further prospective studies aimed at reducing dose or frequency of monoclonal antibodies in the treatment of cancer are warranted.
Therapeutic and diagnostic targeting of fibrosis in metabolic, proliferative and viral disorders
Authors: Alexandros Marios Sofias, Federica De Lorenzi, Quim Peña, Armin Azadkhah Shalmani, Mihael Vucur, Jiong-Wei Wang, Fabian Kiessling, Yang Shi, Lorena Consolino, Gert Storm, Twan Lammers
Journal: Advanced Drug Delivery Reviews (2021)