Physiological media advance cell culture experiments.

The metabolism plays a fundamental role in cellular signaling pathways, but commonly used cell culture media do not reflect physiological metabolite concentrations. The metabolic control hub mammalian target of rapamycin complex 1 (mTORC1) kinase is an illuminating example that it is about time to advance our cell culture to become more physiological and relevant.

Sex reporting of cells used in cancer research: A systematic review.

Sex and gender disparities in biomedical research have been emphasized to improve scientific knowledge applied for the health of both men and women. Despite sex differences in cancer incidence, prognosis, and responses to therapeutic agents, mechanistic explanations at molecular levels are far from enough. Recent studies suggested that cell sex is an important biological variable due to differences in sex chromosome gene expression and differences in events associated with developmental biology. The objective of this study was to analyze the reporting of sex of cells used in cancer research using articles published in Cancer Cell, Molecular Cancer, Journal of Hematology & Oncology, Journal for ImmunoTherapy of Cancer, and Cancer Research in 2020, and to examine whether there exists any sex bias. We found that the percentage of cells with sex notation in the article was 36.5%. Primary cells exhibited higher sex notation compared to cell lines. A higher percentage of female cells were used in cell cultures with sex notation. Also, sex-common cells omitted sex description more often compared to sex-specific cells. None of the cells isolated from embryo and esophagus reported the cell sex in the article. Our results indicate cell sex report in cancer research is limited to a small proportion of cells used in the study. These results call for acknowledging the sex of cells to increase the applicability of biomedical research discoveries.

Advancing rare cancer research by MALDI mass spectrometry imaging: Applications, challenges, and future perspectives in sarcoma.

MALDI mass spectrometry imaging (MALDI imaging) uniquely advances cancer research, by measuring spatial distribution of endogenous and exogenous molecules directly from tissue sections. These molecular maps provide valuable insights into basic and translational cancer research, including tumor biology, tumor microenvironment, biomarker identification, drug treatment, and patient stratification. Despite its advantages, MALDI imaging is underutilized in studying rare cancers. Sarcomas, a group of malignant mesenchymal tumors, pose unique challenges in medical research due to their complex heterogeneity and low incidence, resulting in understudied subtypes with suboptimal management and outcomes. In this review, we explore the applicability of MALDI imaging in sarcoma research, showcasing its value in understanding this highly heterogeneous and challenging rare cancer. We summarize all MALDI imaging studies in sarcoma to date, highlight their impact on key research fields, including molecular signatures, cancer heterogeneity, and drug studies. We address specific challenges encountered when employing MALDI imaging for sarcomas, and propose solutions, such as using formalin-fixed paraffin-embedded tissues, and multiplexed experiments, and considerations for multi-site studies and digital data sharing practices. Through this review, we aim to spark collaboration between MALDI imaging researchers and clinical colleagues, to deploy the unique capabilities of MALDI imaging in the context of sarcoma.

Gsw-fi: a GLM model incorporating shrinkage and double-weighted strategies for identifying cancer driver genes with functional impact.

BACKGROUND: Cancer, a disease with high morbidity and mortality rates, poses a significant threat to human health. Driver genes, which harbor mutations accountable for the initiation and progression of tumors, play a crucial role in cancer development. Identifying driver genes stands as a paramount objective in cancer research and precision medicine. RESULTS: In the present work, we propose a method for identifying driver genes using a Generalized Linear Regression Model (GLM) with Shrinkage and double-Weighted strategies based on Functional Impact, which is named GSW-FI. Firstly, an estimating model is proposed for assessing the background functional impacts of genes based on GLM, utilizing gene features as predictors. Secondly, the shrinkage and double-weighted strategies as two revising approaches are integrated to ensure the rationality of the identified driver genes. Lastly, a statistical method of hypothesis testing is designed to identify driver genes by leveraging the estimated background function impacts. Experimental results conducted on 31 The Cancer Genome Altas datasets demonstrate that GSW-FI outperforms ten other prediction methods in terms of the overlap fraction with well-known databases and consensus predictions among different methods. CONCLUSIONS: GSW-FI presents a novel approach that efficiently identifies driver genes with functional impact mutations using computational methods, thereby advancing the development of precision medicine for cancer.

Translational PK/PD framework for antibody-drug conjugates to inform drug discovery and development.

(171/200)ADCs represent a transformative class of medicine that combines the specificity of monoclonal antibodies with the potency of highly cytotoxic agents through linkers, aiming to enhance the therapeutic index of cytotoxic drugs. Given the complex molecular structures of ADCs, combining the molecular characteristics of small-molecule drugs and those of large-molecule biotherapeutics, there are several unique considerations when designing nonclinical-to-clinical PK/PD translation strategies.This complexity also demands a thorough understanding of the ADC's components-antibody, linker, and payload-to the overall toxicological, PK/PD, and efficacy profile. ADC development is a multidisciplinary endeavor requiring a strategic integration of nonclinical safety, pharmacology, and PK/PD modeling to translate from bench to bedside successfully.The ADC development underscores the necessity for a robust scientific foundation, leveraging advanced analytical and modeling tools to predict human responses and optimize therapeutic outcomes.This review aims to provide an ADC translational PK/PD framework by discussing unique aspects of ADC nonclinical to clinical PK translation, starting dose determination, and leveraging PK/PD modeling for human efficacious dose prediction and potential safety mitigation.

The impact of a regionally based translational cancer research collaborative in Australia using the FAIT methodology.

BACKGROUND: Translating research, achieving impact, and assessing impact are important aspirations for all research collaboratives but can prove challenging. The Hunter Cancer Research Alliance (HCRA) was funded from 2014 to 2021 to enhance capacity and productivity in cancer research in a regional centre in Australia. This study aimed to assess the impact and benefit of the HCRA to help inform future research investments of this type. METHOD: The Framework to Assess the Impact from Translational health research (FAIT) was selected as the preferred methodology. FAIT incorporates three validated methodologies for assessing impact: 1) Modified Payback; 2) Economic Analysis; and 3) Narrative overview and case studies. All three FAIT methods are underpinned by a Program Logic Model. Data were collected from HCRA and the University of Newcastle administrative records, directly from HCRA members, and website searches. RESULTS: In addition to advancing knowledge and providing capacity building support to members via grants, fellowships, scholarships, training, events and targeted translation support, key impacts of HCRA-member research teams included: (i) the establishment of a regional biobank that has distributed over 13,600 samples and became largely self-sustaining; (ii) conservatively leveraging $43.8 M (s.a.$20.5 M - $160.5 M) in funding and support from the initial $9.7 M investment; (iii) contributing to clinical practice guidelines and securing a patent for identification of stem cells for endometrial cell regeneration; (iv) shifting the treatment paradigm for all tumour types that rely on nerve cell innervation, (v) development and implementation of the world's first real-time patient treatment verification system (Watchdog); (vi) inventing the effective 'EAT' psychological intervention to improve nutrition and outcomes in people experiencing radiotherapy for head and neck cancer; (vi) developing effective interventions to reduce smoking rates among priority groups, currently being rolled out to disadvantaged populations in NSW; and (vii) establishing a Consumer Advisory Panel and Consumer Engagement Committee to increase consumer involvement in research. CONCLUSION: Using FAIT methodology, we have demonstrated the significant impact and downstream benefits that can be achieved by the provision of infrastructure-type funding to regional and rural research collaboratives to help address inequities in research activity and health outcomes and demonstrates a positive return on investment.

Community Trust, Attitudes and Preferences Related to Participation in Cancer Research in South Carolina.

African American adults have the highest mortality rate for most cancers in the United States, and meaningful, community-driven research is needed to inform optimal strategies for addressing these disparities. Unfortunately, research mistrust, often driven by historical inequities, is well-documented among African Americans.This study explored trust, attitudes, and preferences regarding participation in cancer research activities among primarily African American and other medically underserved communities in South Carolina from August 2020 to December 2021. Trust was measured using the Trust in Medical Researchers Scale (TMRS).The mean TMRS score for all study participants (N = 179) was 26.54 (SD 7.57) out of 48 (maximum possible score). Significant differences in mean values of the TMRS scores were only observed for gender (p = 0.0056) and race (p < 0.0001), with White participants and males reporting higher levels of trust in medical researchers. Overall, 52.5% of participants were somewhat likely or likely to volunteer to participate in a cancer research opportunity, with White participants (73.81%) being more likely to participate in cancer research compared to African American participants (45.74%) (p = 0.0054). Furthermore, participants were most willing to provide saliva (80.85%) and urine samples (80.85%), new blood samples (60.64%), stool samples (54.26%), medical records or laboratory results (52.13%) and least willing to allow left-over blood, tissue, or other fluids from medical procedures to be used for research (50%).These results provide evidence of the need for concerted programmatic efforts to build trust in cancer researchers, particularly among females and African American adults.

Factors influencing the research impact in cancer research: a collaboration and knowledge network analysis.

BACKGROUND: Cancer is a major public health challenge globally. However, little is known about the evolution patterns of cancer research communities and the influencing factors of their research capacity and impact, which is affected not only by the social networks established through research collaboration but also by the knowledge networks in which the research projects are embedded. METHODS: The focus of this study was narrowed to a specific topic - 'synthetic lethality' - in cancer research. This field has seen vibrant growth and multidisciplinary collaboration in the past decade. Multi-level collaboration and knowledge networks were established and analysed on the basis of bibliometric data from 'synthetic lethality'-related cancer research papers. Negative binomial regression analysis was further applied to explore how node attributes within these networks, along with other potential factors, affected paper citations, which are widely accepted as proxies for assessing research capacity and impact. RESULTS: Our study revealed that the synthetic lethality-based cancer research field is characterized by a knowledge network with high integration, alongside a collaboration network exhibiting some clustering. We found significant correlations between certain factors and citation counts. Specifically, a leading status within the nation-level international collaboration network and industry involvement were both found to be significantly related to higher citations. In the individual-level collaboration networks, lead authors' degree centrality has an inverted U-shaped relationship with citations, while their structural holes exhibit a positive and significant effect. Within the knowledge network, however, only measures of structural holes have a positive and significant effect on the number of citations. CONCLUSIONS: To enhance cancer research capacity and impact, non-leading countries should take measures to enhance their international collaboration status. For early career researchers, increasing the number of collaborators seems to be more effective. University-industry cooperation should also be encouraged, enhancing the integration of human resources, technology, funding, research platforms and medical resources. Insights gained through this study also provide recommendations to researchers or administrators in designing future research directions from a knowledge network perspective. Focusing on unique issues especially interdisciplinary fields will improve output and influence their research work.

Characterisation of Canine and Feline Breast Tumours, Their Metastases, and Corresponding Primary Cell Lines Using LA-REIMS and DESI-MS Imaging.

Breast cancer, a complex disease with a significant prevalence to form metastases, necessitates novel therapeutic strategies to improve treatment outcomes. Here, we present the results of a comparative molecular study of primary breast tumours, their metastases, and the corresponding primary cell lines using Desorption Electrospray Ionisation (DESI) and Laser-Assisted Rapid Evaporative Ionisation Mass Spectrometry (LA-REIMS) imaging. Our results show that ambient ionisation mass spectrometry technology is suitable for rapid characterisation of samples, providing a lipid- and metabolite-rich spectrum within seconds. Our study demonstrates that the lipidomic fingerprint of the primary tumour is not significantly distinguishable from that of its metastasis, in parallel with the similarity observed between their respective primary cell lines. While significant differences were observed between tumours and the corresponding cell lines, distinct lipidomic signatures and several phospholipids such as PA(36:2), PE(36:1), and PE(P-38:4)/PE(O-38:5) for LA-REIMS imaging and PE(P-38:4)/PE(O-38:5), PS(36:1), and PI(38:4) for DESI-MSI were identified in both tumours and cells. We show that the tumours' characteristics can be found in the corresponding primary cell lines, offering a promising avenue for assessing tumour responsiveness to therapeutic interventions. A comparative analysis by DESI-MSI and LA-REIMS imaging revealed complementary information, demonstrating the utility of LA-REIMS in the molecular imaging of cancer.

Topology and Dynamics of Transcriptome (Dys)Regulation.

RNA transcripts play a crucial role as witnesses of gene expression health. Identifying disruptive short sequences in RNA transcription and regulation is essential for potentially treating diseases. Let us delve into the mathematical intricacies of these sequences. We have previously devised a mathematical approach for defining a "healthy" sequence. This sequence is characterized by having at most four distinct nucleotides (denoted as nt≤4). It serves as the generator of a group denoted as fp. The desired properties of this sequence are as follows: fp should be close to a free group of rank nt-1, it must be aperiodic, and fp should not have isolated singularities within its SL2(C) character variety (specifically within the corresponding Groebner basis). Now, let us explore the concept of singularities. There are cubic surfaces associated with the character variety of a four-punctured sphere denoted as S24. When we encounter these singularities, we find ourselves dealing with some algebraic solutions of a dynamical second-order differential (and transcendental) equation known as the Painlevé VI Equation. In certain cases, S24 degenerates, in the sense that two punctures collapse, resulting in a "wild" dynamics governed by the Painlevé equations of an index lower than VI. In our paper, we provide examples of these fascinating mathematical structures within the context of miRNAs. Specifically, we find a clear relationship between decorated character varieties of Painlevé equations and the character variety calculated from the seed of oncomirs. These findings should find many applications including cancer research and the investigation of neurodegenative diseases.

Partnership in Cancer Research (PCAR) Program Increases Medical Student Knowledge and Confidence to Perform Cancer Research.

Arkansas has a high cancer burden, and a pressing need exists for more medical students to pursue oncology as a career. The Partnership in Cancer Research (PCAR) program provides a summer research experience at the University of Arkansas for Medical Sciences for 12 medical students who have completed their first year of medical training. A majority of participants spend time pursuing cancer research in basic science, clinical, or community-based research. Students report on their research progress in an interactive "Live from the Lab!" series and assemble a final poster presentation describing their findings. Other activities include participation in a moderated, cancer-patient support group online, lecture series on cancer topics, medical simulations, palliative care clinic visit, "Death Over Dinner" event, and an entrepreneurship competition. Students completed surveys over PCAR's first 2 years in operation to evaluate all aspects of the program. Surveys reveal that students enthusiastically embraced the program in its entirety. This was especially true of the medical simulations which received the highest evaluations. Most significantly, surveys revealed that the program increased cancer knowledge and participant confidence to perform cancer research.

Mentoring Minority Cancer Researchers of Tomorrow: Comparison of the Face-to-Face, Virtual, and Hybrid Training Methods of the CaRE2 Summer Cancer Research Education and Training Program.

In our previous publication, we reported a framework to develop an undergraduate cancer research training program at Florida A&M University (FAMU) under the umbrella of the Florida-California Cancer Research, Education, and Engagement (CaRE2) Health Equity Center activity by harnessing the resources available at FAMU, the University of Florida (UF), and the University of Southern California (USC) Cancer Centers. The implementation of the CaRE2 face-to-face training platform was dramatically affected by the COVID-19 pandemic during the summer of 2020 and 2021 training periods. However, a concerted effort was made to restructure the face-to-face training model into virtual and hybrid training methods to maintain the continuity of the program during the pandemic. This article compared the three methods to identify the best platform for training URM students in cancer disparity research. The program's effectiveness was measured through motivation, experiences, and knowledge gained by trainees during and one year after the completion of the program. The results showed that the participants were highly positive in their feedback about the professional and academic values of the program. Although the virtual and hybrid methods experienced significant challenges during the pandemic, the hybrid training module offered an "above average" effectiveness in performance, like the face-to-face mentoring platform in mentoring URM students in cancer disparity research.

Associations Between Race/Ethnicity, Language, and Enrollment on Cancer Research Studies.

PURPOSE: The objective of this study was to determine whether differences in patients' race/ethnicity, preferred language, and other factors were associated with patient enrollment in oncology research studies. PATIENTS AND METHODS: We conducted a retrospective cross-sectional analysis of all adults (>18 and ≤90) seen at a large, metropolitan cancer center from 2005 to 2015, examining if enrollment to a research study, varied by race/ethnicity, preferred language, comorbidities, gender, and age. RESULTS: A total of 233 604 patients were available for initial analysis. Of these, 93 278 (39.9%) were enrolled in a research protocol (therapeutic and non-therapeutic studies). Patients who self-reported their race/ethnicity as Native, Other, Unknown, or Refuse to Answer were less likely to be enrolled on a study. Patients with one or more comorbidities, and those whose preferred language was English, were more likely to be enrolled on a research study. A logistic regression model showed that, although Non-Hispanic Black patients were more likely to have one or more comorbidities and had a higher proportion of their subset selecting English as their preferred language, they were less likely to be enrolled on a study, than our largest population, Non-Hispanic/White patients. CONCLUSIONS: We identified differences in research study enrollment based on preferred language, and within race/ethnicity categories including Native-Populations, Other, Unknown or Refuse to Answer compared to Non-Hispanic/White patients. We also highlighted the lower odds of enrollment among Non-Hispanic/Black patients, in the setting of factors such as comorbidities and English language preference, which were otherwise found to be positive predictors of enrollment. Further investigation is needed to design targeted interventions to reduce disparities in oncology research study enrollment, with particular focus on language diversity.

Engaging community members in cancer research: an assessment of an NCI-designated cancer center.

PURPOSE: Despite the importance of engaging community members in research, multiple barriers exist. We conducted a mixed-methods evaluation to understand the opportunities and challenges of engaging community members in basic, clinical, translational, and population science research. METHODS: We designed a survey and an interview guide based on the constructs of the Consolidated Framework for Implementation Research. Surveys were distributed electronically to all cancer center investigators and interviews were conducted virtually with a select group of basic, clinical, and population science investigators. Survey data (n = 77) were analyzed across all respondents using frequency counts and mean scores; bivariate analyses examined differences in responses by research program affiliation, gender, race, and faculty rank. Interviews (n = 16) were audio recorded, transcribed verbatim, and analyzed using a reflective thematic approach. RESULTS: There was strong agreement among investigators that "Community engagement in research will help the SKCC address cancer disparities in the catchment area" (M 4.2, SD 0.9) and less agreement with items such as "I know how to find and connect with community members who I can engage in my research" (M 2.5, SD 1.3). Investigators mentioned challenges in communicating complex science to a lay audience but were open to training and workshops to acquire skills needed to integrate community members into their research. CONCLUSION: Cancer centers should develop and promote training and collaborative opportunities for investigators and community members. Overcoming challenges will lead to more patient- and community-centered cancer research in the future.

Evaluation of a 'plug and play' nanoflow liquid chromatography system for MS-based proteomic characterization of clinical FFPE specimens.

INTRODUCTION: Proteomic analysis of formalin-fixed paraffin-embedded (FFPE) tumor tissue specimens has gained interest in the last 5 years due to technological advances and improved sample collection, as well as biobanking for clinical trials. The real-world implementation of clinical proteomics to these specimens, however, is hampered by tedious sample preparation steps and long instrument acquisition times. AREAS COVERED: To advance the translation of quantitative proteomics into the clinic, we are comparing the performance of the leading commercial nanoflow liquid chromatography (nLC) system (based on literature reviews), the Easy-nLC 1200 (Thermo Fisher Scientific, Waltham, MA, U.S.A.), to the Evosep One HPLC (Evosep Biosystems, Odense, Denmark). We measured FFPE-tissue digests from 21 biological replicates with a similar gradient on both of the LC systems while keeping the on-column amount (1 µg total protein) and the single-shot data-dependent acquisition-based MS/MS method constant. EXPERT OPINION: Overall, the Evosep One facilitates robust and sensitive high-throughput sample acquisition, making it suitable for clinical MS. We found the Evosep One to be a useful platform for positioning mass spectrometry-based proteomics in the clinical setting. The clinical application of nLC/MS will inform clinical decision-making in oncology and other diseases.

Generation, evolution, interfering factors, applications, and challenges of patient-derived xenograft models in immunodeficient mice.

Establishing appropriate preclinical models is essential for cancer research. Evidence suggests that cancer is a highly heterogeneous disease. This follows the growing use of cancer models in cancer research to avoid these differences between xenograft tumor models and patient tumors. In recent years, a patient-derived xenograft (PDX) tumor model has been actively generated and applied, which preserves both cell-cell interactions and the microenvironment of tumors by directly transplanting cancer tissue from tumors into immunodeficient mice. In addition to this, the advent of alternative hosts, such as zebrafish hosts, or in vitro models (organoids and microfluidics), has also facilitated the advancement of cancer research. However, they still have a long way to go before they become reliable models. The development of immunodeficient mice has enabled PDX to become more mature and radiate new vitality. As one of the most reliable and standard preclinical models, the PDX model in immunodeficient mice (PDX-IM) exerts important effects in drug screening, biomarker development, personalized medicine, co-clinical trials, and immunotherapy. Here, we focus on the development procedures and application of PDX-IM in detail, summarize the implications that the evolution of immunodeficient mice has brought to PDX-IM, and cover the key issues in developing PDX-IM in preclinical studies.

Addressing cancer care in low- to middle-income countries: a call for sustainable innovations and impactful research.

Most new cancer cases are currently arising in low- and middle-income countries, where their outcomes are significantly poorer compared to high-income countries. Innovative solutions are imperiously needed to prevent, detect early, and manage cancer in low- and middle-income countries, aiming to improve the chances of survival.

Inductively Coupled Plasma Mass Spectrometry─A Valid Method for the Characterization of Metal Conjugates in View of the Development of Radiopharmaceuticals.

This study addresses the question whether inductively coupled plasma mass spectrometry (ICP-MS) can be used as a method for the in vitro and in vivo characterization of non-radioactive metal conjugates to predict the properties of analogous radiopharmaceuticals. In a "proof-of-concept" study, the prostate-specific membrane antigen (PSMA)-targeting [175Lu]Lu-PSMA-617 and [159Tb]Tb-PSMA-617 were compared with their respective radiolabeled analogues, [177Lu]Lu-PSMA-617 (PLUVICTO, Novartis) and [161Tb]Tb-PSMA-617. ICP-MS and conventional γ-counting of the cell samples revealed almost identical results (<6% absolute difference between the two technologies) for the in vitro uptake and internalization of the (radio)metal conjugates, irrespective of the employed methodology. In vivo, an equal uptake in PSMA-positive PC-3 PIP tumor xenografts was determined 1 h after the injection of [175Lu]Lu-/[177Lu]Lu-PSMA-617 (41 ± 6% ID/g and 44 ± 12% IA/g, respectively) and [159Tb]Tb-/[161Tb]Tb-PSMA-617 (44 ± 5% ID/g and 44 ± 5% IA/g, respectively). It was further revealed that it is crucial to use the same ratios of the (radio)metal-labeled and unlabeled ligands for both methodologies to obtain equal data in organs in which receptor saturation was reached such as the kidneys (12 ± 2% ID/g vs 10 ± 1% IA/g, 1 h after injection). The data of this study demonstrate that the use of high-sensitivity ICP-MS allows reliable and predictive quantification of compounds labeled with stable metal isotopes in cell and tissue samples obtained in preclinical studies. It can, hence, be employed as a valid alternative to the state-of-the-art γ-counting methodology to detect radioactive ligands.

A tripartite approach toward ending cancer as we know it, for everyone: An American Cancer Society perspective.

Gaps in the cancer care continuum are vast, both in the United States and globally. The American Cancer Society orchestrates an integrated, tripartite approach toward improving the lives of cancer patients and their families through research, advocacy, and patient support. With a focus on eradicating cancer disparities, the American Cancer Society aims to scale and deploy best practices worldwide through partnerships, to ensure everyone has an opportunity to prevent, detect, treat, and survive cancer.

The African Research Group for Oncology: A decade fostering colorectal cancer research in Nigeria.

The African Research Group for Oncology (ARGO) was formed in 2013 to undertake methodologically rigorous cancer research in Nigeria, and to strengthen cancer research capacity in the country through training and mentorship of physicians, scientists, and other healthcare workers. Here, we describe how ARGO's work in colorectal cancer (CRC) has evolved over the past decade. This includes the consortium's scientific contributions to the understanding of CRC in Nigeria and globally and its research capacity-building program.