Biology subjects

Furukawa, E.

Publications and source records attributed to Furukawa, E..

5 recordsLinked to original sources

bioRxiv2025

tugMedi: simulator of cancer-cell evolution for personalized medicine based on the genomic data of patients

Cancer comprehensive genomic profiling tests are increasingly used, but drug response rates remain limited. Simulations forecasting cancer progression could aid targeted therapies; however, existing simulations focus mainly on basic biology. We present tugMedi, a cancer-cell evolution simulator designed for cancer genome medicine. By integrating patient-specific genomic and imaging data, tugMedi reconstructs each tumors genomic features and growth behavior, enabling real-time predictions of clonal dynamics under virtual drug regimens. tugMedi explicitly models copy number alterations and SNVs on parental chromosomes in recessive and dominant modes, capturing loss-of-heterozygosity and yielding precise variant allele frequencies and tumor contents. It handles mutations in cancer-related genes with real exon-intron structures by a fast algorithm. For TCGA samples, it provided ensemble predictions of clonal dynamics, allowing extraction of drug response, tumor-size shrinkage rates, and time to recurrence under specific drug conditions. tugMedi represents a first step toward simulation-driven genome medicine based on a patient-derived virtual tumor.

bioinformatics↗

bioRxiv2023

Global changes in open reading frame dominance of RNAs during cancer initiation and progression

Cancer cells express unique RNA transcripts; however, the factors determining their translation have remained unclear. We recently developed open reading frame (ORF) dominance as a measure that correlates with coding potential of RNAs. Upon calculating the ORF dominance of cancer-specific transcripts across 24 human tumor types, 14 exhibited significantly higher ORF dominance in cancer than in normal tissues. In organoid-based mouse genetic models, ORF dominance increased with carcinogenesis. Gene ontology analysis revealed that gene sets with increased ORF dominance were associated with cell proliferation, while those with decreased ORF dominance were linked to DNA damage response. Translatome analyses demonstrated that elevated ORF dominance during carcinogenesis resulted in higher translation frequencies of ribosome-bound RNAs. As cancer progressed, ORF dominance showed that the boundary between coding and noncoding transcripts became blurred prior to distant metastasis, indicating decreased proliferative cell populations and increased generation of RNA isoforms that potentially translate neoantigens before the development of metastatic tumors. These findings suggest that cancer evolution leads to dynamic changes in ORF dominance, resulting in global translational alterations in transcriptomes.

cancer biology↗

bioRxiv2019

Association between uncontrolled eating and caudate responses to reward cues

Reward sensitivity has been hypothesized to play a significant role in a range of eating behaviors, including overeating. Previous functional magnetic resonance imaging (fMRI) findings in overweight individuals indicate heightened responses to food, but also to other reward types, suggesting generalized overactivity of the reward system. The current fMRI study investigated the relationship between general reward sensitivity and eating behavior in normal-weight individuals, while controlling for trait impulsivity. Participants were young adults, some demonstrating ADHD symptoms, allowing for a range of impulsivity profiles. A classical conditioning task was used to measure striatal responses to monetary reward stimuli. Uncontrolled eating scores from the Three Eating Factor Questionnaire were positively correlated with caudate responses to reward predicting cues. This association was not explained by self-reported impulsivity. The current findings provide support for heightened reward anticipation as a neural phenotype contributing to overeating.

neuroscience↗

bioRxiv2019

Single-cell DNA and RNA sequencing reveals the dynamics of intra-tumor heterogeneity in a colorectal cancer model

Intra-tumor heterogeneity (ITH) encompasses cellular differences in tumors and is related to clinical outcomes, such as drug resistance. However, little is known about the dynamics of ITH, owing to the lack of time-series analysis at the single-cell level. We performed single-cell exome and transcriptome sequencing of 200 cells and investigated how ITH is generated from one single cell in a mouse colorectal cancer model. The ITH of the transcriptome increased after transplantation from cultured organoids, while that of the exome decreased. Mutations generated in the culture did not greatly change at the transplantation at the bulk-cell level. The RNA ITH increase was due to the emergence of new transcriptional subpopulations. In contrast to the initial cells expressing mesenchymal-marker genes, new subpopulations repressed these genes at transplantation. Analyses of colorectal cancer data from The Cancer Genome Atlas revealed a high proportion of metastatic cases in human subjects with expression patterns similar to the new cell subpopulations in mouse. These results suggest that the birth of transcriptional subpopulations may be a key for adaptation to drastic micro-environmental changes when cancer cells have sufficient genetic alterations at later tumor stages. This study revealed an evolutionary dynamics of single-cell RNA and DNA changes in tumor progression, giving insights into the mesenchymal-epithelial transformation of tumor cells at metastasis in colorectal cancer.

genomics↗

bioRxiv2019

Development of Pavlovian-to-instrumental transfer (PIT) task to examine the effects of reward-predicting cues on behavioral activation in young adults

There is a growing recognition that much of human behavior is governed by the presence of classically conditioned cues. The Pavlovian-to-Instrumental Transfer (PIT) paradigm offers a way to measure the effects of classically conditioned stimuli on behavior. In the current study, a novel PIT paradigm was developed for use in conjunction with an fMRI classical conditioning task. This could allow for a measurement of BOLD responses to anticipated rewards, unconfounded by operant responses, while providing a behavioral measure of conditioning effects. Twenty-four healthy young adults completed 1) instrumental training, 2) Pavlovian conditioning, and 3) Transfer test. During instrumental training, participants learned to apply force on a handgrip to win money from slot machines pictured on a computer screen. During Pavlovian conditioning, slot machines appeared with one of two abstract symbols (cues), one symbol was predictive of monetary reward. During the Transfer test, participants again applied force on a handgrip to win more money. This time, slot machines were presented with the Pavlovian cues, but with the outcomes hidden. The results indicated increased effort on the instrumental task, i.e., higher response frequency and greater force, in the presence of a reward-predicting cue. Our findings add to a growing number of studies demonstrating PIT effects in humans. This paradigm was proved to be useful in measuring the effects of a conditioned stimulus on behavioral activation.

neuroscience↗