Publishing type：Research paper (scientific journal)   Publisher：International Institute of Anticancer Research  

DOI： 10.21873/invivo.14090

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

Abstract

Background

Early tumor shrinkage and depth of response have emerged as potential prognostic indicators in metastatic colorectal cancer (CRC). However, their associations with overall survival, progression-free survival (PFS), and postprogression survival in patients receiving anti–epidermal growth factor receptor (EGFR) antibodies or bevacizumab remain unclear.

Methods

We analyzed 3219 treatment-naive patients with RAS wild-type metastatic CRC from 8 randomized studies (CRYSTAL, OPUS, PRIME, CAIRO2, CALGB80405, WJOG4407G, ATOM, PARADIGM) in the Aid and Research in Digestive Cancerology database. Early tumor shrinkage was defined as a 20% or more reduction in tumor size at 8 ± 2 weeks, whereas depth of response was assessed by maximum tumor shrinkage at nadir. Cox regression models evaluated the associations of early tumor shrinkage and depth of response with overall survival, PFS, and postprogression survival, adjusting for confounders. A 2-sided test was conducted with a significance level of .05.

Results

Early tumor shrinkage and depth of response substantially stratified overall survival, PFS, and postprogression survival outcomes across all treatment groups. Early tumor shrinkage positivity was associated with improved overall survival, PFS, and postprogression survival in anti-EGFR and bevacizumab-based therapies, with a trend toward better outcomes in the anti-EGFR group. The depth of response analysis revealed optimal cutoff values of 0.55 for anti-EGFR–based therapy and 0.47 for bevacizumab-based therapy to achieve a median overall survival of approximately 32 months.

Conclusions

Early tumor shrinkage and depth of response serve as valuable prognostic markers in RAS wild-type metastatic CRC, particularly for patients treated with anti-EGFR antibodies. These findings highlight the potential role of early tumor shrinkage and depth of response in guiding treatment strategies and improving outcomes for patients with CRC.

DOI： 10.1093/jncics/pkaf042

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Other Link： https://academic.oup.com/jncics/article-pdf/9/3/pkaf042/63012434/pkaf042.pdf

Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.lungcan.2025.108437

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.esmorw.2024.100072

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.clcc.2024.04.001

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Language：English   Publishing type：Research paper (scientific journal)  

Osteoporosis is characterized by weakened bone microstructure and loss of bone mass. Current diagnostic criteria for osteoporosis are based on the T-score, which is a measure of bone mineral density. However, osteoporotic fragility fractures can occur regardless of the T-score, underscoring the need for additional criteria for the early detection of patients at fracture risk. To identify indicators of reduced bone strength, we performed serum proteomic analysis using data-independent acquisition mass spectrometry with serum samples from two patient groups, one with osteoporosis but no fractures and the other with osteopenia and fragility fractures. Collective evaluation of the results identified six serum proteins that changed to a similar extent in both patient groups compared with controls. Of these, extracellular matrix protein 1 (ECM1), which contributes to bone formation, showed the most significant increase in serum levels in both patient groups. An ELISA-based assay suggested that ECM1 could serve as a serum indicator of the need for therapeutic intervention; however, further prospective studies with a larger sample size are necessary to confirm these results. The present findings may contribute to the provision of early and appropriate therapeutic strategies for patients at risk of osteoporotic fractures. SIGNIFICANCE: This study aimed to identify objective serum indicators of the need for therapeutic intervention in individuals at risk of osteoporotic fracture. Comprehensive proteome analyses of serum collected from patients with osteoporosis but no fractures, patients with osteopenia and fragility fractures, and controls were performed by data-independent acquisition mass spectrometry. Collective evaluation of the proteome analysis data and ELISA-based assays identified serum ECM1 as a potential objective marker of the risk of fragility fractures in patients with osteoporosis or osteopenia. The findings are an important step toward the development of appropriate bone health management methods to improve well-being and maintain quality of life.

DOI： 10.1016/j.jprot.2024.105166

PubMed

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Abstract

The molecular mechanisms associated with spaceflight‐induced biological adaptations that may affect many healthy tissue functions remain poorly understood. In this study, we analyzed temporal changes in the serum proteome of six astronauts during prolonged spaceflight missions using quantitative comprehensive proteome analysis performed with the data‐independent acquisition method of mass spectrometry (DIA‐MS). All six astronauts participated in a spaceflight mission for approximately 6 months and showed a decreasing trend in T‐scores at almost all sites where dual‐energy X‐ray absorptiometry scans were performed. DIA‐MS successfully identified 624 nonredundant proteins in sera and further quantitative analysis for each sampling point provided information on serum protein profiles closely related to several time points before (pre‐), during (in‐), and after (post‐) spaceflight. Changes in serum protein levels between spaceflight and on the ground suggest that abnormalities in bone metabolism are induced in astronauts during spaceflight. Furthermore, changes in the proteomic profile occurring during spaceflight suggest that serum levels of bone metabolism‐related proteins, namely ALPL, COL1A1, SPP1, and POSTN, could serve as highly responsive indicators of bone metabolism status in spaceflight missions. This study will allow us to accelerate research to improve our understanding of the molecular mechanisms of biological adaptations associated with prolonged spaceflight.

DOI： 10.1002/pmic.202300328

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.esmogo.2023.08.006

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.esmorw.2023.100005

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Abstract

Objective

The aim of the present study was to investigate which treatment, neoadjuvant chemoradiotherapy (NAC‐RT) with S‐1 or combination neoadjuvant chemotherapy with gemcitabine and S‐1 (NAC‐GS), is more promising as neoadjuvant treatment (NAT) for resectable pancreatic cancer in terms of effectiveness and safety.

Methods

In the NAC‐RT with S‐1 group, the patients received a total radiation dose of 50.4 Gy in 28 fractions with oral S‐1. In the NAC‐GS group, the patients received intravenous gemcitabine at a dose of 1000 mg/m² with oral S‐1 for two cycles. The primary endpoint was the 2‐year progression‐free survival (PFS) rate. The trial was registered with the UMIN Clinical Trial Registry as UMIN000014894.

Results

From April 2014 to April 2017, a total of 103 patients were enrolled. After exclusion of one patient because of ineligibility, 51 patients were included in the NAC‐RT with S‐1 group, and 51 patients were included in the NAC‐GS group in the intention‐to‐treat analysis. The 2‐year PFS rate was 45.0% (90% confidence interval [CI]: 33.3%–56.0%) in the NAC‐RT with S‐1 group and 54.9% (42.8%–65.5%) in the NAC‐GS group (p = .350). The 2‐year overall survival rate was 66.7% in the NAC‐RT with S‐1 group and 72.4% in the NAC‐GS group (p = .300). Although leukopenia and neutropenia rates were significantly higher in the NAC‐GS group than in the NAC‐RT with S‐1 group (p = .023 and p < .001), other adverse events of NAT and postoperative complications were comparable between the two groups.

Conclusion

Both NAC‐RT with S‐1 and NAC‐GS are considered promising treatments for resectable pancreatic cancer.

DOI： 10.1002/jhbp.1353

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Gravity-dependent physical processes strongly affect the ability of elderly people to maintain musculoskeletal health by reducing muscle atrophy and increasing bone mineral density, thereby increasing quality of life. A need therefore exists to identify molecules in the musculoskeletal system that are responsive to gravitational loading and to establish an objective indicator for the maintenance of healthy musculoskeletal systems. Here, we performed an integrated assessment of the results of soleus muscle proteomic analyses in three model mouse experiments under different gravity environments (hypergravity, hindlimb unloading, and spaceflight). Myl6b, Gpd1, Fbp2, Pvalb, and Actn3 were shown to be gravity-responsive muscle proteins, and alterations in the levels of these proteins indicated changes in muscle fiber type to slow-twitch type due to gravity loading. In addition, immunoblotting and enzyme-linked immunosorbent assays revealed that Pvalb levels in the sera of hindlimb-unloaded mice and osteoporosis patients were higher than in control subjects, suggesting that Pvalb levels might be useful to objectively evaluate soleus muscle atrophy and bone loss.

DOI： 10.1038/s41598-023-42875-8

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Other Link： https://www.nature.com/articles/s41598-023-42875-8

Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Clinical studies often collect longitudinal and time-to-event data for each subject. Joint modeling is a powerful methodology for evaluating the association between these data. The existing models, however, have not sufficiently addressed the problem of missing data, which are commonly encountered in longitudinal studies. In this paper, we introduce a novel joint model with shared random effects for incomplete longitudinal data and time-to-event data. Our proposed joint model consists of three submodels: a linear mixed model for the longitudinal data, a Cox proportional hazard model for the time-to-event data, and a Cox proportional hazard model for the time-to-dropout from the study. By simultaneously estimating the parameters included in these submodels, the biases of estimators are expected to decrease under two missing scenarios. We estimated the proposed model by Bayesian approach, and the performance of our method was evaluated through Monte Carlo simulation studies.

DOI： 10.3390/math10193656

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Language：English   Publishing type：Research paper (scientific journal)  

The COVID-19 pandemic is an unprecedented threat to humanity that has provoked global health concerns. Since the etiopathogenesis of this illness is not fully characterized, the prognostic factors enabling treatment decisions have not been well documented. Accurately predicting the progression of the disease would aid in appropriate patient categorization and thus help determine the best treatment option. Here, we have introduced a proteomic approach utilizing data-independent acquisition mass spectrometry (DIA-MS) to identify the serum proteins that are closely associated with COVID-19 prognosis. Twenty-seven proteins were differentially expressed between severely ill COVID-19 patients with an adverse or favorable prognosis. Ingenuity Pathway Analysis revealed that 15 of the 27 proteins might be regulated by cytokine signaling relevant to interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF), and their differential expression was implicated in the systemic inflammatory response and in cardiovascular disorders. We further evaluated practical predictors of the clinical prognosis of severe COVID-19 patients. Subsequent ELISA assays revealed that CHI3L1 and IGFALS may serve as highly sensitive prognostic markers. Our findings can help formulate a diagnostic approach for accurately identifying COVID-19 patients with severe disease and for providing appropriate treatment based on their predicted prognosis.

DOI： 10.1038/s41598-021-98253-9

PubMed

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Corticosteroids use in coronavirus disease 2019 (COVID-19) is controversial, especially in mild to severe patients who do not require invasive/noninvasive ventilation. Moreover, many factors remain unclear regarding the appropriate use of corticosteroids for COVID-19. In this context, this multicenter, retrospective, propensity score–matched study was launched to evaluate the efficacy of systemic corticosteroid administration for hospitalized patients with COVID-19 ranging in the degree of severity from mild to critically-ill disease. This multicenter, retrospective study enrolled consecutive hospitalized COVID-19 patients diagnosed January–April 2020 across 30 institutions in Japan. Clinical outcomes were compared for COVID-19 patients who received or did not receive corticosteroids, after adjusting for propensity scores. The primary endpoint was the odds ratio (OR) for improvement on a 7-point ordinal score on Day 15. Of 1092 COVID-19 patients analyzed, 118 patients were assigned to either the corticosteroid and non-corticosteroid group, after propensity score matching. At baseline, most patients did not require invasive/noninvasive ventilation (85.6% corticosteroid group vs. 89.8% non-corticosteroid group). The odds of improvement in a 7-point ordinal score on Day 15 was significantly lower for the corticosteroid versus non-corticosteroid group (OR, 0.611; 95% confidence interval [CI], 0.388–0.962; p = 0.034). The time to improvement in radiological findings was significantly shorter in the corticosteroid versus non-corticosteroid group (hazard ratio [HR], 1.758; 95% CI, 1.323–2.337; p < 0.001), regardless of baseline clinical status. The duration of invasive mechanical ventilation was shorter in corticosteroid versus non-corticosteroid group (HR, 1.466; 95% CI, 0.841–2.554; p = 0.177). Of the 106 patients who received methylprednisolone, the duration of invasive mechanical ventilation was significantly shorter in the pulse/semi-pulse versus standard dose group (HR, 2.831; 95% CI, 1.347–5.950; p = 0.006). In conclusion, corticosteroids for hospitalized patients with COVID-19 did not improve clinical status on Day 15, but reduced the time to improvement in radiological findings for all patients regardless of disease severity and also reduced the duration of invasive mechanical ventilation in patients who required intubation.

Trial registration: This study was registered in the University hospital Medical Information Network Clinical Trials Registry on April 21, 2020 (ID: UMIN000040211).

DOI： 10.1038/s41598-021-90246-y

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Other Link： https://www.nature.com/articles/s41598-021-90246-y

Language：English  

Web of Science

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Event date： 2023.5 - 2023.6

Presentation type：Poster presentation  

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Event date： 2022.9

Presentation type：Oral presentation (general)  

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Event date： 2021.7

Presentation type：Poster presentation  

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Event date： 2021.3

Presentation type：Poster presentation  

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Event date： 2020.9

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