Despite recent advances in chemotherapy for gastrointestinal cancer, a crucial factor related to poor prognosis is reduced tolerance to chemotherapy induced by cancer cachexia. Fish oil (FO)-derived eicosapentaenoic acid (EPA) modulates inflammation in patients with various malignancies; however, the impact of FO-enriched nutrition as a combined modality therapy on clinical outcomes remains controversial. We systemically analysed chronological changes in biochemical and physiological status using bioelectrical impedance analysis in 128 gastrointestinal cancer patients provided with or without FO-enriched nutrition during chemotherapy. Furthermore, we evaluated the clinical significance of FO-enriched nutrition and clarified appropriate patient groups that receive prognostic benefits from FO-enriched nutrition during treatment of gastrointestinal cancer. The control group showed significant up-regulation of serum CRP) levels and no significant difference in both skeletal muscle mass and lean body mass. In contrast, the FO-enriched nutrition group showed no changes in serum CRP concentration and significantly increased skeletal muscle mass and lean body mass over time. Furthermore, high CRP levels significantly correlated with reduced tolerance to chemotherapy, and FO-enriched nutrition improved chemotherapy tolerance and prognosis, particularly in gastrointestinal cancer patients with a modified Glasgow prognostic score (mGPS) of 1 or 2. We conclude that FO-enriched nutrition may improve the prognosis of patients with cancer cachexia and systemic inflammation (i.e., those with a mGPS of 1 or 2).

The combination of re-irradiation and bevacizumab has emerged as a potential therapeutic strategy for patients experiencing their first glioblastoma multiforme (GBM) recurrence. This study aims to assess the effectiveness of the re-irradiation and bevacizumab combination in treating second-progression GBM patients who are resistant to bevacizumab monotherapy. This retrospective study enrolled 64 patients who developed a second progression after single-agent bevacizumab therapy. The patients were divided into two groups: 35 underwent best supportive care (none-ReRT group), and 29 received bevacizumab and re-irradiation (ReRT group). The study measured the overall survival time after bevacizumab failure (OST-BF) and re-irradiation (OST-RT). Statistical tests were used to compare categorical variables, evaluate the difference in recurrence patterns between the two groups, and identify optimal cutoff points for re-irradiation volume. The results of the Kaplan-Meier survival analysis indicated that the re-irradiation (ReRT) group experienced a significantly higher survival rate and longer median survival time than the non-ReRT group. The median OST-BF and OST-RT were 14.5 months and 8.8 months, respectively, for the ReRT group, while the OST-BF for the none-ReRT group was 3.9 months (p < 0.001). The multivariable analysis identified the re-irradiation target volume as a significant factor for OST-RT. Moreover, the re-irradiation target volume exhibited excellent discriminatory ability in the area under the curve (AUC) analysis, with an optimal cutoff point of greater than 27.58 ml. These findings suggest that incorporating re-irradiation with bevacizumab therapy may be a promising treatment strategy for patients with recurrent GBM resistant to bevacizumab monotherapy. The re-irradiation target volume may serve as a valuable selection factor in determining which patients with recurrent GBM are likely to benefit from the combined re-irradiation and bevacizumab treatment modality.

Magnetic stimulation (MS) is a novel approach for treating urinary incontinence (UI), but its applicability remains unclear. This systematic review and meta-analysis were conducted to evaluate the effects of MS treatment on UI. A literature search was performed in EMBASE, PubMed and Cochrane Library (from May 2018 to August 2018), and all randomized control trials (RCTs) published in English were screened to determine whether they met the inclusion criteria. A manual search of the reference lists of the retrieved studies was also performed. Eleven studies involving 612 patients were included in this review. According to the results of the meta-analysis, MS therapy relieved UI symptoms evaluated using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score (mean difference [MD] -3.03, 95% CI -3.27 to -2.79). In addition, the frequency of UI in the MS treatment group was also alleviated compared with sham group (MD -1.42, 95% CI -2.15 to -0.69). Finally, MS treatment improved the quality of life of patients with UI (standardized mean difference [SMD] -1.00, 95% CI -1.24 to -0.76). Our meta-analysis preliminarily indicates that MS treatment is an effective therapeutic modality for patients with UI. Nevertheless, additional large, high quality RCTs with a longer follow-up period that use consistent stimulation methods and analyse comparable outcomes are required to validate the efficacy.

The corneal endothelium maintains corneal transparency; consequently, its dysfunction causes severe vision loss. Tissue engineering-based therapy, as an alternative to conventional donor corneal transplantation, is anticipated to provide a less invasive and more effective therapeutic modality. We conducted a preclinical study for cell-based therapy in a primate model and demonstrated regeneration of the corneal endothelium following injection of cultured monkey corneal endothelial cells (MCECs) or human CECs (HCECs), in combination with a Rho kinase (ROCK) inhibitor, Y-27632, into the anterior chamber. We also evaluated the safety and efficacy of Good Manufacturing Practice (GMP)-grade HCECs, similar to those planned for use as transplant material for human patients in a clinical trial, and we showed that the corneal endothelium was regenerated without adverse effect. We also showed that CEC engraftment is impaired by limited substrate adhesion, which is due to actomyosin contraction induced by dissociation-induced activation of ROCK/MLC signaling. Inclusion of a ROCK inhibitor improves efficiency of engraftment of CECs and enables cell-based therapy for treating corneal endothelial dysfunction as a clinically relevant therapy.

Sonodynamic therapy (SDT) has become a new modality for cancer therapy through activating certain chemical sensitizers by ultrasound (US). Discovery and development of novel sonosensitizers are attracting extensive attentions. Here, we introduce IR-780 iodide, a lipophilic heptamethine dye with a peak optical absorption of 780 nm wavelength, which can function as SDT agents for breast cancer treatment. The in vitro cellular uptake, cell viability, and the generation levels of reactive oxygen species (ROS) were examined by using 4T1 breast cancer cells incubated with various concentrations of IR-780 followed by US irradiation. Our results showed a dose- and time-dependent cellular uptake of IR-780 iodide in 4T1 cancer cells. Significant lower viabilities and more necrotic/apoptotic cells were found when these cancer cells were treated with IR-780 iodide with US irradiation. Further analyzing the generation of ROS demonstrated significant increase of (1)O2 level and H2O2, but not ⋅OH in the SDT-treated cells. The in vivo anti-tumor efficacy of SDT with IR-780 revealed significant tumor growth inhibition of xenografts of 4T1 cancer cells; it was further confirmed by histological analysis and TUNEL staining. Our results strongly suggest that SDT combined with IR-780 may provide a promising strategy for tumor treatment with minimal side effects.

Noninvasive early detection of liver cirrhosis and fibrosis is essential for management and therapy. The aim was to investigated whether a combination of the functional parameter relative enhancement (RE) on Gadoxetic Acid magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI) and the fibrosis parameter T1ρ distinguishes cirrhosis and healthy liver. We analyzed patients with Gd-EOB-DTPA-enhanced MRI and T1ρ mapping. Signal intensity was measured before and after contrast; RE was calculated. T1ρ was measured with circular regions of interest (T1ρ-cROI). A quotient of RE and T1ρ-cROI was calculated: the fibrosis function quotient (FFQ). Cirrhosis was evaluated based on morphology and secondary changes. 213 datasets were included. The difference between cirrhotic and noncirrhotic liver was 51.11 ms vs. 47.56 ms for T1ρ-cROI (p < 0.001), 0.59 vs. 0.70 for RE (p < 0.001), and 89.53 vs. 70.83 for FFQ (p < 0.001). T1ρ-cROI correlated with RE, r = -0.14 (p < 0.05). RE had an AUC of 0.73. The largest AUC had the FFQ with 0.79. The best cutoff value was 48.34 ms for T1ρ-cROI, 0.70 for RE and 78.59 ms for FFQ. In conclusion T1ρ and RE can distinguish between cirrhotic and noncirrhotic liver. The FFQ, which is the combination of the two, improves diagnostic performance.

Ménière's disease (MD) is an inner ear disorder in which the main pathological feature is endolymphatic hydrops (EH). Positive pressure therapy (PPT) using a portable device is now a second-line therapy for intractable MD when initial medical treatment fails. However, it remains unknown whether PPT causes the morphological and functional changes of inner ear in patients with active MD in accordance with reduction of vertigo attacks. In this nonrandomized controlled trial of 52 patients with MD, the volume of EH significantly decreased with reduction of vertigo attacks during 8 months of PPT combined with medications while the volume of that significantly increased with medications alone. There was no difference between Control group (n = 26) and PPT group (n = 26) regarding the vertigo control, however, PPT group achieved a significant functional improvement of vertical semicircular canals. The effect of volume reduction by PPT has been firstly demonstrated and the functional changes of all semicircular canals during PPT have been firstly examined. Morphological and functional changes in the inner ear by administrating local positive pressure are quite different from those caused by medications alone.Clinical trial registration: UMIN-CTR UMIN000041164 (registered on July 20, 2020).

Photoacoustic imaging is a novel hybrid imaging modality combining the high spatial resolution of optical imaging with the high penetration depth of ultrasound imaging. Here, for the first time, we evaluate the efficacy of various photosensitizers that are widely used as photodynamic therapeutic (PDT) agents as photoacoustic contrast agents. Photoacoustic imaging of photosensitizers exhibits advantages over fluorescence imaging, which is prone to photobleaching and autofluorescence interference. In this work, we examined the photoacoustic activity of 5 photosensitizers: zinc phthalocyanine, protoporphyrin IX, 2,4-bis [4-(N,N-dibenzylamino)-2,6-dihydroxyphenyl] squaraine, chlorin e6 and methylene blue in phantoms, among which zinc phthalocyanine showed the highest photoacoustic activity. Subsequently, we evaluated its tumor localization efficiency and biodistribution at multiple time points in a murine model using photoacoustic imaging. We observed that the probe localized at the tumor within 10 minutes post injection, reaching peak accumulation around 1 hour and was cleared within 24 hours, thus, demonstrating the potential of photosensitizers as photoacoustic imaging contrast agents in vivo. This means that the known advantages of photosensitizers such as preferential tumor uptake and PDT efficacy can be combined with photoacoustic imaging capabilities to achieve longitudinal monitoring of cancer progression and therapy in vivo.

When breast cancer patients start to exhibit resistance to hormonal therapy or chemotherapy, the mTOR inhibitor everolimus can be considered as an alternative therapeutic agent. Everolimus can deregulate the PI3K/AKT/mTOR pathway and affect a range of cellular functions. In some patients, the agent does not exhibit the desired efficacy and, even worse, not without the associated side effects. This study assessed the use of immunofluorescence (IF) as a modality to fill this unmet need of predicting the efficacy of everolimus prior to administration. Cell viability and MTT assays based on IF intensities of pho-4EBP1 Thr37/46 and pho-S6K1 Ser424 on breast cancer cells (Hs578T, MCF7, BT474, MDA-MB-231) and patient-derived cell culture from metastatic sites (ABC-82T and ABC-16TX1) were interrogated. Results show that independent pho-4EBP1 Thr37/46 and pho-S6K1 Ser424 IF expressions can classify data into different groups: everolimus sensitive and resistant. The combined IF baseline intensity of these proteins is predictive of the efficacy of everolimus, and their intensities change dynamically when cells are resistant to everolimus. Furthermore, mTOR resistance is not only consequence of the AKT/mTOR pathway but also through the LKB1 or MAPK/ERK pathway. The LKB1 and pho-GSK3β may also be potential predictive markers for everolimus.

5-methylcytosine (m5C) is a post-transcriptional RNA modification identified, m5C readers can specifically identify and bind to m5C. ALYREF and YBX1 as members of m5C readers that have garnered increasing attention in cancer research. However, comprehensive analysis of their molecular functions across pancancer are lacking. Using the TCGA and GTEx databases, we investigated the expression levels and prognostic values of ALYREF and YBX1. Additionally, we assessed the tumor microenvironment, immune checkpoint-related genes, immunomodulators, Tumor Immune Dysfunction and Exclusion (TIDE) score and drug resistance of ALYREF and YBX1. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) analyses were performed to investigate the potential functions associated with m5C readers and coexpressed genes. Aberrant expression of ALYREF and YBX1 was observed and positively associated with prognosis in KIRP, LGG and LIHC. Furthermore, the expression levels of ALYREF and YBX1 were significantly correlated with immune infiltration of the tumor microenvironment and immune-related modulators. Last, our analysis revealed significant correlations between ALYREF, YBX1 and eIFs. Our study provides a substantial understanding of m5C readers and the intricate relationship between ALYREF, YBX1, eIFs, and mRNA dynamics. Through multidimensional analysis of immune infiltration and drug sensitivity/resistance in ALYREF and YBX1, we propose a possibility for combined modality therapy utilizing m5C readers.

Glioblastoma is frequently associated with TP53 mutation, which is linked to a worse prognosis and response to conventional treatments (chemoradiotherapy). Therefore, targeting TP53 is a promising strategy to overcome this poor therapeutic response. Tumor-treating fields (TTFields) are a recently approved treatment for newly diagnosed glioblastoma, which involves direct application of low-intensity, intermediate-frequency alternating electric fields to the tumor, thereby offering a local tumor-killing effect. However, the influence of TP53 mutation status on the effectiveness of TTFields is controversial. Here, we identified the key gene signatures and pathways associated with TTFields in four glioblastoma cell lines varying in TP53 mutation status using gene profiling and functional annotation. Overall, genes associated with the cell cycle, cell death, and immune response were significantly altered by TTFields regardless of TP53 status. TTFields appeared to exert enhanced anti-cancer effects by altering the immune system in the inflammatory environment and regulating cell cycle- and cell death-related genes, but the precise genes influenced vary according to TP53 status. These results should facilitate detailed mechanistic studies on the molecular basis of TTFields to further develop this modality as combination therapy, which can improve the therapeutic effect and minimize side effects of chemoradiotherapy.

Liver biopsy is the reference standard test to differentiate between non-alcoholic steatohepatitis (NASH) and simple steatosis (SS) in non-alcoholic fatty liver disease (NAFLD), but noninvasive diagnostics are warranted. The diagnostic accuracy in NASH using MR imaging modality have not yet been clearly identified. This study was assessed the accuracy of magnetic resonance imaging (MRI) method for diagnosing NASH. Data were extracted from research articles obtained after a literature search from multiple electronic databases. Random-effects meta-analyses were performed to obtain overall effect size of the area under the receiver operating characteristic(ROC) curve, sensitivity, specificity, likelihood ratios(LR), diagnostic odds ratio(DOR) of MRI method in detecting histopathologically-proven SS(or non-NASH) and NASH. Seven studies were analyzed 485 patients, which included 207 SS and 278 NASH. The pooled sensitivity was 87.4% (95% CI, 76.4-95.3) and specificity was 74.3% (95% CI, 62.4-84.6). Pooled positive LR was 2.59 (95% CI, 1.96-3.42) and negative LR was 0.17 (95% CI, 0.07-0.38). DOR was 21.57 (95% CI, 7.27-63.99). The area under the curve of summary ROC was 0.89. Our meta-analysis shows that the MRI-based diagnostic methods are valuable additions in detecting NASH.

Head and Neck Cancer (HNC) is a globally rare cancer that includes a variety of tumors affecting the upper aerodigestive tract. It presents with difficulty breathing or swallowing and is mainly treated with radiation therapy, chemotherapy, or surgery for tumors that have spread locally or throughout the body. Alternatively, exercise can be used during cancer treatment to improve function, including pain relief, increase range of motion and muscle strength, and reduce cancer-related fatigue, thereby enhancing quality of life. Although existing evidence suggests the adjunctive use of exercise in other cancer types, no previous studies have examined the effects on HNC survivors. The aim of this meta-analysis was to quantify the effect of exercise-based rehabilitation on functionality and quality of life in HNC survivors who underwent surgery and/or chemoradiotherapy. A systematic review and meta-analysis were carried out following PRISMA statement and registered in PROSPERO (CRD42023390300). The search was performed in MEDLINE (PubMED), Cochrane Library, CINAHL and Web of Science (WOS) databases from inception to 31st December 2022 using the terms "cancer", "head and neck neoplasms", "exercise", "rehabilitation", "complications", "muscle contraction", "muscle stretching exercises" combining with booleans "AND"/"OR". PEDro scale, Cochrane Risk of Bias Tool and GRADE were used to assess methodological quality, risk of bias and grade of recommendation of included studies respectively. 18 studies (n = 1322) were finally included which 1039 (78.6%) were men and 283 (21.4%) were women. In patients who underwent radio-chemotherapy, overall pain [SMD = - 0.62 [- 4.07, 2.83] CI 95%, Z = 0.35, p = 0.72] and OP [SMD = - 0.07 [- 0.62, 0.48] CI 95%, Z = 0.25, p = 0.81] were slightly reduced with exercise in comparison to controls. Besides, lower limb muscle strength [SMD = - 0.10 [- 1.52, 1.32] CI 95%, Z = 0.14, p = 0.89] and fatigue [SMD = - 0.51 [- 0.97, - 0.057] CI 95%, Z = 2.15, p < 0.01] were also improved in those who receive radio-chemoradiation. In HNC survivors treated with neck dissection surgery, exercise was superior to controls in overall pain [SMD = - 1.04 [- 3.31, 1.23] CI 95%, Z = 0.90, p = 0.37] and, in mid-term, on shoulder pain SMD = - 2.81 [- 7.06, 1.43] CI 95%, Z = 1.76, p = 0.08]. No differences in quality of life were found at any of the follow-up periods. There is evidence of fair to good methodological quality, low to moderate risk of bias, and weak recommendations supporting the use of exercise-based rehabilitation to increase functionality. However, no evidence was found in favor of the use of this modality for improving the quality of life of HNC survivors who underwent chemoradiotherapy or surgery.