Cancer Medicine最新文献

Introduction

Distant metastasis is the main reason for the poor prognosis of gastric cancer, and anoikis refers to the cell death caused when cells detach from the extracellular matrix or adhere in incorrect locations, playing an important role in the distant metastasis of gastric cancer.

Methods

Download the TCGA-STAD dataset and the anoikis gene set, and filter out the differentially expressed anoikis genes. Perform consensus clustering of gastric cancer samples, and conduct Weighted Gene Correlation Network Analysis (WGCNA), enrichment analysis, and immune infiltration analysis for the expression characteristics of each subtype, while also filtering the genes with differential expression between subtypes. Additionally, through COX survival analysis, identify anoikis genes related to gastric cancer prognosis and establish a nomogram. Finally, validate the differentially expressed gene CYP1B1 in vivo and in vitro through clinical samples, cell culture, and the establishment of an anoikis model.

Results

Three subtypes of gastric cancer with anoikis genes were identified, each exhibiting different expression characteristics, biological pathways, and immune cell infiltration. The abundance of activated NK cells, memory B cells, and M2 macrophages showed significant differences among the three subtypes. We screened four differentially expressed gene sets and five genes (CYP1B1, EQTN, NRXN2, TBC1D3E, TCEAL5) among the three subtypes. Through survival analysis, we identified 33 independent prognostic genes and constructed a nomogram, with calibration curves indicating good consistency. Finally, we selected CYP1B1 for experimental validation, and in vivo and in vitro experiments demonstrated that CYP1B1 is highly expressed in gastric cancer, participates in the resistance to cell death in gastric cancer cells, and promotes the invasion, migration, and tumor progression of gastric cancer cells.

Conclusion

The expression patterns of subtypes based on differentially expressed genes related to anoikis in gastric cancer vary, providing theoretical support for the future of personalized treatment for gastric cancer.

Introduction

Prior research has identified temporal muscle thickness (TMT) as a prognostic marker in glioblastoma. Nonetheless, implementation in daily clinical practice is complicated due to the heterogeneity of previous studies. We performed a multicentric analysis aiming to validate recently proposed sex-specific cutoff values using a homogeneous cohort of newly diagnosed MGMT promoter methylated glioblastoma patients; we included a balanced control cohort for comparison.

Materials and Methods

TMT was measured at baseline using the initial preoperative/postoperative magnetic resonance images (MRIs) and in disease course using the first MRI after radiotherapy. Patients were divided by sex and TMT into “at risk of sarcopenia” or “normal muscle status.” Kaplan–Meier and multivariable Cox regression analysis was used for survival correlation.

Results

In total, n = 126 patients were included (n = 66 treated with CCNU/temozolomide, n = 60 with single-drug temozolomide). Patients with normal muscle mass at baseline had significantly prolonged survival (median overall survival: 44.2 months versus 16.7 months with CCNU/temozolomide, and 29.5 months versus 17.4 months with single-drug temozolomide) compared to those at risk of sarcopenia. In a multivariable Cox regression analysis, normal muscle mass and an initial age at diagnosis of < 50 years emerged as significant prognostic markers. Longitudinally, survival was longest in patients with lack of TMT decline over the disease course.

Discussion

This analysis confirms TMT as an important prognostic marker in glioblastoma in two real-life cohorts. However, in order to establish TMT assessment as a routine marker for patient selection and therapeutic measures, further validation in prospective controlled trials is necessary.

Background

To investigate the changes in retinal oxygen kinetics and hemodynamics in patients with choroidal melanoma (CM) within 2 years before and after iodine-125 plaque radiotherapy (PRT) using a novel noninvasive structure-functional imaging analysis system.

Methods

A novel noninvasive cost-effective imaging analysis system that integrates multimodal structural and functional retinal imaging techniques has been used, which allows rapid acquisition of vascular structural, hemodynamic, and oxygenation metrics using multispectral imaging (MSI) and laser speckle contrast imaging (LSCI) techniques. Follow-ups have been arranged at the time before plaque implantation surgery, and 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months after iodine-125 plaque removal.

Results

CM patients after PRT demonstrated a significant decrease in retinal arterial oxygen concentration (CO₂^a), arterial oxygen saturation (SO₂^a), oxygen utilization (SO₂^av, CO₂^av), and metabolism (oxygen extraction fraction, OEF) over time. However, there was no significant difference in SO₂ and CO₂ compared with healthy controls. Systolic time (Time_sr), acceleration time index (ATI), and resistivity index (RI) gradually increase over time; ATI and RI were significantly higher than those of the healthy controls. At baseline, mean arterial blood flow velocity (BFVa) and mean arterial retinal blood flow (RBFa) in CM eyes were significantly higher than those in the healthy control group. BFVa and RBFa showed a decreasing trend over time after PRT. In addition, some retinal oxygen kinetics and hemodynamic indicators were also correlated with tumor size, patient gender, and age.

Conclusion

CM patients after iodine-125 plaque radiotherapy had significant retinal and vascular changes. Future research should focus on rapidly screening radiation microvascular complications and exploring more timely and effective interventions to protect visual function in CM patients.

Background

Cancer-related cognitive impairment (CRCI) is a frequent and burdensome problem that is still insufficiently understood and managed. We investigated subjective and objective measures of CRCI, as recommended by the International Cancer and Cognition Task Force (ICCTF) in cancer patients prior to systemic or radiation therapy with respect to potential influencing or associated psychosocial, demographic, or lifestyle factors.

Methods

Female patients with breast or gynecological tumors (n = 239, mean age = 55.5, SD = 11.6) prior to any systemic or radiation therapy completed validated subjective (FACT-Cog: perceived cognitive impairment [PCI], perceived cognitive ability [PCA], impact on quality of life [IQoL]) and objective measures of CRCI (Trail Making Test [TMT-A and -B], Controlled Oral Word Association Test [COWA], and Hopkins Verbal Learning Test-Revised [HVLT-R]). Association with cross-sectionally assessed age, body mass index, education, smoking, alcohol intake, sleep problems, social support, anxiety, and pain was investigated using multiple linear regression models.

Results

A quarter (25.1%) of patients showed indication for CRCI based on the PCI score. Subjective and objective CRCI measures showed no or only weak correlations, also when adjusting for age and education (partial Spearman correlations with each other, all |r| ≤ 0.21). Anxiety, sleep problems, and pain were significantly associated with low subjective cognitive function (PCI, PCA, and IQoL). Poor objective cognitive values (TMT, COWA, and HVLT-R) were mainly determined by higher age and lower education.

Conclusions

Cancer-related cognitive impairment is not solely (chemo-)therapy-induced but may be triggered or influenced by anxiety, sleep problems, and pain. Addressing these issues early in the treatment phase could potentially alleviate perceived CRCI. The ICCTF-recommended neuropsychological tests do not adequately capture this CRCI prior to systemic or radiation therapy, but could serve as complementary tools to monitor cognitive changes over time, independent of psychosocial influences.

Background

The 5-year survival rate for patients with testicular germ cell tumors (TC) is excellent. However, these survivors are at an increased risk for metabolic syndrome (MetS), a significant source of morbidity and precursor to cardiovascular disease. This study investigates the incidence of MetS in TC survivors compared to matched controls.

Methods

A retrospective analysis was conducted using the Veterans Affairs national database. The incidence of MetS was compared between 2021 TC survivors and 7595 matched controls. MetS was identified via diagnostic codes and medication use, requiring at least three of five criteria: insulin resistance, dyslipidemia, central obesity, and hypertension. Statistical analysis included chi-squared and t-tests for demographic comparisons, and Cox regression for outcome associations.

Results

TC survivors exhibited a greater prevalence of MetS components than controls, specifically hyperglycemia (28.4%), low HDL levels (59.8%), hypertriglyceridemia (8.0%), and abdominal obesity (27.3%), except for hypertension. Over 5 and 10 years, the cumulative incidence of MetS in TC survivors was 17.0% and 27.8%, compared to 1.9% and 2.8% in controls. Multivariate regression showed an increased incidence of MetS in TC survivors (HR = 19.02, 95% confidence interval [CI]: 16.31–22.19, p < 0.001). Chemotherapy (HR = 1.28, 95% CI: 1.04–1.57, p = 0.017) and increasing age (HR = 1.04, 95% CI: 1.04–1.06, p < 0.001) were associated with a higher risk.

Conclusions

TC survivors have a substantial risk of MetS with a higher occurrence of most MetS components, barring hypertension. Comprehensive metabolic health monitoring is crucial in TC survivorship care. Integrating vigilant screening and preventive strategies can mitigate MetS development in this population.

Background

To date, many types of immune cells have been identified, but their precise role in cancer immunity remains unclear. Understanding the immune responses involved in cancer and the cancer microenvironment is becoming increasingly important for elucidating disease mechanisms. In recent years, the application of intravital imaging in cancer research has provided new insights into the mechanisms of cancer-specific immune events, including innate and adaptive immunity.

Results

In this review, we focus on the emerging role of intravital imaging in cancer research and describe how cancer and immune cells can be observed using intravital imaging in vivo. We also discuss new insights gained by this state-of-the-art technique.

Conclusions

Intravital imaging is a relatively new field of research that offers significant advantages, including the ability to directly capture cell–cell interactions, pathophysiology, and immune cell dynamics in the cancer microenvironment in vivo.

Background

The ageing population, increasing medical costs and a number of newly diagnosed cancer cases among the working population are increasing the financial burden on healthcare systems. The extent of financial toxicity in Slovenian patients has been insufficiently researched, as has its impact on quality of life (QoL).

Methods

To evaluate financial toxicity, the Functional Assessment of Chronic Illness Therapy (COST-FACIT) questionnaire was translated into Slovenian, validated, introduced and compared with the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). Additional questions were incorporated into the questionnaire to further quantify and objectify financial toxicity.

The study was cross-sectional. The statistical analysis was based on descriptive and inferential statistics and exploratory data analysis.

Results

Out of 590 analysed participants, financial toxicity was absent in 57.2% but present at mild to moderate levels in 42.8%. Key risk factors included lower income, age ≤ 65, employment, active oncologic treatment, rural residence and religious affiliation. Post hoc analyses showed higher financial toxicity in those with ≤ 600 EUR monthly income, employed patients and spiritual individuals, while cancer type showed no significant differences. The correlation between financial toxicity and QoL was mild. Objective measures of financial toxicity include direct costs (e.g., transportation, supplements and medical devices) and indirect costs (e.g., loss of income) associated with disease and treatment, which burdened more than 40% of the studied population.

Conclusions

The COST-FACIT proved to be a helpful screening tool for identifying patients at risk, even in a public healthcare system such as the Slovenian system. On average, financial toxicity is low due to the publicly funded financial system covering the treatment and rehabilitation of malignant diseases. The age structure of cancer patients and secure pension income further contribute to this outcome.

Background

Immune checkpoint inhibitors (ICIs) improved survival in patients with locally advanced or metastatic urothelial carcinoma (la/mUC). Patient-reported symptoms in this context were poorly studied. The study aimed to compare symptom severity between patients and clinicians.

Methodology

The secondary analysis of the AMI clinical trial comparing changes in the gut microbiota in patients with la/mUC treated with pembrolizumab was conducted in nine French centers. Secondary endpoints were expected in this prospective study. Patient-Reported Outcome-Common Terminology Criteria for Adverse Events (PRO-CTCAE) and CTCAE were assessed respectively by patients and clinicians before pembrolizumab initiation, and at each treatment visit until treatment cycle 12. Agreement in severity between clinicians and patients for grade ≥ 3 symptoms was calculated with Cohen's kappa coefficient. The toxicity index was generated for CTCAE and PRO-CTCAE to assess discordance in a longitudinal manner. The Wilcoxon test was used to compare clinicians' and patients' toxicity index and symptom severity frequencies.

Results

Thirty-nine patients were included (M/F sex ratio: 2.5) from December 2020 to March 2022. PRO-CTCAE baseline completion rate was 77.5%. Cohen's kappa coefficient ranged from −0.017 (95% confidence interval (CI), [−0.039, 0.005]) for numbness/tingling to 0.161 (95% CI, [0.045, 0.276]) for fatigue. The patient self-rated symptom toxicity index was > 2 for all symptoms compared to ≤ 0.62 (fatigue) when assessed by clinicians in longitudinal reporting of symptom frequency and severity with a p value < 0.001. The three most commonly reported symptoms by patients and clinicians, respectively, were: Fatigue 53.3% versus 23.4%, generalized pain 42.4% versus 16.5%, and insomnia 41.1% versus 9.5%. Symptom frequency reports between clinicians and patients were statistically different (p < 0.009).

Conclusions

Symptom severity assessment showed discordance between patients and physicians. Clinicians reported fewer symptoms and graded them less severely than patients. PROs should be used to accurately reflect patient experience.

Trial Registration

ClinicalTrials.gov identifier: NCT04566029

Purpose

Recent work noted lower overall survival (OS) in American Indian/Alaskan Native (AI/AN) individuals diagnosed with colon cancer compared with non-Hispanic White (NHW) individuals. Rectal cancer demographic profiles at diagnosis and survival outcomes have not been reported. We sought to identify differences in rectal cancer diagnosis and outcomes between AI/AN and White populations.

Methods

White and AI/AN patients aged 18 or older, diagnosed between 2004 and 2020 with rectal adenocarcinoma were identified within the National Cancer Database (NCDB). Unadjusted and adjusted analyses were used to evaluate demographic and clinical standardized differences (stddiff) between AI/AN and White patients. Survival analyses of those diagnosed with locally advanced rectal cancer (Stage II/III) were performed using the Kaplan–Meier methods and multivariate Cox-proportional hazards modeling.

Results

176,341 eligible cases were identified: 0.6% were AI/AN (N = 992) and 99.4% White (N = 175,349). Compared to the White population, AI/AN patients were younger at diagnosis (mean age 59.9 vs. 64.5 years; stddiff = 0.36) and had more advanced stage disease (44.8% vs. 43.7%; stddiff = 0.15). A higher percentage of AI/AN resided in the areas of the lowest median income (35.5% vs. 15.1%; stddiff = 0.62) per zip code, rural (9.9% vs. 2.2%; stddiff = 0.65), and used Medicaid as their primary payor (14.3% vs. 6.2%; stddiff = 0.63). Adjusted analyses suggest the AI/AN group has an increased hazard of death compared with the White population (HR, 1.14; 95% CI, 1.05–1.25; p = 0.003).

Conclusions

AI/AN patients with rectal cancer have a younger age and a more advanced stage at diagnosis. AI/AN race is associated with lower OS compared to White patients in multivariable analyses. Future efforts should focus on increasing colorectal cancer screening and access to treatment for AI/AN populations in an attempt to improve survival outcomes.

Background

Chemotherapy combined with angiogenesis inhibition holds great promise in improving the therapeutic efficacy in cancer treatment. The aim of this study was to explore the effect of exosome blockade on tumor angiogenesis and chemotherapy efficacy.

Methods

Exosomes were extracted by ultracentrifugation, and the effect of exosomes on angiogenesis was evaluated by 4T1 mouse breast cancer cell line and the syngeneic mouse tumor model and immunofluorescence. The endocytosis of exosomes from vascular endothelial cells was evaluated in vitro by co-culture and immunofluorescence assays. Tube formation and CCK-8 assays were used to evaluate the effect of exosomes on angiogenesis in vitro. The effect of exosome blockade on the efficacy of doxorubicin was evaluated by 4T1 mouse breast cancer model, cancer cell-derived exosomes (Exo^4T1), GW4869 and doxorubicin in vivo.

Results

Exo^4T1 can be efficiently endocytosed by vascular endothelial cells both in vitro and in vivo. Within the recipient endothelial cells, Exo^4T1 elicited angiogenesis at least partially via promoting cell proliferation, as the exosomes were carrying cargos with pro-proliferation capacity. Blockade of exosome release through GW4869 significantly inhibited angiogenesis, increased the concentration of doxorubicin within the tumor, and sensitized the tumor to doxorubicin in the murine 4T1 syngeneic model, whereas the therapeutic effects were abrogated when Exo^4T1 was additionally treated. Moreover, we found there was no synergy between GW4869 and pazopanib (PP, a traditional angiogenesis inhibitor).

Conclusions

Together, we here revealed that cancer-derived exosomes promote angiogenesis during cancer progression and GW4869 treatment would sensitize the cancer cells to doxorubicin at least partially via inhibiting angiogenesis.