International Journal of Cancer最新文献

There is a paucity of literature regarding the effect of anesthetic techniques on antitumor immunity, especially in gall bladder malignancies. We designed a study to compare the effect of propofol-based total intravenous anesthesia and sevoflurane-based general anesthesia—on antitumor immunity, including tumor growth factor-β (TGF-β), T-helper cell profile, and inflammatory markers. A pilot prospective randomized trial was conducted in 64 patients undergoing surgery for gall bladder malignancy under general anesthesia in a tertiary specialty cancer hospital. Adult cancer patients of ASA physical status I-III fulfilling the inclusion criteria were randomized to either group S (sevoflurane-based general anesthesia) or group T (propofol-based total intravenous anesthesia). Preoperative (morning of surgery) and postoperative (24 h and 1 month after surgery) blood samples were obtained. Demographic profile and preoperative parameters were comparable between both groups. There was a statistically significant difference in the postoperative value of TGF-β (higher in group T). There was a statistically significant difference in postoperative interleukin-17A value (indicative of TH17 cells), and it was found to be higher in group S. Propofol-based TIVA increases serum TGF-β levels. At the same time, Sevoflurane modulates T-helper cells-based immunity to increase TH17 cells in patients with gall bladder cancer. Multiple larger studies will be required to validate the results and provide useful recommendations.

Incorporating susceptibility genetic variants of risk factors has been reported to enhance the risk prediction of polygenic risk score (PRS). However, it remains unclear whether this approach is effective for lung cancer. Hence, we aimed to construct a meta polygenic risk score (metaPRS) of lung cancer and assess its prediction of lung cancer risk and implication for risk stratification. Here, a total of 2180 genetic variants were used to develop nine PRSs for lung cancer, three PRSs for different histopathologic subtypes, and 17 PRSs for lung cancer-related risk factors, respectively. These PRSs were then integrated into a metaPRS for lung cancer using the elastic-net Cox regression model in the UK Biobank (N = 442,508). Furthermore, the predictive effects of the metaPRS were assessed in the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial (N = 108,665). The metaPRS was associated with lung cancer risk with a hazard ratio of 1.33 (95% confidence interval: 1.27-1.39) per standard deviation increased. The metaPRS showed the highest C-index (0.580) compared with the previous nine PRSs (C-index: 0.513-0.564) in PLCO. Besides, smokers in the intermediate risk group predicted by the clinical risk model (1.34%-1.51%) with the intermediate-high genetic risk had a 6-year average absolute lung cancer risk that exceeded the clinical risk model threshold (≥1.51%). The addition of metaPRS to the clinical risk model showed continuous net reclassification improvement (continuous NRI = 6.50%) in PLCO. These findings suggest the metaPRS can improve the predictive efficiency of lung cancer compared with the previous PRSs and refine risk stratification for lung cancer.

Burkitt lymphoma (BL) has a tight association with Epstein-Barr virus (EBV), especially in sub-Saharan Africa. While the relationship between BL and EBV is well documented, the relationship between the anti-EBV adaptive immune response, particularly in sub-Saharan African cases, and disease course, has not been substantially investigated. An analysis of T-cell receptor (TCR) complementarity determining region-3 (CDR3) sequences, reported here, from EBV-positive, Ugandan BL tumor samples revealed a correlation between the presence of anti-EBV CDR3s and improved overall survival probabilities. Furthermore, chemical complementarity assessments demonstrated higher complementarity for TCR CDR3s and EBV epitopes in the cases where there had been a detection of the anti-EBV CDR3 AA sequence matches in the BL tumor samples. Overall, the results reported here raise the question of whether EBV targeted immunotherapy would lead to better BL outcomes?

Brainstem gliomas (BSGs) are a class of clinically refractory malignant tumors for which there is no uniform and effective treatment protocol. Ultrasound and radiation can activate hematoporphyrin and produce sonodynamic and radiodynamic effects to kill cancer cells. Therefore, we conducted the first phase I clinical trial of sonodynamic therapy (SDT) combined with radiotherapy (RT) for the treatment of BSGs to verify its safety and efficacy. We conducted a study of SDT combined with RT in 11 patients with BSGs who received SDT and RT after hematoporphyrin administration. Magnetic resonance imaging was performed during this period to assess the tumor, and adverse events were recorded. All adverse events recorded were grade 1-2; no grade 3 or more serious adverse events were observed. Treatment was well tolerated, and no dose-limiting toxicities were observed. There were no treatment-related deaths during the course of treatment. 8 of 11 patients (72.7%) maintained stable disease, 2 (18.2%) achieved partial response, and the tumors were still shrinking as of the last follow-up date. The median progression-free survival (PFS) for patients was 9.2 (95% confidence interval [CI] 6.2-12.2) months, and the median overall survival (OS) was 11.7 (95% CI 9.6-13.8) months. Therefore, SDT combined with RT has a favorable safety and feasibility and shows a preliminary high therapeutic potential.

Measuring pre-diagnostic blood metabolites may help identify novel risk factors for prostate cancer. Using data from 4387 matched case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we investigated the associations of 148 individual metabolites and three previously defined metabolite patterns with prostate cancer risk. Metabolites were measured by liquid chromatography-mass spectrometry. Multivariable-adjusted conditional logistic regression was used to estimate the odds ratio per standard deviation increase in log metabolite concentration and metabolite patterns (OR1SD) for prostate cancer overall, and for advanced, high-grade, aggressive. We corrected for multiple testing using the Benjamini-Hochberg method. Overall, there were no associations between specific metabolites or metabolite patterns and overall, aggressive, or high-grade prostate cancer that passed the multiple testing threshold (padj <0.05). Six phosphatidylcholines (PCs) were inversely associated with advanced prostate cancer diagnosed at or within 10 years of blood collection. metabolite patterns 1 (64 PCs and three hydroxysphingomyelins) and 2 (two acylcarnitines, glutamate, ornithine, and taurine) were also inversely associated with advanced prostate cancer; when stratified by follow-up time, these associations were observed for diagnoses at or within 10 years of recruitment (OR_1SD 0.80, 95% CI 0.66-0.96 and 0.76, 0.59-0.97, respectively) but were weaker after longer follow-up (0.95, 0.82-1.10 and 0.85, 0.67-1.06). Pattern 3 (8 lyso PCs) was associated with prostate cancer death (0.82, 0.68-0.98). Our results suggest that the plasma metabolite profile changes in response to the presence of prostate cancer up to a decade before detection of advanced-stage disease.

Although significant progress in the treatment of breast cancer has been achieved, toxic therapies would not be required if breast cancer could be prevented from developing in the first place. While breast cancer prevention is difficult to study in humans due to long disease latency and stochastic cancer development, transgenic mouse models with 100% incidence and defined mammary tumor onset, provide excellent models for tumor prevention studies. In this study, we used Neu/Erbb2 transgenic mice (MTB-TAN) as a model of human HER2⁺ breast cancer to investigate whether a family of microRNAs, known as the miR-200 family, can prevent mammary tumor development. Overexpression of Neu induced palpable mammary tumors in 100% of the mice within 38 days of Neu overexpression. When the miR-200b/200a/429 cluster was co-overexpressed with Neu in the same mammary epithelial cells (MTB-TANba429 mice), the miR-200b/200a/429 cluster prevented Neu from inducing mammary epithelial hyperplasia and mammary tumor development. RNA sequencing revealed alterations in the extracellular matrix of the mammary gland and a decrease in stromal cells including myoepithelial cells in Neu transgenic mice. Immunohistochemistry for smooth muscle actin confirmed that mammary epithelial cells in control and MTB-TANba429 mice were surrounded by a layer of myoepithelial cells and these myoepithelial cells were lost in MTB-TAN mice with hyperplasia. Thus, we have shown for the first time that elevated expression of miR-200 family members in mammary epithelial cells can completely prevent mammary tumor development in Neu transgenic mice possibly through regulating myoepithelial cells.

Kaposiform hemangioendotheliomas (KHEs) are vascular tumors that are considered borderline or locally aggressive and may lead to lethal outcomes. Traditional therapies, such as surgery and embolization, may be insufficient or technically impossible for patients with KHE. Sirolimus (or rapamycin), a specific inhibitor of mechanistic target of rapamycin, has recently been demonstrated to be very useful in the treatment of KHEs. Here, we highlight recent substantial progress regarding the effects of sirolimus on KHEs and discuss the potential mechanisms of action of sirolimus in treating this disease. The prevention of platelet activation and inflammation, along with antiangiogenic effects, the inhibition of lymphangiogenesis, the attenuation of fibrosis, or a combination of all these effects, may be responsible for the therapeutic effects of sirolimus. In addition, the mechanism of sirolimus resistance in some KHE patients is discussed. Finally, we review the somatic mutations that have recently been identified in KEH lesions, and discuss the potential of novel therapeutic targets based on these further understandings of the cellular and molecular pathogenesis of KHE.

Recent epidemiological studies have increasingly highlighted the antitumor efficacy of IgE owing to the increased malignancy rate in IgE-deficient patients. The purpose of this study, the largest for children, was to determine whether malignant diagnoses in children are associated with IgE deficiency (IgE <2.5 kIU/L). A total of 6821 pediatric patients were reviewed, focusing on patients with IgE below 2.5 kIU/L (n = 599). The causes of IgE testing were evaluated by categorizing them as having cancer, allergies, suspected or diagnosed immunodeficiency, and other conditions. In all but one patient with malignancy, IgE levels were measured after the diagnosis of the disease. Malignancies were observed much more frequently in the low IgE group than in the normal group (10/599, 1.7% and 7/6222, 0.11%; OR = 15.07; 95% CI: 5.72-39.75; p <.0001). According to our analysis, 70% of the patients had leukemia/lymphoma, which is consistent with studies showing that hematologic malignancies are the most frequent cancers linked to IgE deficiency. No increase in the prevalence of cancer was observed in IgE-deficient patients with suspected or diagnosed immunodeficiency. In conclusion, we observed a higher rate of previous malignancy (particularly hematologic cancer) in children with low serum IgE levels. Larger investigations would offer insightful information about the function of low IgE levels in predicting malignancy risk and improving the present diagnostic procedures.

Treatment modifications and contact restrictions were common during the COVID-19 pandemic and can be stressors for mental health. There is a lack of studies assessing pandemic-related risk factors for anxiety and depression of cancer patients and survivors systematically in multifactorial models. A total of 2391 participants, mean age 65.5 years, ≤5 years post-diagnosis of either lung, prostate, breast, colorectal cancer, or leukemia/lymphoma, were recruited in 2021 via the Baden-Württemberg Cancer Registry, Germany. Sociodemographic information, pandemic-related treatment modifications, contact restrictions, and anxiety/depression (Hospital Anxiety and Depression Scale, HADS) were assessed via self-administered questionnaire. Clinical information (diagnosis, stage, and treatment information) was obtained from the cancer registry. Overall, 22% of participants reported oncological care modifications due to COVID-19, mostly in follow-up care and rehabilitation. Modifications of active cancer treatment were reported by 5.8%. Among those, 50.5% had subclinical anxiety and 55.4% subclinical depression (vs. 37.4% and 45.4%, respectively, for unchanged active treatment). Age <60 years, female sex, lung cancer, low income, and contact restrictions to peer support groups or physicians were identified as independent risk factors for anxiety. Risk factors for depression were lung cancer (both sexes), leukemia/lymphoma (females), recurrence or palliative treatment, living alone, low income, and contact restrictions to relatives, physicians, or caregivers. The study demonstrates that changes in active cancer treatment and contact restrictions are associated with impaired mental well-being. The psychological consequences of treatment changes and the importance for cancer patients to maintain regular contact with their physicians should be considered in future responses to threats to public health.