Gut microbiota: a potential target for improved cancer therapy.

Drug resistance and toxicity are major challenges observed during cancer treatment. In recent years, gut microbiota has been found to be strongly associated with the efficacy, toxicity, and side effects of chemotherapy, radiotherapy, and immunotherapy. Both preclinical studies and clinical trials have demonstrated the potential of microbiota modulation for cancer treatment. The human gut microbiota has exciting prospects for developing biomarkers to predict the outcome of cancer treatment. Moreover, multiple approaches can alter the gut microbiota composition, including faecal microbiota transplantation (FMT), probiotics, antibiotics (ATB), and diet. We describe the mechanisms by which the gut microbiota influences the efficacy and toxicity of cancer therapy, disease-related biomarkers, and methods to target the gut microbiota to improve outcomes. The purpose of this review is to provide new ideas for optimising cancer therapy by providing up-to-date information on the relationship between gut microbiota and cancer therapy, and hopes to find new targets for cancer treatment from human microbiota.

Prevalence of Venous Thromboembolism in Intensive Care Units: A Meta-Analysis.

OBJECTIVE: Venous thromboembolism (VTE) is a life threating complication in intensive care units (ICUs). This study aimed to pool the prevalence of VTE and examined the risk factors of VTE in intensive care patients worldwide. METHODS: A systematic search in PubMed, EMBASE and Web of Science databases was performed. Studies reported that the data on the prevalence of VTE or relevant information were synthesized using a random-effects model. RESULTS: A total of 42 studies reporting on 27,344 patients were included. The pooled prevalence of VTE was 10.0% (95% CI: 7.0-14.0%). Subgroup and metaregression analyses found that thromboprophylaxis strategy, simplified acute physiology score (SAPS II), age, study quality, sample size, malignancy, sex, spinal cord injury and injury severity score (ISS) moderated the prevalence of VTE in intensive care patients. CONCLUSIONS: The present meta-analysis revealed a high prevalence of VTE in critically ill patients. The risk factors of VTE included thromboprophylaxis strategy, SAPS II, age, malignancy, sex, spinal cord injury and ISS. Therefore, we need to pay more attention to high-risk populations of VTE in intensive care patients.

Extracranial multiorgan metastasis from primary glioblastoma: A case report.

BACKGROUND: Glioblastoma has a high degree of malignancy and poor prognosis. It is common to have in situ recurrence and intracranial metastasis, while extracranial metastasis is rare, and extracranial multiorgan metastasis is extremely rare. We report a case of glioblastoma with extracranial multiorgan metastasis, which will strengthen clinicians' attention to the extracranial metastasis of glioblastoma and its treatment. CASE SUMMARY: A male patient visited our hospital for treatment of dizziness and headache. Magnetic resonance imaging of the brain revealed a space-occupying lesion in the right temporoparietal occipital region. Chest computed tomography and abdominal ultrasound were normal, and no space-occupying lesions were observed in other organs of the body. The patient underwent surgery and diagnosed with glioblastoma. Postoperative concurrent radiotherapy and chemotherapy were completed. During the follow-up, the tumor was found to have metastasized to the scalp and neck, and a second tumor resection was performed. Postoperative follow-up revealed extracranial metastases to multiple extracranial organs including skull, scalp, ribs, spine, liver and lung. His family members refused further treatment, and requested only symptomatic treatment such as pain relief, and the patient died of systemic multiple organ failure. Survival time from diagnosis to death was 13 mo and from extracranial metastasis to death was 6 mo. CONCLUSION: Glioblastoma extracranial metastasis is extremely rare, clinicians should always pay attention to its existence. The mechanism of glioblastoma extracranial metastasis is still unclear, and genetic and molecular studies are required.

Association Between Oral Microbiota and Human Brain Glioma Grade: A Case-Control Study.

Gliomas are the most prevalent form of primary malignant brain tumor, which currently have no effective treatments. Evidence from human studies has indicated that oral microbiota is closely related to cancers; however, whether oral microbiota plays a role in glioma malignancy remains unclear. The present study aimed to investigate the association between oral microbiota and grade of glioma and examine the relationship between malignancy-related oral microbial features and the isocitrate dehydrogenase 1 (IDH1) mutation in glioma. High-grade glioma (HGG; n=23) patients, low-grade glioma (LGG; n=12) patients, and healthy control (HCs; n=24) participants were recruited for this case-control study. Saliva samples were collected and analyzed for 16S ribosomal RNA (rRNA) sequencing. We found that the shift in oral microbiota ß-diversity was associated with high-grade glioma (p=0.01). The phylum Patescibacteria was inversely associated with glioma grade (LGG and HC: p=0.035; HGG and HC: p<0.01). The genera Capnocytophaga (LGG and HC: p=0.043; HGG and HC: p<0.01) and Leptotrichia (LGG and HC: p=0.044; HGG and HC: p<0.01) were inversely associated with glioma grades. The genera Bergeyella and Capnocytophaga were significantly more positively correlated with the IDH1 mutation in gliomas when compared with the IDH1-wild-type group. We further identified five oral microbial features (Capnocytophaga Porphyromonas, Haemophilus, Leptotrichia, and TM7x) that accurately discriminated HGG from LGG (area under the curve [AUC]: 0.63, 95% confidence interval [CI]: 0.44-0.83) and HCs (AUC: 0.79, 95% CI: 0.68-0.92). The functional prediction analysis of oral bacterial communities showed that genes involved in cell adhesion molecules (p<0.001), extracellular matrix molecule-receptor interaction (p<0.001), focal adhesion (p<0.001), and regulation of actin cytoskeleton (p<0.001) were associated with glioma grades, and some microbial gene functions involving lipid metabolism and the adenosine 5'-monophosphate-activated protein kinase signaling pathway were significantly more enriched in IDH1 mutant gliomas than compared with the IDH1-wild-type gliomas. In conclusion, our work revealed oral microbiota features and gene functions that were associated with glioma malignancy and the IDH1 mutation in glioma.

Gut Microbiota: A Potential Target for Cancer Interventions.

The gut microbiota plays a crucial role in many physiological processes in the human body. Dysbiosis can disrupt the intestinal barrier and alter metabolism and immune responses, leading to the development of diseases. Over the past few decades, evidence has accumulated linking changes in the composition of the gut microbiota to dozens of seemingly unrelated conditions, including cancer. Overall, the gut microbiota mainly affects the occurrence and development of cancer by damaging host DNA, forming and maintaining a pro-inflammatory environment, and affecting host immune responses. In addition, the gut microbiota can also affect the efficacy and toxicity of chemotherapy, radiotherapy, and immunotherapy. Scientists attempt to improve the efficacy and decrease the toxicity of these treatment modalities by fine-tuning the gut microbiota. The aim of this review is to assist researchers and clinicians in developing new strategies for the detection and treatment of tumors by providing the latest information on the intestinal microbiome and cancer, as well as exploring potential application prospects and mechanisms of action.

Bone Marrow-Derived Mesenchymal Stem Cells Differentially Affect Glioblastoma Cell Proliferation, Migration, and Invasion: A 2D-DIGE Proteomic Analysis.

Bone marrow-derived mesenchymal stem cells (BM-MSCs) display high tumor tropism and cause indirect effects through the cytokines they secrete. However, the effects of BM-MSCs on the biological behaviors of glioblastoma multiforme remain unclear. In this study, the conditioned medium from BM-MSCs significantly inhibited the proliferation of C6 cells (P < 0.05) but promoted their migration and invasion (P < 0.05). Two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) proteomic analysis revealed 17 proteins differentially expressed in C6 cells exposed to the BM-MSC-conditioned medium including five upregulated proteins and 12 downregulated proteins. Among these, six differentially expressed proteins (Calr, Set, Oat, Npm1, Ddah1, and Tardbp) were closely related to cell proliferation and differentiation, and nine proteins (Pdia6, Sphk1, Anxa4, Vim, Tuba1c, Actr1b, Actn4, Rap2c, and Tpm2) were associated with motility and the cytoskeleton, which may modulate the invasion and migration of tumor cells. Above all, by identifying the differentially expressed proteins using proteomics and bioinformatics analysis, BM-MSCs could be genetically modified to specifically express tumor-suppressive factors when BM-MSCs are to be used as tumor-selective targeting carriers in the future.

Clinical study of preoperative psychological distress and its related factors in the primary caregivers of patients with glioma.

OBJECTIVE: To investigate the preoperative psychological distress in the primary caregivers of glioma patients and its influencing factors and to determine the relationship between preoperative psychological states of glioma patients and their caregivers. METHODS: Using a mixed methods design, the caregivers of patients with malignant glioma were interviewed and completed questionnaires about anxiety/depression and family function during preoperative period. RESULTS: Caregivers of glioma patients had different types of psychological distress before surgery. A total of 46 caregivers (36.5 %) had preoperative psychological depression or anxiety symptom; 30 caregivers (23.8 %) had depression symptoms, 39 caregivers (31.0 %) had anxiety symptoms, and 23 (18.3 %) had both preoperative anxiety and depression symptoms. Female gender was an influential factor for both preoperative depression and anxiety symptoms in caregivers, surgical information was a risk factor for caregivers' preoperative depression symptoms and residence was a risk factor for caregivers' preoperative anxiety symptoms. The preoperative psychological states of patients was positively correlated with the preoperative anxiety and depression symptoms of caregivers. CONCLUSION: The rural female caregivers are more likely to experience psychological distress before surgery, and the preoperative psychological states of patients was positively correlated with the psychological distress in caregivers.

Inflammation and behavioral symptoms in preoperational glioma patients: Is depression, anxiety, and cognitive impairment related to markers of systemic inflammation?

PURPOSE: Behavioral symptoms, including depression, anxiety, and cognitive impairment, are common clinical symptoms of patients with glioma. However, the mechanisms underlying the behavioral symptoms of glioma patients remain unclear. In this study, we explore the correlation between markers of systemic inflammation and preoperational behavioral symptoms in glioma patients. PATIENTS AND METHODS: Patients (n = 71) who had recently undertaken imaging (i.e., CT, MRI) for suspected glioma had a face-to-face interview, completed self-report scales, and provided blood samples. Furthermore, we tested blood samples by a protein chip to select differential inflammatory cytokines and further confirm such differences using liquid-phase chip technology. RESULTS: The prevalence of depression, anxiety, and cognitive impairment in glioma patients prior to surgery in this study was 53.5%, 70.4%, and 32.4%, respectively. The increased levels of IFN-γ were positively correlated with clinical symptoms of depression in the glioma patients. Moreover, increased IL-2 levels were negatively associated with anxiety symptoms (p = .00) and positively correlated with cognitive impairment in glioma patients. CONCLUSION: This study suggests that systemic inflammation is associated with behavioral symptoms in glioma patients. This provides further evidence of the contribution of inflammatory markers to psychological symptoms in the context of physical conditions and lays the foundation for the development of further treatments of the behavioral symptoms in glioma patients.

Myristoylated alanine rich protein kinase C substrate is a potential cancer prognostic factor that regulates cell migration and invasion in glioblastoma.

Myristoylated alanine­rich C­kinase substrate (MARCKS) serves an important role in various pathological processes in several malignancies. However, little is known about the specific role and molecular mechanism of MARCKS in glioblastoma (GBM). In the present study, it was found that the expression of MARCKS was significantly upregulated in GBM, and was associated with a poor clinical outcome in patients with GBM. Knockdown of MARCKS suppressed the migration and invasion of GBM cells in vitro. Western blotting showed that the knockdown of MARCKS reduced the expression of phosphorylated phosphoinositide 3­kinase and protein kinase B, as well as zinc finger protein SNAI1 expression, thereby modulating the expression of its downstream epithelial­mesenchymal transition (EMT)­associated factors, including E­cadherin, vimentin, N­cadherin and ß­catenin in GBM cells. These results indicate that MARCKS functioned in the migration and invasion of GBM, and therefore may provide a potential therapeutic target in GBM therapy.

Cerebral Granuloma Mimicking Malignant Neoplasm in Patient with Seizures 21 Years After Head Trauma.

BACKGROUND: Chronic posttraumatic cerebral granuloma is a rare, delayed complication of traumatic brain injury. Because of its late onset of symptoms and atypical appearance, the correct diagnosis of this rare lesion is difficult. CASE DESCRIPTION: A 49-year-old man presented with seizures, which occurred 21 years after open right forehead trauma. Imaging techniques, such as magnetic resonance imaging and magnetic resonance spectroscopy, which indicated a malignant neoplasm, revealed a mass lesion on the right frontal lobe, invading the dura and partial frontal bone. The patient underwent total removal of the lesion and titanium mesh cranioplasty, simultaneously, due to invasion of the mass lesion into the skull. However, the postoperative histopathologic diagnosis was chronic inflammatory granuloma. At 1-year follow-up, he did not have any discomfort and epilepsy did not recur. CONCLUSIONS: Chronic cerebral granuloma should be considered in the differential diagnosis of a novel or recurrent mass detected in patients with a history of traumatic brain injury or prior surgery. Moreover, the retained foreign bodies in the superficial or nonfunctional area of the brain should be thoroughly examined and removed at the time of injury, particularly in open brain trauma.