CD44 is a transmembrane glycoprotein. When the CD44 gene is expressed, its pre-messenger RNA (mRNA) can be alternatively spliced into mature mRNAs that encode several CD44 isoforms. The mRNA assembles with ten standard exons, and the sixth variant exon encodes CD44v6, which engages in a variety of biological processes, including cell growth, apoptosis, migration, and angiogenesis. Mechanistically, CD44v6 interacts with hyaluronic acid (HA) or osteopontin, or it acts as a coreceptor for various cytokines, such as epidermal growth factor, vascular endothelial growth factor, hepatocyte growth factor, and C-X-C motif chemokine 12. In this context, the receptor tyrosine kinase or G protein-coupled receptor-associated signaling pathways, including mitogen-activated protein kinase/extracellular-signal-regulated kinase and phosphoinositide-3-kinase/Akt, are activated. Using these actions, homeostasis or regeneration can be facilitated among normal tissues. However, overexpression of the mature mRNA encoding CD44v6 can induce cancer progression. For example, CD44v6 assists colorectal cancer stem cells in colonization, invasion, and metastasis. Overexpression of CD44v6 predicts poor prognosis in patients with colorectal cancer, as patients with a large number of CD44v6-positive cells in their tumors are generally diagnosed at late stages. Thus, the clinical significance of CD44v6 in colorectal cancer deserves consideration. Preclinical results have indicated satisfactory efficacies of anti-CD44 therapy among several cancers, including prostate cancer, pancreatic cancer, and gastric cancer. Moreover, clinical trials aiming to evaluate the pharmacokinetics, pharmacodynamics, efficacy, and toxicity of a commercialized anti-CD44 monoclonal antibody developed by Roche (RO5429083) have been conducted among patients with CD44-expressing malignant tumors, and a clinical trial focusing on the dose escalation of this antibody is ongoing. Thus, we are hopeful that anti-CD44 therapy will be applied in the treatment of colorectal cancer in the future.

The prognosis of leptomeningeal metastasis (LM) from solid tumors is extremely poor, especially for patients with adverse prognostic factors. In this phase II clinical trial, we evaluated the efficacy and safety of intrathecal chemotherapy (IC) combined with concomitant involved‐field radiotherapy (IF‐RT) for treating LM from solid tumors with adverse prognostic factors. Fifty‐nine patients with LM from various solid tumors were enrolled between May 2010 and December 2014. Concurrent therapy consisted of concomitant IC (methotrexate 12.5–15 mg and dexamethasone 5 mg, weekly) and IF‐RT (whole brain and/or spinal canal RT, 40 Gy/20f). For patients with low Karnofsky performance status (KPS) score and radiotherapy intolerance, induction IC (1–3 times) was given before concurrent therapy. Thirty‐eight patients (64.4%) received subsequent treatments. All patients were followed up at least 6 months after LM diagnosis or until death. Primary endpoint evaluated was clinical response rate. Secondary endpoints were overall survival (OS) and safety. The pathological types included lung cancer (n = 42), breast cancer (n = 11) and others (n = 6). Median KPS score was 40 (range 20–70). Fifty‐one patients (86.4%) completed concurrent therapy. The overall response rate was 86.4% (51/59). OS ranged from 0.4 to 36.7 months (median 6.5 months), and 1‐year‐survival rate was 21.3%. Treatment‐related adverse events mainly included acute meningitis, chronic‐delayed encephalopathy, radiculitis, myelosuppression and mucositis. Twelve patients (20.3%) had grade III–V toxic reactions. We concluded that IC combined with concomitant IF‐RT, with significant efficacy and acceptable toxicity, may be an optimal therapeutic option for treatment of LM from solid tumors with adverse prognostic factors. LM, in which cancer cells spread to membranes enveloping the brain and spinal cord, is a devastating complication of solid cancers. Existing LM therapies center on IC. In this prospective clinical study, the authors combined intrathecal methotrexate with involved‐field radiotherapy in a concomitant regimen, showing that the approach can potentially improve quality of life for patients with adverse prognostic factors. Concurrent radiotherapy‐bolstered IC by contributing to prolonged remission of neurological symptoms and increasing OS. The findings suggest that the concomitant regimen could be an optimal treatment option for LM.

Novel advances in the field of brain imaging have enabled the unprecedented clinical application of various imaging modalities to facilitate disease diagnosis and treatment. Electrical impedance tomography (EIT) is a functional imaging technique that measures the transfer impedances between electrodes on the body surface to estimate the spatial distribution of electrical properties of tissues. EIT offers many advantages over other neuroimaging technologies, which has led to its potential clinical use. This qualitative review provides an overview of the basic principles, algorithms, and system composition of EIT. Recent advances in the field of EIT are discussed in the context of epilepsy, stroke, brain injuries and edema, and other brain diseases. Further, we summarize factors limiting the development of brain EIT and highlight prospects for the field. In epilepsy imaging, there have been advances in EIT imaging depth, from cortical to subcortical regions. In stroke research, a bedside EIT stroke monitoring system has been developed for clinical practice, and data support the role of EIT in multi-modal imaging for diagnosing stroke. Additionally, EIT has been applied to monitor the changes in brain water content associated with cerebral edema, enabling the early identification of brain edema and the evaluation of mannitol dehydration. However, anatomically realistic geometry, inhomogeneity, cranium completeness, anisotropy and skull type, etc., must be considered to improve the accuracy of EIT modeling. Thus, the further establishment of EIT as a mature and routine diagnostic technique will necessitate the accumulation of more supporting evidence.

Objectives: Lung cancer in young adults is a distinct disease with particular socioeconomic implications. This study aimed to clarify the clinicopathological characteristics, best interventions, and outcomes of this distinctive entity.

Leakage and compression of blood vessels may result in deprivation of blood flow to a large number of tumor tissues, which can lead to tumor hypoxia. Hypoxia induces an increase in the expression of hypoxia-inducible factor 1 in tumor cells, which induces angiogenesis in tumors through the high expression of vascular endothelial growth factor, thereby forming a positive feedback vicious circle. Improving hypoxia by normalizing blood vessels and improving radiosensitivity by immunotherapy has emerged as a new application of combined immunotherapy and radiotherapy. Interferon γ produced by CD4 + /CD8 + T cells, induced by immune checkpoint inhibitors, plays an important role in the normalization of blood vessels; tumor-associated eosinophils also play a role in the process of immunotherapy-induced blood vessel normalization. In addition, the reduction in regulatory T cells induced by immune checkpoint inhibitors can increase eosinophil levels, which promotes the further development of vascular normalization mechanisms. This review focuses on the mechanism of immunotherapy to normalize blood vessels, and proposes a good prospect for improving hypoxia. Due to the narrow vascular normalization window of anti-angiogenesis therapy, discovery of the vascular normalization effect of immunotherapy provides a new idea for the combined application of immunotherapy and radiotherapy. The enlarged vascular normalization window and improved hypoxia provide a good opportunity for the subsequent implementation of radiotherapy. The above sorting and analysis may pave the way for a promising strategy for cancer treatment via combined immunotherapy and radiotherapy.

In this study, we examined the characteristics and aimed to increase the knowledge of clinical features of leptomeningeal metastasis (LM). The clinical data, including initial diagnosis and treatment of primary tumor, clinical manifestations, neuroimaging findings, cerebrospinal fluid (CSF) examination, were analyzed. For the patients with adenocarcinoma/breast cancer, the incidence of cranial lesions and cranial nerve paralysis was obviously higher than patients with small cell lung cancer. Whereas, the incidence of involvement of intravertebral canal was obviously lower than that of small cell lung cancer. Patients with adenocarcinoma/breast cancer showed more incidence of leptomeningeal enhancement compared to those with small cell lung cancer. Persistent severe headache was noticed in those with squamous carcinoma, and usually showed absence of abnormally LM-related neuroimaging and CSF cytological findings, which resulted in a challenge in the diagnosis of LM from squamous carcinoma. Patients with different primary tumors showed differential clinical features. Significant differences were observed in clinical features between patients with adenocarcinoma/breast cancer and small cell lung cancer. Our study contributes to the understanding of clinical characteristics of LM, and contributes to improvement of LM diagnosis in clinical practice.