Influence of the additional second neighbor hopping on the spin response in the t-J model

The influence of the additional second neighbor hopping t' on the spin response of the t-J model in the underdoped and optimally doped regimes is studied within the fermion-spin theory. Although the additional second neighbor hopping t' is systematically accompanied with the reduction of the dynamical spin structure factor and susceptibility, the qualitative behavior of the dynamical spin structure factor and susceptibility of the t-t'-J model is the same as in the case of t-J model. The integrated dynamical spin structure factor spectrum is almost t' independent, and the integrated dynamical spin susceptibility still shows the particularly universal behavior as $I(\omega,T)\propto {\rm arctan}[a_{1}\omega/T+a_{3}(\omega/T)^{3}]$.Comment: 12 pages, Latex, Four figures are included, final published version [accepted for publication in Phys. Rev. B (July 1 issue)

MUC1 and MUC16: critical for immune modulation in cancer therapeutics

The Mucin (MUC) family, a range of highly glycosylated macromolecules, is ubiquitously expressed in mammalian epithelial cells. Such molecules are pivotal in establishing protective mucosal barriers, serving as defenses against pathogenic assaults. Intriguingly, the aberrant expression of specific MUC proteins, notably Mucin 1 (MUC1) and Mucin 16 (MUC16), within tumor cells, is intimately associated with oncogenesis, proliferation, and metastasis. This association involves various mechanisms, including cellular proliferation, viability, apoptosis resistance, chemotherapeutic resilience, metabolic shifts, and immune surveillance evasion. Due to their distinctive biological roles and structural features in oncology, MUC proteins have attracted considerable attention as prospective targets and biomarkers in cancer therapy. The current review offers an exhaustive exploration of the roles of MUC1 and MUC16 in the context of cancer biomarkers, elucidating their critical contributions to the mechanisms of cellular signal transduction, regulation of immune responses, and the modulation of the tumor microenvironment. Additionally, the article evaluates the latest advances in therapeutic strategies targeting these mucins, focusing on innovations in immunotherapies and targeted drugs, aiming to enhance customization and accuracy in cancer treatments

The application and research progress of anti-angiogenesis therapy in tumor immunotherapy

Tumor immunotherapy, as the focus of scientific research and clinical tumor treatment in recent years, has received extensive attention. Due to its remarkable curative effect and fewer side effects than traditional treatments, it has significant clinical benefits for the treatment of various advanced cancers and can improve cancer patient survival in the long term. Currently, most patients cannot benefit from immunotherapy, and some patients may experience tumor recurrence and drug resistance even if they achieve remission overcome. Numerous studies have shown that the abnormal angiogenesis state of tumors can lead to immunosuppressive tumor microenvironment, which affects the efficacy of immunotherapy. Actually, to improve the efficacy of immunotherapy, the application of anti-angiogenesis drugs to normalize abnormal tumor vessel has been widely confirmed in basic and clinical research. This review not only discusses the risk factors, mechanisms, and effects of abnormal and normalized tumor angiogenesis state on the immune environment, but summarizes the latest progress of immunotherapy combined with anti-angiogenic therapy. We hope this review provides an applied reference for anti-angiogenesis drugs and synergistic immunotherapy therapy

PRIMA-1Met suppresses colorectal cancer independent of p53 by targeting MEK

This work was supported by Grant No. 81201779 (Hua Xiong) from the National Natural Science Youth Foundation; Grant No. 81502118 (Yanmei Zou) from the National Natural Science Youth Foundation; Grant No. 2014CFB250 (Yanmei Zou) from the Natural Science Foundation of Hubei Province; Grant No. 81372434 (Huihua Xiong) from the National Natural Science Foundation.PRIMA-1Met is the methylated PRIMA-1 (p53 reactivation and induction of massive apoptosis) and could restore tumor suppressor function of mutant p53 and induce p53 dependent apoptosis in cancer cells harboring mutant p53. However, p53 independent activity of PRIMA-1Met remains elusive. Here we reported that PRIMA-1Met attenuated colorectal cancer cell growth irrespective of p53 status. Kinase profiling revealed that mitogen-activated or extracellular signal-related protein kinase (MEK) might be a potential target of PRIMA-1Met. Pull-down binding and ATP competitive assay showed that PRIMA-1Met directly bound MEK in vitro and in cells. Furthermore, the direct binding sites of PRIMA-1Met were explored by using a computational docking model. Treatment of colorectal cancer cells with PRIMA-1Met inhibited p53-independent phosphorylation of MEK, which in turn impaired anchorage-independent cell growth in vitro. Moreover, PRIMA-1Met suppressed colorectal cancer growth in xenograft mouse model by inhibiting MEK1 activity. Taken together, our findings demonstrate a novel p53-independent activity of PRIMA-1Met to inhibit MEK and suppress colorectal cancer growth.Publisher PDFPeer reviewe

Doping and temperature dependence of incommensurate antiferromagnetism in underdoped lanthanum cuprates

The doping, temperature and energy dependence of the dynamical spin structure factors of the underdoped lanthanum cuprates in the normal state is studied within the t-J model using the fermion-spin transformation technique. Incommensurate peaks are found at $[(1\pm\delta)\pi,\pi]$, $[\pi,(1\pm\delta)\pi]$ at relatively low temperatures with $\delta$ linearly increasing with doping at the beginning and then saturating at higher dopings. These peaks broaden and weaken in amplitude with temperature and energy, in good agreement with experiments. The theory also predicts a rotation of these peaks by $\pi/4$ at even higher temperatures, being shifted to $[(1\pm \delta/\sqrt{2})\pi,(1\pm \delta/\sqrt{2})\pi]$.Comment: 11 pages, PDF file, six figures are included, accepted for publication in Physical Review

FGFR2 Promotes Gastric Cancer Progression by Inhibiting the Expression of Thrombospondin4 via PI3K-Akt-Mtor Pathway

Background/Aims: Fibroblast growth factor receptor 2 (FGFR2) has attracted considerable interest as a therapeutic target in gastric cancer (GC). There is growing evidence to suggest that the bioavailability of the potent pro-tumor function of FGFR2 is associated with thrombospondins (TSPs). As a follow-on from our previous study, here we evaluated the potential clinical significance and mechanism of the relationship between FGFR2 and TSP4 in GC. Methods: Expression levels of FGFR2 and TSP4 were detected by immunohistochemistry in GC tissue microarray slides. SGC7901 and MKN28 cell lines were used to confirm the relationship between FGFR2 and TSP4. In vitro cell viability, colony formation, and invasion and migration assays were performed to evaluate the effect of FGFR2-TSP4 axis on tumor cell activities. The mechanism of TSP4 regulated by FGFG2 was explored via small molecular inhibitors in vitro and a xenograft model. Results: FGFR2 was shown to be markedly overexpressed in GC tissues and was correlated with a high risk of lymph node metastasis, late clinical stage, and poor prognosis. Low TSP4 expression was associated with shorter overall survival (OS) and advanced stage in GC patients. Interestingly, correlation analysis indicated that FGFR2 was negatively associated with TSP4. Indeed, in vitro and in vivo experiments suggested FGFR2 activation could downregulate TSP4 expression, which played an important role in the proliferation, invasion and migration of GC cells. We also found involvement of the PI3K-AKT-mTOR pathway in the FGFR2-TSP4 axis. Conclusion: The FGFR2 signal promotes human GC progression through the downregulation of TSP4 via PI3K-AKT-mTOR pathway. Our findings provide a foundation for further investigating promising therapeutic strategies for GC overexpressing FGFR2

Genotypes and haplotypes of the VEGF gene and survival in locally advanced non-small cell lung cancer patients treated with chemoradiotherapy

<p>Abstract</p> <p>Background</p> <p>Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis involving in carcinogenesis, including lung cancer. We hypothesized that <it>VEGF </it>polymorphisms may affect survival outcomes among locally advanced non-small cell lung cancer (LA-NSCLC) patients.</p> <p>Methods</p> <p>We genotyped three potentially functional <it>VEGF </it>variants [-460 T > C (rs833061), -634 G > C (rs2010963), and +936 C > T (rs3025039)] and estimated haplotypes in 124 Caucasian patients with LA-NSCLC treated with definitive radiotherapy. We used Kaplan-Meier log-rank tests, and Cox proportional hazard models to evaluate the association between <it>VEGF </it>variants and overall survival (OS).</p> <p>Results</p> <p>Gender, Karnofsky's performance scores (KPS) and clinical stage seemed to influence the OS. The variant C genotypes were independently associated with significantly improved OS (CT+CC vs. TT: adjusted hazard ratio [HR] = 0.58; 95% confidence interval [CI] = 0.37-0.92, <it>P </it>= 0.022), compared with the <it>VEGF </it>-460 TT genotype.</p> <p>Conclusions</p> <p>Our study suggests that <it>VEGF </it>-460 C genotypes may be associated with a better survival of LA-NSCLC patients after chemoradiotherapy. Large studies are needed to confirm our findings.</p

Differential early diagnosis of benign versus malignant lung cancer using systematic pathway flux analysis of peripheral blood leukocytes

Early diagnosis of lung cancer is critically important to reduce disease severity and improve overall survival. Newer, minimally invasive biopsy procedures often fail to provide adequate specimens for accurate tumor subtyping or staging which is necessary to inform appropriate use of molecular targeted therapies and immune checkpoint inhibitors. Thus newer approaches to diagnosis and staging in early lung cancer are needed. This exploratory pilot study obtained peripheral blood samples from 139 individuals with clinically evident pulmonary nodules (benign and malignant), as well as ten healthy persons. They were divided into three cohorts: original cohort (n = 99), control cohort (n = 10), and validation cohort (n = 40). Average RNAseq sequencing of leukocytes in these samples were conducted. Subsequently, data was integrated into artificial intelligence (AI)-based computational approach with system-wide gene expression technology to develop a rapid, effective, non-invasive immune index for early diagnosis of lung cancer. An immune-related index system, IM-Index, was defined and validated for the diagnostic application. IM-Index was applied to assess the malignancies of pulmonary nodules of 109 participants (original + control cohorts) with high accuracy (AUC: 0.822 [95% CI: 0.75–0.91, p < 0.001]), and to differentiate between phases of cancer immunoediting concept (odds ratio: 1.17 [95% CI: 1.1–1.25, p < 0.001]). The predictive ability of IM-Index was validated in a validation cohort with a AUC: 0.883 (95% CI: 0.73–1.00, p < 0.001). The difference between molecular mechanisms of adenocarcinoma and squamous carcinoma histology was also determined via the IM-Index (OR: 1.2 [95% CI 1.14–1.35, p = 0.019]). In addition, a structural metabolic behavior pattern and signaling property in host immunity were found (bonferroni correction, p = 1.32e − 16). Taken together our findings indicate that this AI-based approach may be used for “Super Early” cancer diagnosis and amend the current immunotherpay for lung cancer