Reprogramming of Lipid Metabolism Mediates Crosstalk, Remodeling, and Intervention of Microenvironment Components in Breast Cancer.

Due to the unique characteristics of breast cancer initiation sites and significant alterations in tumor metabolism, breast cancer cells rely on lipid metabolic reprogramming to effectively regulate metabolic programs during the disease progression cascade. This adaptation enables them to meet the energy demands required for proliferation, invasion, metastasis, and responses to signaling molecules in the breast cancer microenvironment. In this review, we comprehensively examined the distinctive features of lipid metabolic reprogramming in breast cancer and elucidated the underlying mechanisms driving aberrant behavior of tumor cells. Additionally, we emphasize the potential role and adaptive changes in lipid metabolism within the breast cancer microenvironment, while summarizing recent preclinical studies. Overall, precise control over lipid metabolism rewiring and understanding of plasticity within the breast cancer microenvironment hold promising implications for developing targeted treatment strategies against this disease. Therefore, interventions targeting the lipid metabolism in breast cancer may facilitate innovative advancements in clinical applications.

Microenvironmental regulation in tumor progression: Interactions between cancer-associated fibroblasts and immune cells.

The tumor microenvironment (TME), the "soil" on which tumor cells grow, has an important role in regulating the proliferation and metastasis of tumor cells as well as their response to treatment. Cancer-associated fibroblasts (CAFs), as the most abundant stromal cells of the TME, can not only directly alter the immunosuppressive effect of the TME through their own metabolism, but also influence the aggregation and function of immune cells by secreting a large number of cytokines and chemokines, reducing the body's immune surveillance of tumor cells and making them more prone to immune escape. Our study provides a comprehensive review of fibroblast chemotaxis, malignant transformation, metabolic characteristics, and interactions with immune cells. In addition, the current small molecule drugs targeting CAFs have been summarized, including both natural small molecules and targeted drugs for current clinical therapeutic applications. A complete review of the role of fibroblasts in TME from an immune perspective is presented, which has important implications in improving the efficiency of immunotherapy by targeting fibroblasts.

Natural compounds: Wnt pathway inhibitors with therapeutic potential in lung cancer.

The Wnt/ß-catenin pathway is abnormally activated in most lung cancer tissues and considered to be an accelerator of carcinogenesis and lung cancer progression, which is closely related to increased morbidity rates, malignant progression, and treatment resistance. Although targeting the canonical Wnt/ß-catenin pathway shows significant potential for lung cancer therapy, it still faces challenges owing to its complexity, tumor heterogeneity and wide physiological activity. Therefore, it is necessary to elucidate the role of the abnormal activation of the Wnt/ß-catenin pathway in lung cancer progression. Moreover, Wnt inhibitors used in lung cancer clinical trials are expected to break existing therapeutic patterns, although their adverse effects limit the treatment window. This is the first study to summarize the research progress on various compounds, including natural products and derivatives, that target the canonical Wnt pathway in lung cancer to develop safer and more targeted drugs or alternatives. Various natural products have been found to inhibit Wnt/ß-catenin in various ways, such as through upstream and downstream intervention pathways, and have shown encouraging preclinical anti-tumor efficacy. Their diversity and low toxicity make them a popular research topic, laying the foundation for further combination therapies and drug development.

Pharmacological Effects of Polyphenol Phytochemicals on the JAK-STAT Signaling Pathway.

The JAK-STAT signaling pathway is a common pathway of many cytokine signal transductions, closely related to cell proliferation, apoptosis, differentiation, and inflammatory response. It is essential for inhibiting the inflammatory response, initiating innate immunity, and coordinating adaptive immune mechanisms. Owing to the nature of this pathway and its potential cross-epitopes with multiple alternative pathways, the long-term efficacy of monotherapy-based adaptive targeting therapy is limited, and the majority of drugs targeting STATs are still in the preclinical phase. Meanwhile, curcumin, quercetin, and several kinds of plant polyphenol chemicals play roles in multiple sites of the JAK-STAT pathway to suppress abnormal activation. Polyphenol compounds have shown remarkable effects by acting on the JAK-STAT pathway in anti-inflammatory, antitumor, and cardiovascular disease control. This review summarizes the pharmacological effects of more than 20 kinds of phytochemicals on JAK-STAT signaling pathway according to the chemical structure of polyphenolic phytochemicals.

Nanoformulations of Ursolic Acid: A Modern Natural Anticancer Molecule.

Background: Ursolic acid (UA) is a natural pentacyclic triterpene derived from fruit, herb, and other plants. UA can act on molecular targets of various signaling pathways, inhibit the growth of cancer cells, promote cycle stagnation, and induce apoptosis, thereby exerting anticancer activity. However, its poor water-solubility, low intestinal mucosal absorption, and low bioavailability restrict its clinical application. In order to overcome these deficiencies, nanotechnology, has been applied to the pharmacological study of UA. Objective: In this review, we focused on the absorption, distribution, and elimination pharmacokinetics of UA in vivo, as well as on the research progress in various UA nanoformulations, in the hope of providing reference information for the research on the anticancer activity of UA. Methods: Relevant research articles on Pubmed and Web of Science in recent years were searched selectively by using the keywords and subheadings, and were summarized systematically. Key finding: The improvement of the antitumor ability of the UA nanoformulations is mainly due to the improvement of the bioavailability and the enhancement of the targeting ability of the UA molecules. UA nanoformulations can even be combined with computational imaging technology for monitoring or diagnosis. Conclusion: Currently, a variety of UA nanoformulations, such as micelles, liposomes, and nanoparticles, which can increase the solubility and bioactivity of UA, while promoting the accumulation of UA in tumor tissues, have been prepared. Although the research of UA in the nanofield has made great progress, there is still a long way to go before the clinical application of UA nanoformulations.

Predictors of long-term survival following postoperative radiochemotherapy for pathologically confirmed suprasellar germ cell tumors.

The aim of this study was to evaluate the predictors of long-term survival following postoperative therapy for suprasellar germ cell tumors (GCTs). A total of 23 patients with pathologically confirmed suprasellar GCTs were reviewed between April, 1987 and October, 2008. The predictors were identified with a univariate Cox proportional hazards model and the results were used to group patients according to outcome. The overall survival (OS) and progression-free survival (PFS) rates for the good- and poor-prognosis two groups were estimated with Kaplan-Meier analysis, with log-rank tests used to assess differences between the groups. The OS rate for all patients was 82.6% at 5 and 72.9% at 10 years. Lesion size (2-4 vs. >4 cm) and pathological type (pure germinoma vs. mixed GCT) were the only significant predictors of OS (P<0.05). The OS rate for the good-prognosis group was 92.9% at both 5 and 10 years, whereas the corresponding rates for the poor-prognosis group were 66.7 and 40.0%, respectively (P=0.020). The PFS rate for the good-prognosis group was 92.9% at 5 and 85.7% at 10 years, whereas the corresponding PFS rates for the poor-prognosis group were 44.4 and 33.3%, respectively (P=0.007). Lesion size and histology predicted outcome following postoperative therapy for suprasellar GCT. Therefore, pathological diagnosis is recommended whenever possible, as histology may dictate the choice of treatment.

[Clinical analysis of 45 patients with intracranial germinoma treated by radiotherapy].

OBJECTIVE: To report the prospective efficacy of 45 patients intracranial germinoma treated by radiotherapy and discuss its treatment. METHODS: From February 1998 to October 2007, a total of 45 intracranial germinoma patients were performed radiotherapy, including 15 combined chemotherapy in the Department of Oncology. Of them 23 were pathologically diagnosed while 22 cases were clinical diagnosed. Life table method showed the 5-year and 10-year survival rate. RESULTS: Forty patients were followed-up. Most symptoms of the patients were significantly reduced or disappeared completely. The 5-year and 10-year survival rate of all patients were 84% and 74%. CONCLUSION: Radiotherapy is the main treatment for intracranial germinoma. Craniospinal irradiation, whole brain irradiation and partial brain irradiation are the main treatments. Radiotherapy combined with chemotherapy, which can reduce the radiation range and dose will be the trend.

[Effect of CDK2-AP1 gene over-expression on proliferation and cell cycle regulation of breast cancer cell line MCF-7].

OBJECTIVE: To over-express cyclin-dependent kinase 2-associated protein 1 (CDK2-AP1) gene, and investigate its effect on the proliferation and cell cycle regulation in breast cancer cell line MCF-7. METHODS: CDK2-AP1 gene coding region was cloned into lentivirus vector. Lentivirus particles were infected into MCF-7 cells to upregulate the expression of CDK2-AP1 gene. The expression level of CDK2-AP1 was detected at both mRNA and protein levels by real-time PCR and Western blot. MTT assay, colony formatting assay, and flow cytometry were performed to detect the change of proliferation and cell cycle in MCF-7 cells. We examined the expression of cell cycle associated genes (CDK2, CDK4, P16Ink4A, and P21Cip1/Waf1) followed by CDK2-AP1 over-expression by Western blot. RESULTS: CDK2-AP1 gene was up-regulated significantly at both mRNA (6.94 folds) and protein level. MTT based growth curve, colony formatting assay and flow cytometry showed that CDK2-AP1 over-expression lentivirus inhibited the proliferation of MCF-7 cells with statistical difference (P<0.05). In addition, with CDK2-AP1 over-expression, MCF-7 cells were arrested in G1 phase accompanied by apoptosis. Western blot showed that the expression level of P21Cip1/Waf1 and P16 Ink4A was upregulated, while the expression level of CDK2 and CDK4, members of the CDK family, was downregulated. CONCLUSION: CDK2-AP1 gene plays a cancer suppressor role in breast cancer. Its function includes inhibiting the proliferation of MCF-7 cells and arresting the cell cycle in G1 phase.

p12(CDK2-AP1) inhibits breast cancer cell proliferation and in vivo tumor growth.

PURPOSE: p12(CDK2-AP1) is a growth suppressor that negatively regulates cyclin-dependent kinase 2 (CDK2) activities and shows to interfere in DNA replication. Here, we aim to elucidate the role of p12(CDK2-AP1) in breast cancer progression. METHODS: Expression of p12(CDK2-AP1) protein was examined in 60 pairs of breast cancer specimens and adjacent non-tumor tissues using immunohistochemistry assay. Loss-of-function and gain-of-function analysis was performed on MCF-7 and MDA-MB-231 breast cancer cells. Routine assays including MTT, colony formation, flow cytometry, and tumorigenesis in nude mice were performed and cell cycle regulators were analyzed. RESULTS: p12(CDK2-AP1) was found to be significantly downregulated in 60 breast cancer tissues compared to corresponding non-tumorous tissues. The proliferation and colony formation ability was inhibited in cells that transduced with p12(CDK2-AP1) over-expression lentivirus, but enhanced in cells that transduced with p12(CDK2-AP1) RNAi lentivirus. p12(CDK2-AP1) over-expression led to G0/G1 phase arrest in the cell cycle and caused expression changes of cell cycle-related genes (CDK2, CDK4, p16(Ink4A), p21(Cip1/Waf1)). Furthermore, p12(CDK2-AP1) over-expression inhibited in vivo tumor growth in immunodeficiency mice, supporting an inhibitory role for p12(CDK2-AP1) in breast cancer development. CONCLUSIONS: As a cell cycle regulator, p12(CDK2-AP1) is involved in the development of breast cancer and maybe a potential therapeutic candidate to suppress tumorigenicity in breast cancer.

[Efficacy and safety of 3-dimensional conformal radiotherapy combined with temozolomide for glioma].

OBJECTIVE: To study the efficacy and safety of 3-dimensional conformal radiotherapy combined with temozolomide (TMZ) for gliomas. METHODS: A total of 78 patients with pathologically confirmed glioma ( from September 2005 to March 2007) were postoperatively divided into 3 groups: a chemotherapy group (n=24), a radiotherapy group (n=25), and a comprehensive therapy group(n=29). The patients received temozolomide alone,3-dimensional conformal radiotherapy alone,3-dimensional conformal radiotherapy combined with temozolomide in the chemotherapy group,the radiotherapy group and the comprehensive therapy group respectively. The survival rate, progression-free survival, overall survival time and adverse reactions were observed. RESULTS: The 3-year survival rate in the comprehensive therapy group was significantly higher than that in the other two groups. The 3-year survival rates were 20.83%, 20.00%, and 41.38% in the chemotherapy group, the radiotherapy group and the comprehensive therapy group respectively. The progression-free survival time was 17.68,17.94, and 23.29 months and the average overall survival time was 20.28, 21.54, and 25.75 months in the chemotherapy group, the radiotherapy group and the comprehensive therapy group, respectively.The adverse reactions were mild and tolerable. CONCLUSION: Three-dimensional conformal radiotherapy combined with temozolomide is more effective for gliomas than the simple 3-dimensional conformal radiotherapy and the temozolomide chemotherapy alone.

[Expression of Ezrin and E-cadherin in nasopharyngeal carcinoma and its significance].

OBJECTIVE: To explore the association of Ezrin and E-cadherin expression with the invasion, metastasis and prognois of nasopharyngeal carcinoma. METHODS: Imunohistochemical SP staining was used to detect the expression of Ezrin and E-cadherin in 42 nasopharyngeal carcinoma and 10 chronic nasopharyngitis specimens. RESULTS: Ezrin protein expression in the nasopharyngeal carcinoma tissues was significantly higher than that in the chronic nasopharyngitis tissues (P<0.05). E-cadherin expression in the nasopharyngeal carcinoma tissues was significantly lower than that in the chronic nasopharyngitis tissues (P<0.05). Expressions of both Ezrin and E-cadherin of nasopharyngeal carcinoma were closely associated with T staging,the cervical lymph node metastases and clinical staging (P<0.05). A negative correlation was found between Ezrin and E-cadherin expression in the nasopharyngeal carcinoma tissues (r=-0.450, P<0.05). Survival analysis showed that the abnormal expression of Ezrin and E-cadhrin, clinical staging and the cervical lymph node metastases were associated with the survival rate of patients with nasopharyngeal carcinoma. CONCLUSION: A negative correlation is found between Ezrin and E-cadherin expression in the nasopharyngeal carcinoma tissues. Ezrin and E-cadherin are closely related to clinical staging and the cervical lymph node metastases of nasopharyngeal carcinoma,suggesting that they may be important tumor markers for nasopharyngeal carcinoma. Combined detection of the expressions of Ezrin and E-cadherin is helpful for clinical doctors to determine the prognosis of patients with nasopharyngeal carcinoma.