Qingfei mixture modulates the immune responses in lung cancer through modulating mTOR signaling and gut microbiota-derived short-chain fatty acids.

Lung cancer ranks among the primary contributors to cancer-related fatalities on a global scale. Multiple research investigations have demonstrated that there exists a dysbiosis within the intestinal bacteria and short-chain fatty acids (SCFAs) is linked with immune responses in lung cancer. Qingfei mixture (QFM) has been widely used in treating lung cancer, yet the active ingredients and roles of the QFM on immune responses by targeting gut microbiota remain to be elucidated. The chemical constituents of QFM were qualitatively examined by UPLC/Q-TOF-MS. Additionally, we evaluated the therapeutic impact of the organic substance QFM on lung cancer, aiming to elucidate its mechanisms for improving the tumor-immune microenvironment. Herein, we constructed a Lewis lung carcinoma (LLC)-bearing mice model with QFM treatment to observe tumor growth and immune cell changes. Then, the feces were collected and a combinatory study using metagenomes, non-targeted metabonomics, and targeted metabonomics of SCFAs was performed. In vitro experiments have been conducted to estimate the roles of acetate and sodium propionate in CD8+ T cells. Furthermore, we treated tumor-bearing mice with QFM, QFM + MHY1485 (an mTOR activator), and QFM + an antibiotic mixture (ABX) to explore the potential therapeutic benefit of regulation of the tumor microenvironment. A total of 96 compounds were obtained from QFM by UPLC/Q-TOF-MS. Besides, the findings demonstrated that QFM exhibited significant efficacy against lung cancer, manifesting in reduced tumor growth and improved immune responses. In investigating its mechanisms, we integrated gut microbiota sequencing and fecal metabolomics, revealing that QFM effectively restored disruptions in gut microbiota and SCFAs in mice with lung cancer. QFM, acetate, or sodium propionate contributed to the up-regulation of IFN-γ, Gzms-B, perforin, IL-17, IL-6, IL-12, TNF-α expressions and decreased HDAC and IL-10 levels in vitro and in vivo. Moreover, MHY1485 and ABX weakened the effects of QFM on immunomodulation. Collectively, these results suggest that QFM may facilitate immune responses in the LLC-bearing mice via regulating the gut microbiota-derived SCFAs at least partially through targeting the mTOR signaling pathway.

The value of endoscopic ultrasonography in defining longitudinal gross target volumes for esophageal squamous carcinoma.

BACKGROUND AND PURPOSE: To investigate the differences between endoscopic ultrasonography (EUS)-based longitudinal gross target volumes (GTV) (GTV(EUS)) and computed tomography (CT)-based longitudinal GTV (GTV(CT)) in diagnosing esophageal squamous carcinoma. METHODS: Thirty-six patients underwent EUS to define the superior and inferior extents of the tumor by using hemoclips. CT-planning scan was performed with the patient in the supine position during the treatment. GTV(CT) and GTV(EUS) were contoured respectively. The respective lengths (L(CT) and L(EUS)) and spatial locations of longitudinal GTV(CT) and longitudinal GTV(EUS) were compared. RESULTS: The mean LCT was 7.8 ± 3.2 cm and the mean L(EUS) was 7.4 ± 2.7 cm. No statistical difference was found between L(CT) and L(EUS) (P > 0.05) with a correlation coefficient of 0.61 (P<0.05). The mean conformal index was 0.79 ± 0.18 with spatial variations found in 71% (24/34) of the patients. CONCLUSIONS: EUS can provide additional information to CT in defining longitudinal GTV in thoracic esophageal squamous cell carcinoma, especially superficial and submucosal carcinomas, which may contribute to the development of better individual treatment regimens.

Comparison of radiotherapeutic management of operated breast cancer in 1999 and in 2006: a sampling survey on the southeast coast of China.

AIMS: To obtain a better understanding of the changes in radiotherapeutic management of breast cancer patients in the more developed areas of China over the past decade. METHODS: Four academic radiation therapy departments located on the Southeast Coast of China were selected for the study. The survey was conducted on female breast cancer patients who received radiotherapy in 1999 and 2006. The questionnaires were designed to determine the purposes of radiotherapy and to address the postoperative radiotherapy techniques used. The data for these two years were analyzed and compared. RESULTS: The percentage of breast-conserving treatment increased from 3% in 1999 to 13% in 2006, but the percentage of patients treated with postmastectomy radiotherapy dropped from 69% in 1999 to 66% in 2006 (P < 0.05). As regards the changes in techniques from 1999 to 2006, the use of special immobilization devices, treatment planning systems, and CT simulations increased from 46% to 80%, 23% to 70%, and 0% to 14%, respectively (P <0.01). From 1999 to 2006, irradiation of the chest wall following mastectomy increased from 67% to 90%, but for internal mammary irradiation it decreased from 76% to 30% and for the axilla, from 69% to 37% (P < 0.01). There were no obvious differences between 1999 and 2006 on the field design, boost treatment on the tumor bed, or dose prescription. CONCLUSIONS: Breast-conserving treatment was performed more frequently in China in 2006 than in 1999, but postmastectomy radiotherapy did not change a great deal and it was still an essential option. Although the international treatment guidelines have been accepted and implemented by physicians in recent years, prompt improvement in the quality of breast cancer radiotherapy is needed.