Folic acid-mediated hollow Mn 3 O 4 nanocomposites for in vivo MRI/FLI monitoring the metastasis of gastric cancer.

BACKGROUND: Metastasis is one of the main factors leading to the high mortality rate of gastric cancer. The current monitoring methods are not able to accurately monitor gastric cancer metastasis. METHODS: In this paper, we constructed a new type of hollow Mn 3 O 4 nanocomposites, Mn 3 O 4 @HMSN-Cy7.5-FA, which had a size distribution of approximately 100 nm and showed good stability in different liquid environments. The in vitro magnetic resonance imaging (MRI) results show that the nanocomposite has good response effects to the acidic microenvironment of tumors. The acidic environment can significantly enhance the contrast of T 1 -weighted MRI. The cellular uptake and endocytosis results show that the nanocomposite has good targeting capabilities and exhibits good biosafety, both in vivo and in vitro. In a gastric cancer nude mouse orthotopic metastatic tumor model, with bioluminescence imaging's tumor location information, we realized in vivo MRI/fluorescence imaging (FLI) guided precise monitoring of the gastric cancer orthotopic and metastatic tumors with this nanocomposite. RESULTS: This report demonstrates that Mn 3 O 4 @HMSN-Cy7.5-FA nanocomposites is a promising nano-diagnostic platform for the precision diagnosis and therapy of gastric cancer metastasis in the future. CONCLUSIONS: In vivo MRI/FLI imaging results show that the nanocomposites can achieve accurate monitoring of gastric cancer tumors in situ and metastases. BLI's tumor location information further supports the good accuracy of MRI/FLI dual-modality imaging. The above results show that the MHCF NPs can serve as a good nano-diagnostic platform for precise in vivo monitoring of tumor metastasis. This nanocomposite provides more possibilities for the diagnosis and therapy of gastric cancer metastases.

Magnetic-guided nanocarriers for ionizing/non-ionizing radiation synergistic treatment against triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is a subtype of breast cancer with the worst prognosis. Radiotherapy (RT) is one of the core modalities for the disease; however, the ionizing radiation of RT has severe side effects. The consistent development direction of RT is to achieve better therapeutic effect with lower radiation dose. Studies have demonstrated that synergistic effects can be achieved by combining RT with non-ionizing radiation therapies such as light and magnetic therapy, thereby achieving the goal of dose reduction and efficacy enhancement. METHODS: In this study, we applied FeCo NPs with magneto thermal function and phototherapeutic agent IR-780 to construct an ionizing and non-ionizing radiation synergistic nanoparticle (INS NPs). INS NPs are first subjected to morphology, size, colloidal stability, loading capacity, and photothermal conversion tests. Subsequently, the cell inhibitory and cellular internalization were evaluated using cell lines in vitro. Following comprehensive assessment of the NPs' in vivo biocompatibility, tumor-bearing mouse model was established to evaluate their distribution, targeted delivery, and anti-tumor effects in vivo. RESULTS: INS NPs have a saturation magnetization exceeding 72 emu/g, a hydrodynamic particle size of approximately 40 nm, a negatively charged surface, and good colloidal stability and encapsulation properties. INS NPs maintain the spectral characteristics of IR-780 at 808 nm. Under laser irradiation, the maximum temperature was 92 °C, INS NPs also achieved the effective heat temperature in vivo. Both in vivo and in vitro tests have proven that INS NPs have good biocompatibility. INS NPs remained effective for more than a week after one injection in vivo, and can also be guided and accumulated in tumors through permanent magnets. Later, the results exhibited that under low-dose RT and laser irradiation, the combined intervention group showed significant synergetic effects, and the ROS production rate was much higher than that of the RT and phototherapy-treated groups. In the mice model, 60% of the tumors were completely eradicated. CONCLUSIONS: INS NPs effectively overcome many shortcomings of RT for TNBC and provide experimental basis for the development of novel clinical treatment methods for TNBC.

High-temperature PTT/CDT coordination nanoplatform realizing exacerbated hypoxia for enhancing hypoxia-activated chemotherapy to overcome tumor drug resistance.

BACKGROUND: Hypoxia-activated prodrugs present new opportunities for safe and effective tumor drug resistance therapy due to their high selectivity for hypoxic cells. However, the uneven distribution of oxygen in solid tumor and insufficient hypoxia in the tumor microenvironment greatly limit its therapeutic efficacy. RESULTS: In this paper, a novel AQ4N-Mn(II)@PDA coordination nanoplatform was designed and functionalized with GMBP1 to target drug-resistant tumor cells. Its excellent photothermal conversion efficiency could achieve local high-temperature photothermal therapy in tumors, which could not only effectively exacerbate tumor hypoxia and thus improve the efficacy of hypoxia-activated chemotherapy of AQ4N but also significantly accelerate Mn2+-mediated Fenton-like activity to enhance chemodynamic therapy. Moreover, real-time monitoring of blood oxygen saturation through photoacoustic imaging could reflect the hypoxic status of tumors during treatment. Furthermore, synergistic treatment effectively inhibited tumor growth and improved the survival rate of mice bearing orthotopic drug-resistant tumors. CONCLUSIONS: This study not only provided a new idea for PTT combined with hypoxia-activated chemotherapy and CDT for drug-resistant tumors but also explored a vital theory for real-time monitoring of hypoxia during treatment.

Cobalt Ferrite-Gossypol Coordination Nanoagents with High Photothermal Conversion Efficiency Sensitizing Chemotherapy against Bcl-2 to Induce Tumor Apoptosis.

Gossypol is a chemotherapeutic drug that can inhibit the anti-apoptotic protein Bcl-2, but the existing gossypol-related nanocarriers cannot well solve the problem of chemotherapy resistance. Based on the observation that gossypol becomes black upon Fe3+ coordination, it is hypothesized that encasing gossypol in glyceryl monooleate (GMO) and making it coordinate cobalt ferrite will not only improve its photothermal conversion efficiency (PCE) but also help it enter tumor cells. As the drug loading content and drug encapsulation efficiency of gossypol are 10.67% (w/w) and 96.20%, the PCE of cobalt ferrite rises from 14.71% to 36.00%. The synergistic therapeutic effect finally induces tumor apoptosis with a tumor inhibition rate of 96.56%, which is 2.99 and 1.47 times higher than chemotherapy or photothermal therapy (PTT) alone. PTT generated by the GMO nanocarriers under the irradiation of 808 nm laser can weaken tumor hypoxia, thereby assisting gossypol to inhibit Bcl-2. In addition, the efficacy of nanocarriers is also evaluated through T2 -weighted magnetic resonance imaging. Observations of gossypol-induced apoptosis in tissue slices provide definitive proof of chemotherapy sensitization, indicating that such coordination nanocarriers can be used as an effective preclinical agent to enhance chemotherapy.

Rational design of NIR-II molecule-engineered nanoplatform for preoperative downstaging and imaging-guided surgery of orthotopic hepatic tumor.

Orthotopic advanced hepatic tumor resection without precise location and preoperative downstaging may cause clinical postoperative recurrence and metastasis. Early accurate monitoring and tumor size reduction based on the multifunctional diagnostic-therapeutic integration platform could improve real-time imaging-guided resection efficacy. Here, a Near-Infrared II/Photoacoustic Imaging/Magnetic Resonance Imaging (NIR-II/PAI/MRI) organic nanoplatform IRFEP-FA-DOTA-Gd (IFDG) is developed for integrated diagnosis and treatment of orthotopic hepatic tumor. The IFDG is designed rationally based on the core "S-D-A-D-S" NIR-II probe IRFEP modified with folic acid (FA) for active tumor targeting and Gd-DOTA agent for MR imaging. The IFDG exhibits several advantages, including efficient tumor tissue accumulation, good tumor margin imaging effect, and excellent photothermal conversion effect. Therefore, the IFDG could realize accurate long-term monitoring and photothermal therapy non-invasively of the hepatic tumor to reduce its size. Next, the complete resection of the hepatic tumor in situ lesions could be realized by the intraoperative real-time NIR-II imaging guidance. Notably, the preoperative downstaging strategy is confirmed to lower the postoperative recurrence rate of the liver cancer patients under middle and advanced stage effectively with fewer side effects. Overall, the designed nanoplatform demonstrates great potential as a diagnostic-therapeutic integration platform for precise imaging-guided surgical navigation of orthotopic hepatic tumors with a low recurrence rate after surgery, providing a paradigm for diagnosing and treating the advanced tumors in the future clinical translation application.

Hyaluronic acid functionalized biodegradable mesoporous silica nanocomposites for efficient photothermal and chemotherapy in breast cancer.

Chemotherapy is one of conventional treatment methods for breast cancer, but drug toxicity and side effects have severely limited its clinical applications. Photothermal therapy has emerged as a promising method that, upon combination with chemotherapy, can better treat breast cancer. In this context, a biodegradable mesoporous silica nanoparticle (bMSN NPs) system was developed for loading doxorubicin (DOX) and IR780, to be potentially applied in the treatment of breast cancer. IR780 is encapsulated in the pores of bMSN NPs by hydrophobic adsorption, while DOX is adsorbed on the surface of the bMSN NPs by hyaluronic acid electrostatically, to form the bMID NPs. Transmission electron microscopy, fluorescence spectrum and UV absorption spectrum are used to prove the successful encapsulation of IR780 and the loading of DOX. In vitro experiments have shown bMID NPs present an excellent therapeutic effect on breast cancer cells. In vivo fluorescence imaging results have indicated that bMID NPs can accumulate in tumor sites gradually and achieve in vivo long-term circulation and continuous drug release. Furthermore, bMID NPs have provided obvious antitumor effects in breast cancer mouse models, thus evolving as an efficient platform for breast cancer therapy.

Dual Loading of Nanoparticles with Doxorubicin and Icotinib for the Synergistic Suppression of Non-Small Cell Lung Cancer.

Background: Combination chemotherapy plays an important role in the clinical therapy of non-small cell lung cancer (NSCLC). However, the pharmacokinetic differences between drugs are an insurmountable barrier in traditional treatment. For the synergistic therapy of NSCLC, synergistic nanoparticles (EDS NPs) loaded with both an EGFR inhibitor and doxorubicin (DOX) were designed and prepared. Methods: Erlotinib, apatinib and icotinib were evaluated for optimal combination with DOX in treatment of NSCLC via CCK-8 assay. Then the cationic amphipathic starch (CSaSt) and hyaluronic acid (HA) were applied to coencapsulate DOX and EGFR inhibitor to form the EDS NPs. EDS NPs were evaluated in NSCLC cell lines (A549, NCI-H1975 and PC9) and NSCLC xenograft mouse models. Results: Icotinib was found to be the optimal synergistic drug in combination with DOX in the tested. Subsequently, icotinib and DOX were coencapsulated in the NPs. EDS NPs were roughly spherical with an average size of 65.7±6.2 nm and possessed stable loading and releasing properties. In the in vitro investigation, EDS NPs could efficiently deliver payloads into cells, exhibited cytotoxicity and produced strong anti-migration properties. In vivo hypotoxicity was confirmed by acute toxicity and hemolytic assays. The in vivo distribution showed that EDS NPs could enhance accumulation in tumors and decrease nonspecific accumulation in normal organs. EDS NPs significantly promoted the in vivo synergistic effects of icotinib and DOX in the mouse model. Conclusions: The study suggests that EDS NPs possess noteworthy potential for development as therapeutics for NSCLC clinical chemotherapy.

In Vivo Dual-Modality Fluorescence and Magnetic Resonance Imaging-Guided Lymph Node Mapping with Good Biocompatibility Manganese Oxide Nanoparticles.

Multifunctional manganese oxide nanoparticles (NPs) with impressive enhanced T1 contrast ability show great promise in biomedical diagnosis. Herein, we developed a dual-modality imaging agent system based on polyethylene glycol (PEG)-coated manganese oxide NPs conjugated with organic dye (Cy7.5), which functions as a fluorescence imaging (FI) agent as well as a magnetic resonance imaging (MRI) imaging agent. The formed Mn3O4@PEG-Cy7.5 NPs with the size of ~10 nm exhibit good colloidal stability in different physiological media. Serial FI and MRI studies that non-invasively assessed the bio-distribution pattern and the feasibility for in vivo dual-modality imaging-guided lymph node mapping have been investigated. In addition, histological and biochemical analyses exhibited low toxicity even at a dose of 20 mg/kg in vivo. Since Mn3O4@PEG-Cy7.5 NPs exhibited desirable properties as imaging agents and good biocompatibility, this work offers a robust, safe, and accurate diagnostic platform based on manganese oxide NPs for tumor metastasis diagnosis.

Quality of life in rectal cancer patients after radical surgery: a survey of Chinese patients.

BACKGROUND: We aimed to investigate the impact of sociodemographic and clinical characteristics on health-related quality of life (HRQoL) in disease-free survivors after radical surgery for rectal cancer in a Chinese mainland population. METHODS: We performed a cross-sectional survey from August 2002 to February 2011 by use of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-CR38 questionnaires of 438 patients who underwent curative surgery for rectal cancer. Patients who were followed up for a minimum of 6 months, had no relevant major comorbidities and whose disease had not recurred were asked to complete both questionnaires. The impact of sociodemographic and clinical characteristics on HRQoL were compared by univariate and multivariate regression analyses. RESULTS: In total, 285 patients responded to the survey (response rate, 65.1%). Psychological-related HRQoL variables such as emotional function (P = 0.021) and future perspectives (P = 0.044) were poorer for younger patients than for older patients; and physiological-related HRQoL was reflected by physical function (P = 0.039), which was poorer for older patients than for younger patients. In terms of physiologic function and symptoms concerning HRQoL, such as pain (P = 0.002) and insomnia (P = 0.018), females had lower values than males. Low education and unemployment were associated with a worse HRQoL. HRQoL was worse for patients with stomas compared to those without, especially in psychosocial areas such as role function (P = 0.025), social function (P <0.001) and body image (P = 0.004). Financial HRQoL was worse for younger patients and patients with stoma. CONCLUSIONS: HRQoL aspects and degrees to which they were impaired after curative surgery for rectal cancer were different when compared by many sociodemographic and clinical factors in Chinese mainland patients.

[Evaluation of the rationality of current T staging of gastric cancer with transverse mesocolon invasion].

OBJECTIVE: To evaluate the rationality of T staging of gastric cancer with transverse mesocolon invasion. METHODS: Data of 808 patients with primary gastric cancer undergoing surgical treatment was screened from the Data base of Gastric Cancer of Sun Yat-sen University, from April 1996 to October 2009. According to the information of transverse mesocolon invasion, all cases were divided into groups NOI (T4a stage, non organ invasion, n = 638), NTMI (T4b stage, non transverse mesolon invasion, with organ invasion, n = 126), and TMI (transverse mesocolon invasion, n = 44). The clinicopathological features, surgical procedure and prognosis were compared among the three groups. RESULTS: No significant difference was found in gender, age, lymph node metastasis, hepatic metastasis, tumor's Borrmann type, histological type, differentiation degree, value of serum CEA among the 3 groups (all P > 0.05). In the groups NOI, NTMI and TMI, the ratio of mean tumor diameter ≥ 5 cm was 39.0% (249/638), 61.1% (77/126) and 54.5% (24/44), respectively; the ratio of distal metastasis was 11.9% (76/638), 30.2% (38/126) and 43.2% (19/44), respectively; the ratio of peritoneal metastasis was 8.2% (52/638), 26.2% (33/126) and 38.6% (17/44), respectively; the ratio of TNM IV stage was 25.4% (162/638), 84.7% (107/126) and 93.7% (41/44), respectively; and the ratio of radical resection was 92.0% (587/638), 69.8% (88/126) and 77.3% (34/44), respectively; all with significant differences (P < 0.01), and the results of pairwise comparisons (Bonferroni correction, significant level α = 0.05/3 = 0.0167) showed that these parameters were significantly different between groups NOI and TMI (P < 0.0167), but non-significant between groups NTMI and TMI (P > 0.0167). The median survival time was 42.0, 16.4 and 19.0 months in the groups NOI, NTMI and TMI, respectively (P < 0.01), and the results of pairwise comparison showed that the prognosis were significant different between the groups NOI and TMI (P < 0.01), but non-significant between the groups NTMI and TMI (P > 0.05). In the cases who received radical resection, the median survival time was 47.9, 23.5 and 21.4 months in the groups NOI, NTMI and TMI, respectively (P < 0.01), and the results of pairwise comparison showed that the prognosis was significantly different between the groups NOI and TMI (P < 0.05), but not significant between groups NTMI and TMI (P > 0.05). CONCLUSIONS: The tumor size, distal meatastasis, peritoneal metastasis, TNM stage, surgical procedure and prognosis of gastric cancer with transverse mesocolon invasion are similar to that of T4b gastric cancer, but are significantly different from that of T4a gastric cancer. Gastric cancer with transverse mesocolon invasion should be reclassified as T4b stage.

Prediction method of pharmacokinetic parameters of small molecule drugs based on GCN network model.

CONTEXT: Accurately predicting plasma protein binding rate (PPBR) and oral bioavailability (OBA) helps to better reveal the absorption and distribution of drugs in the human body and subsequent drug design. Although machine learning models have achieved good results in prediction accuracy, they often suffer from insufficient accuracy when dealing with data with irregular topological structures. METHODS: In view of this, this study proposes a pharmacokinetic parameter prediction framework based on graph convolutional networks (GCN), which predicts the PPBR and OBA of small molecule drugs. In the framework, GCN is first used to extract spatial feature information on the topological structure of drug molecules, in order to better learn node features and association information between nodes. Then, based on the principle of drug similarity, this study calculates the similarity between small molecule drugs, selects different thresholds to construct datasets, and establishes a prediction model centered on the GCN algorithm. The experimental results show that compared with traditional machine learning prediction models, the prediction model constructed based on the GCN method performs best on PPBR and OBA datasets with an inter-molecular similarity threshold of 0.25, with MAE of 0.155 and 0.167, respectively. In addition, in order to further improve the accuracy of the prediction model, GCN is combined with other algorithms. Compared to using a single GCN method, the distribution of the predicted values obtained by the combined model is highly consistent with the true values. In summary, this work provides a new method for improving the rate of early drug screening in the future.

Gastric cancer patients with Helicobacter pylori infection have a poor prognosis.

BACKGROUND AND OBJECTIVES: Gastric cancer patients with Helicobacter pylori infection had been reported to have a better prognosis. However, this finding is still controversial. Our research aims to investigate the influence of H. pylori infection on the prognosis of gastric cancer patients who underwent surgery. METHODS: The H. pylori infection status of 162 consecutive gastric cancer patients who underwent surgery was assessed in their tumor samples by immunohistochemical staining. Univariate and multivariable analysis were employed to investigate the potential impact of H. pylori infection status on the gastric cancer-specific survival and relapse-free survival of the patients. RESULTS: The median follow-up period was 35.3 months (range, 1.7-71.9). Gastric cancer-specific survival was 30.2 months (95% CI 24.8-35.6) and relapse-free survival was 28.7 months (23.5-34) in H. pylori positive patients, compared with 39.8 months (34.8-44.7) and 38.1 months (33-43.2), respectively in H. pylori negative patients (P = 0.01 and P = 0.011, respectively. Multivariable analysis showed positive H. pylori infection is an independent prognostic factor for gastric cancer-specific survival (hazard ratio 1.71 [95% CI 1.11-2.66]) and relapse-free survival (hazard ratio 1.68 [95% CI 1.05-2.69]). CONCLUSION: Gastric cancer patients with H. pylori infection have poor gastric cancer-specific survival and relapse-free survival. Our finding suggested that the H. pylori infection could be an indicator for prognosis of gastric cancer patients.

Loss expression of PHLPP1 correlates with lymph node metastasis and exhibits a poor prognosis in patients with gastric cancer.

BACKGROUND: PHLPP1 functions as an antitumor factor in several human cancers, but the expression pattern and clinical significance of PHLPP1 in gastric cancer have yet to be determined. The aim of this study is to assess the expression of PHLPP1 in gastric cancer and its impact on the prognosis of patients with gastric cancer. METHODS: A total of 202 consecutive patients with gastric cancer who had undergone gastrectomy were enrolled in this study. The expressions of PHLPP1 were assessed by immunohistochemistry method. Survival analysis according to PHLPP1 expression was calculated. RESULTS: The positive rates of PHLPP1 protein in primary gastric cancer tissues and metastatic lymph nodes were significantly lower than in normal stomach mucosa tissues (56.9% vs. 96.7%, 38.8% vs. 96.7%, both P < 0.001). The overall survival (OS) time and relapse-free survival (RFS) time in PHLPP1-positive patients were significantly longer than in PHLPP1-negative patients (both P < 0.001). Moreover, PHLPP1 was an independent prognostic factor for OS and RFS of gastric cancer patients (HR 0.55, 95% CI 0.36-0.85, P = 0.007; HR 0.52, 95% CI 0.31-0.87, P = 0.013; respectively). CONCLUSIONS: The loss expression of PHLPP1 was observed in gastric cancer and PHLPP1 is an independent prognostic factor for patients with gastric cancer.

Double-positive expression of high-mobility group box 1 and vascular endothelial growth factor C indicates a poorer prognosis in gastric cancer patients.

BACKGROUND: Although many studies have indicated that high-mobility group box 1 protein (HMGB1) is associated with oncogenesis and a worse prognosis, the prognostic value of HMGB1 in gastric cancer (GC) remains unclear. In the present work, we aimed to evaluate the role of HMGB1 in GC and examined whether aberrant expression of both HMGB1 and vascular endothelial growth factor C (VEGF-C) increased the malignant potential of GC. METHODS: A total of 166 GC patients and 32 normal subjects were enrolled. HMGB1 and VEGF-C expression was detected by tissue microarrays (TMAs) and immunohistochemical staining. The correlation between HMGB1 and VEGF-C expression and their relationships with clinicopathological GC variables were examined. Univariate and multivariate analyses were performed using the Cox proportional hazard model to predict the factors related to the patients' overall survival rates. RESULTS: HMGB1 and VEGF-C expression were observed in 81 (48.80%) and 88 (53.01%) tumors, respectively, significantly higher than the rates among the corresponding controls. In addition, HMGB1 and VEGF-C expression were positively correlated (R2 = 0.972). HMGB1 expression was also closely associated with tumor size, pT stage, nodal status, metastasis status, TNM stage, and poor prognosis. Multivariate survival analysis indicated that patients with HMGB1 and VEGF-C coexpression had the worst prognoses and survival rates (hazard ratio, 2.78; log rank P<0.001). CONCLUSIONS: HMGB1 is commonly expressed in GC. Combined evaluation of HMGB1 and VEGF-C may serve as a valuable independent prognostic factor for GC patients.

[Impact of clinicopathological features and extent of lymph node dissection on the prognosis in early gastric cancer patients].

OBJECTIVE: To explore the impact of clinicopathological features and extent of lymph node dissection on the prognosis in early gastric cancer (EGC) patients. METHODS: A total of 142 EGC cases screened from database of gastric cancer of Sun Yat-sen University, from Aug. 1994 to Jan. 2010, were included in this study. According to the lymph node metastasis status, they were divided into lymph node negative (n = 116) and lymph node positive (n = 26) groups. The clinicopathological features of the two groups and the impact of extent of lymph node dissection on the prognosis were analyzed. RESULTS: There were no significant differences in age, gender, tumor size and location, Borrmann typing, WHO TNM staging, histological typing, and CEA value between the two groups (P > 0.05). The TNM stages in the lymph node positive group were higher than that in the lymph node negative group (P < 0.001). Between the cases who underwent D1 (n = 21) and D2 (n = 121) dissection, there were no significant differences in postoperative hospital days, blood transfusion volume, and operation time (P > 0.05). The median numbers of LN dissected in D1 and D2 cases were 4 (0 to 16) and 20 (12 to 30), with a significant difference (P = 0.000), but the number of positive LN without significant difference (P = 0.502). The postoperative complication rates were 9.5% in the D1 and 3.3% in the D2 dissection groups, without a significant difference (P = 0.128). The median survival time of the lymph node negative and positive groups was 156 vs. 96 months (P = 0.010). In cases who received D2 and D1 lymph node dissection, the median survival time (MST) was 156 vs. 96 months (P = 0.0022). In the lymph node positive group, D2 dissection prolonged survival time significantly than D1 dissection (96 vs. 27months) (P = 0.001). Cox regression analysis showed that the extent of lymph node dissection and LN metastasis were independent prognostic factors for EGC patients. CONCLUSIONS: It is not able to accurately assess the LN metastasis status preoperatively according to the routine clinicopathological features. For the patients with unknown LN metastasis status, D2 dissection should be the first choice. Comparing with D1 dissection, the morbidity of D2 dissection are not increased, but survival time is prolonged.

[Risk factors and prognostic impact of No.12 lymph node metastasis in cases with curable advanced distal gastric cancer].

OBJECTIVE: To explore the risk factors and prognostic impact of duodenal hepatic ligamentous lymph node (No.12 LN) metastasis in cases with curable advanced distal gastric cancer. METHODS: The data of 379 cases with advanced distal gastric cancer undergoing radical resection were screened from the Database of Gastric Cancer Center of Sun Yat-sen University from January 1997 to December 2010. According to No.12 LN metastasis, they were divided into negative (n = 339) and positive (n = 40) groups. Their clinicopathological parameters and surgical regimens were compared. And the risk factors and prognostic impact of No.12 LN metastasis were analyzed. RESULTS: No significant inter-group difference existed in gender, age, infiltration depth or differentiation degree (all P > 0.05). In negative and positive groups, the percent of tumor size ≥ 5 cm was 30.1% (102/339) vs 55.0% (22/40), lymph node metastasis N3 stage 8.3% (28/339) vs 42.5% (17/40), other lymph nodes except for No.12 metastasis 70.2% (238/339) vs 92.5% (37/40), distal metastasis M1 10.9% (37/339) vs 32.5% (13/40), TNM stage IV 18.6% (63/339) vs 65.0% (26/40), infiltration Borrmann type 74.3% (252/339) vs 92.5% (37/40), non-adenocarcinoma 15.9% (54/339) vs 35.0% (14/40) and positive serum-carcinoembryonic antigen (S-CEA) 12.7% (43/339) vs 32.5% (13/40). There were all with significant difference (all P < 0.01). Logistic regression analysis showed tumor size ≥ 5 cm, lymph node (except for No.12) metastasis, distal metastasis and positive S-CEA were independent risk factors of No.12 LN metastasis (OR = 2.144, 3.581, 2.597, 2.552; P = 0.035, 0.042, 0.019, 0.022 respectively). Cox regression analysis showed lymph nodes (except for No.12) and No.12 metastasis, distal metastasis and Borrmann type were independent prognostic factors for all cases. In negative and positive groups, median survival time was 63.0 versus 12.0 months with significant difference (P = 0.000). CONCLUSIONS: For cases with curable advanced distal gastric cancer, No.12 LN metastasis was an independent prognostic factor. No.12 LN should be dissected thoroughly in cases with tumor size ≥ 5 cm, lymph nodes (except No.12) metastasis, distal metastasis and positive S-CEA.

Application of Machine Learning Technology in the Prediction of ADME- Related Pharmacokinetic Parameters.

BACKGROUND: As an important determinant in drug discovery, the accurate analysis and acquisition of pharmacokinetic parameters are very important for the clinical application of drugs. At present, the research and development of new drugs mainly obtain their pharmacokinetic parameters through data analysis, physiological model construction and other methods, but the results are often quite different from the actual situation, needing more manpower and material resources. OBJECTIVE: We mainly discuss the application of machine learning technology in the prediction of pharmacokinetic parameters, which are mainly related to the quantitative study of drug absorption, distribution, metabolism and excretion in the human body, such as bioavailability, clearance, apparent volume of distribution and so on. METHODS: This paper first introduces the pharmacokinetic parameters, the relationship between the quantitative structure-activity relationship model and machine learning, then discusses the application of machine learning technology in different prediction models, and finally discusses the limitations, prospects and future development of the machine learning model in predicting pharmacokinetic parameters. RESULTS: Unlike traditional pharmacokinetic analysis, machine learning technology can use computers and algorithms to speed up the acquisition of pharmacokinetic parameters to varying degrees. It provides a new idea to speed up and shorten the cycle of drug development, and has been successfully applied in drug design and development. CONCLUSION: The use of machine learning technology has great potential in predicting pharmacokinetic parameters. It also provides more choices and opportunities for the design and development of clinical drugs in the future.

Application of radiomics in precision prediction of diagnosis and treatment of gastric cancer.

Gastric cancer is one of the most common malignant tumors. Although some progress has been made in chemotherapy and surgery, it is still one of the highest mortalities in the world. Therefore, early detection, diagnosis and treatment are very important to improve the prognosis of patients. In recent years, with the proposal of the concept of radiomics, it has been gradually applied to histopathological grading, differential diagnosis, therapeutic efficacy and prognosis evaluation of gastric cancer, whose advantage is to comprehensively quantify the tumor phenotype using a large number of quantitative image features, so as to predict and diagnose the lesion area of gastric cancer early. The purpose of this review is to evaluate the research status and progress of radiomics in gastric cancer, and reviewed the workflow and clinical application of radiomics. The 27 original studies on the application of radiomics in gastric cancer were included from web of science database search results from 2017 to 2021, the number of patients included ranged from 30 to 1680, and the models used were based on the combination of radiomics signature and clinical factors. Most of these studies showed positive results, the median radiomics quality score (RQS) for all studies was 36.1%, and the development prospect and challenges of radiomics development were prospected. In general, radiomics has great potential in improving the early prediction and diagnosis of gastric cancer, and provides an unprecedented opportunity for clinical practice to improve the decision support of gastric cancer treatment at a low cost.

Lymphatic endothelial cell-secreted CXCL1 stimulates lymphangiogenesis and metastasis of gastric cancer.

Lymph node metastasis is a significant factor in gastric cancer prognosis. It is well known that cancer cells secrete lymphangiogenic factors, thereby promoting lymphangiogenesis. However, the effects of lymphatic endothelial cell (LEC)-secreted factors on the process of lymphangiogenesis and tumor cell metastasis remain unclear. We established an animal model and successfully isolated LECs from afferent lymph vessels of sentinel lymph nodes (SLNs) in animal models. A microarray analysis was performed to characterize gene expression profile in afferent LECs induced by metastatic cancer cells. There were significant differences in 846 genes between normal LECs and LECs with lymph node metastasis. Among these genes, we found that expression of CXCL1 was upregulated, which was confirmed by quantitative reverse-transcriptase polymerase chain reaction. In a coculture system, gastric cancer cells induced CXCL1 secretion from LECs, which was associated with the NF-κB pathway. CXCL1 stimulated LECs migration and tube formation involving FAK-ERK1/2-RhoA activation and reorganization of F-actin. In human gastric cancer specimens, CXCR2 expression was positively correlated with TNM (Tumor, node, metastasis) stage and lymphatic vessel density. These results suggested that LECs of afferent SLNs had specific expression profiles, which were distinct from those of normal lymphatic vessels and appeared to promote metastasis. The expression pattern described in our study, including CXCL1 in LECs and its receptor CXCR2 in cancer cells, offers a promising therapeutic target for gastric cancer.

[Clinicopathologic features and prognostic analyses of Borrmann type IV gastric cancer].

OBJECTIVE: To compare Borrmann type IV gastric cancer with other types of cancer and explore their clinicopathological features and prognostic factors. METHODS: We retrospectively reviewed the medical records of 893 consecutive advanced gastric cancer patients. They were divided into 2 groups: Borrmann type IV (n = 139) and other macroscopic Borrmann types of cancer (n = 754). Their clinicopathologic characteristics and overall survival data were analyzed. RESULTS: Borrmann type IV gastric cancer was found to be associated with more advanced and unfavorable clinicopathological features. The incidence of preoperative biopsy-negative rate of Borrmann type IV gastric cancer was much higher (15.9%) than other Borrmann types of gastric cancer. The 5-year survival rate of Borrmann type IV cancer patients was 9.9% and it was significantly lower than that of other types. Moreover, the 5-year survival rate was higher in the patients with curative resection (18.7%) (P < 0.05). Stratified analysis revealed that when the tumor TNM stages were of II, III, the survival data of Borrmann type IV cancer were worse than others. Multivariate analyses revealed distant metastasis and curability were independent prognostic factors for Borrmann type IV gastric cancer. CONCLUSIONS: Borrmann type IV carcinoma has poor clinicopathological features and survival rate compared with other types. An early detection and curative resection may improve the prognosis for the patients with Borrmann type IV cancer.