The FGFR2 Variant rs13387042 is Associated With Breast Cancer Risk: A Meta-Analysis and Systematic Review.

OBJECTIVE: The association of FGFR2-rs13387042 polymorphism with breast cancer (BC) susceptibility in women remains inconclusive due to varying reports. In this study, we conducted a meta-analysis to explore the relationship between FGFR2-rs13387042 polymorphism and susceptibility to BC. METHODS: Relevant literature were acquired through searches across multiple databases. Odds ratio (OR) values were pooled to assess the risk of BC for different alleles and genotypes. The heterogeneity among the included literature was evaluated. Sensitivity analysis was used to verify the stability of the results. Egger's linear regression test was used to assess the significance of publication bias of the included literature. RESULTS: A total of 17 publications were included, encompassing 122,607 cases and 175,966 controls. There was significantly increased risk of BC for allele A compared with G (OR = 1.15, 95% CI = 1.14-1.67, P < .001), genotype AA compared with GG (OR = 1.34, 95% CI = 1.29-1.38, P < .001), and genotype GA compared with GG (OR = 1.19, 95% CI = 1.12-1.26, P < .001). Both Egger's test and funnel plot indicated the presence of publication bias. After adjusting potential publication bias by the trim-and-fill method, the comparison of allele A versus G (OR = 1.15, 95% CI = 1.13-1.17, P < .001), genotype AA versus GG (OR = 1.32, 95% CI = 1.28-1.37, P < .001), and genotype GA versus GG (OR = 1.15, 95% CI = 1.09-1.22, P < .001) remained statistically significant. In various subgroups, the allele A showed significantly higher risk of BC upon allele G in estrogen receptor (ER) positive BC, ER negative BC, progesterone receptor (PR) positive BC, PR negative BC, triple-negative BC, pathological grade I BC, grade II BC, and grade III breast cancer. The subsequent sensitivity analysis suggested the above findings stable and reliable. CONCLUSION: In this study, we found that the allele A of the FGFR2-rs13387042 polymorphism is associated with increased risk of developing breast cancer. This study underscores its potential as a genetic marker for personalized risk assessment and targeted interventions.

99mTc-rituximab tracer injection for guiding internal mammary sentinel lymph nodes biopsy in primary breast cancer: A prospective observational study.

Objective: To explore the use of 99mTc-rituximab tracer injection for internal mammary sentinel lymph node (IM-SLN) detection in patients with primary breast cancer. Methods: This prospective observational study enrolled female patients with primary breast cancer between September 2017 and June 2022 at Fujian Provincial Hospital. The participants were divided into the peritumoral group (two subcutaneous injection points on the surface of the tumor), two-site group (injections into the glands at 6 and 12 o'clock around the areola area), and four-site group (injections into the gland at 3, 6, 9, and 12 o'clock around the areola area). The outcomes were the detection rates of the IM-SLNs and axillary sentinel lymph nodes (A-SLNs). Results: Finally, 133 patients were enrolled, including 53 in the peritumoral group, 60 in the two-site group, and 20 in the four-site group. The detection rate of the IM-SLNs in the peritumoral group (9.4% [5/53]) was significantly lower than in the two-site (61.7% [37/60], P<0.001) and four-site (50.0% [10/20], P<0.001) groups. The detection rates of A-SLNs among the three groups were comparable (P=0.436). Conclusion: The two-site or four-site intra-gland injection of 99mTc-rituximab tracer might achieve a higher detection rate of IM-SLNs and a comparable detection rate of A-SLNs compared with the peritumoral method. The location of the primary focus has no impact on the detection rate of the IM-SLNs.

Screening and identification of CNIH4 gene associated with cell proliferation in gastric cancer based on a large-scale CRISPR-Cas9 screening database DepMap.

BACKGROUND: Gastric cancer is a common malignant tumor of digestive tract. The study aimed to identify candidate genes associated with the proliferation and survival of gastric cancer cell through CRISPR-cas9 screening data, which may provide new therapeutic targets for gastric cancer patients. METHODS: Candidate genes related to gastric cancer cell viability by CRISPR-cas9 screening from Depmap and genes differentially expressed between gastric cancer tissues and normal gastric tissues from TCGA were overlapped. WGCNA and KEGG analysis was conducted to performed to identify key pathways and genes. Using CMap, we identified small molecules that might reverse candidate gene expression of gastric cancer. LASSO regression was used to construct a signature to predict overall survival of gastric cancer patients. CCK8 assay was performed to assess the effects of candidate gene on gastric cancer cell proliferation. RESULTS: A total of 710 candidate genes related to gastric cancer cell viability in the DepMap were identified and overlapped with differentially expressed genes in TCGA database, which were enriched in the cell cycle pathway. CMap analysis suggested that molecule drug LY294002 might be a novel choice for gastric cancer treatment. Using Cox univariate analysis and Lasso analysis, we developed a prognostic model including 12 candidate genes, and conducted subgroup analysis and external validation. Moreover, knockdown of the key candidate gene CNIH4 inhibited the proliferation of gastric cancer cells. CONCLUSION: Cell cycle pathway and CNIH4, identified by CRISPR-cas9 screening, were a key pathway and gene that regulate cell viability in gastric cancer. CNIH4 has significant prognostic values and can serve as a new target for gastric cancer patient treatment.

Impact of public health insurance coverage of novel anticancer medication on medical expenditure and patient affordability in a provincial medical centre of China: a propensity score-matching analysis with the quasi-experimental design.

INTRODUCTION: Little is known about the impact of the government's efforts in having novel anticancer medicines covered by the public health insurance system in China. This study targeted the above policy implemented in Fujian province in 2017, analysed the policy impact on the medical expenditure of cancer treatment and patient affordability based on the clinical data of Fujian provincial medical centre. METHODS: The study included 253 human epidermal growth factor receptor 2-positive patients with breast cancer who completed at least one course of trastuzumab treatment extracted from the hospital health information system of the provincial medical centre of Fujian. We adopted the propensity score-matching method to mimic a quasi-experimental design to estimate the impact of the public health insurance coverage policy on all the indicated patients with a before-after comparison of the total breast cancer-associated direct medical expenditures for a standard course of treatment or maintenance treatment and the proportionate patient out-of-pocket (OOP) expenditure based on the real clinical data. RESULTS: We found evidence of an association between the public health insurance coverage of novel breast cancer medication and the reductions of the medical expenditure by US$18661.02 (95% CI 13 836.57 to 28 201.45), and the proportionate patient OOP expenditure by 24% (95% CI0.20 to 0.27). The medical expenditure and the proportionate patient OOP expenditure might be generally reduced. CONCLUSIONS: The coverage of innovative antibreast cancer medicines by the public health insurance was found to be associated with a reduction of the medical expenditure and share of patient OOP expenditure for cancer treatment of the indicated patients. Patients with lower ability-to-pay did not benefit well from the coverage policy. To maximise the welfare of the public health insurance coverage of novel anticancer medication, the study called for strengthened health insurance benefit packages of the rural patient and the patient enrolled in the urban and rural resident health insurance programme, who might have lower ability-to-pay and need more support from the public security system.

Roles of HDAC2, eIF5, and eIF6 in Lung Cancer Tumorigenesis.

OBJECTIVE: The expression levels of histone deacetylase 2 (HDAC2), eukaryotic initiation factor 5 (eIF5), and eukaryotic initiation factor 6 (eIF6), and relationship between HDAC2 and eIF5 or eIF6 in lung cancer tissues were investigated, in order to charify the relationship between HDAC2 and the prognosis of lung cancer patients and its influence on the expression of eIF5 and eIF6. METHODS: The expression of HDAC2, eIF5, and eIF6 in lung cancer tissues was detected by quantitative reverse transcription polymerase chain reaction. The expression correlation between HDAC2 and eIF5 or eIF6 was tested using a t test. The correlation between HDAC2 and eIF5 or eIF6 was analyzed using the TCGA database. The identified cells were constructed with small interfering siRNA and HDAC2 overexpression plasmid. The proliferation and migration ability of the identified cells was investigated by CCK8 and Transwell assays, respectively. RESULTS: HDAC2, eIF5, and eIF6 were overexpressed in lung cancer tissues, and HDAC2 expression level was negatively correlated with the prognosis of lung cancer patients. HDAC2 expression level was positively correlated with eIF5 and eIF6 expression levels. HDAC2 could regulate the expression of eIF5 and eIF6. The regulation of proliferation and invasion of lung cancer cells by HDAC2 depended on eIF5 and eIF6. CONCLUSION: HDAC2, eIF5, and eIF6 were closely related with lung cancer tumorigenesis, which might be potential biological markers and therapeutic targets for lung cancer.

How government health insurance coverage of novel anti-cancer medicines benefited patients in China - a retrospective analysis of hospital clinical data.

BACKGROUND: China started to cover novel medicines for the treatment of major cancers, such as trastuzumab for breast cancer by the government health insurance programs since 2016. Limited data have been published on the use of cancer medications and little is known about how government health insurance coverage of novel anti-cancer medicines benefited patients in the real world. This study aimed to generate evidence to inform the health security authorities to optimize the government health insurance coverage of novel anti-cancer medicines as a more inclusive and equal policy, through which each of the needed patient can get access to the novel anti-cancer medicines regardless of the ability to pay. METHODS: The study targeted one of the government health insurance newly covered novel medicines for breast cancer and the breast cancer patients. The analyses were based on the data collected from one tertiary public hospital in Fujian province of China. We conducted interrupted time series analysis with a segmented regression model and multivariate analyses with a binary logistic regression model to analyze the impact of the government health insurance coverage on medicines utilization and the determinants of patient's medication choice. RESULTS: The average proportion of patients who initiated medication with novel medicines increased from 37.4% before the government health insurance coverage to 69.2% afterwards. Such an increase was observed in all patient sub-groups. The monthly proportion of patients who initiated medication with novel medicines increased sharply by 18.3 % (95 %CI,10.4-34.0 %, p = 0.01) in September 2017, the afterwards trend continuously increased (95 %CI,1.03-3.60, p = 0.02). The critical determinants of patient's medication choice were mostly connected with the patient's health insurance benefits packages. CONCLUSIONS: The government health insurance coverage of novel anti-breast-cancer medicines benefited the patients generally. The utilization of novel medicines such as trastuzumab continuously increased. The insurance coverage benefited well the patients in the high-risk age groups. However, rural patients, patients enrolled in the "resident program", and patients from low-income residential areas and non-local patients benefited less from this policy. Improving the benefits package of the low-income patients and the "resident program" beneficiary would be of considerable significance for a more inclusive and equal health insurance coverage of novel anti-cancer medicines.

Overexpression of c-Ski promotes cell proliferation, invasion and migration of gastric cancer associated fibroblasts.

The present study aimed to investigate the effects of c-Ski on cell proliferation, invasion and migration of gastric cancer associated fibroblasts (CAFs). Expression of c-Ski in gastric cancer (GC) tissues was determined using immunohistochemistry. Both CAFs and non-cancerous gastric fibroblasts (NGFs) were isolated and cultured. c-Ski and Smad3 were over-expressed or knocked down using pcDNA3.0-c-Ski/Smad3 or siRNA, respectively. Cell viability, invasion and migration were measured and expression of c-Ski, α-SMA, and Smad3 in cells was determined using real time quantitative PCR (RT-qPCR) and Western blotting. Expression of c-Ski was significantly higher in both in GC tissues and cell lines, and was the highest in tissues of diffuse type. Both c-Ski and α-SMA were significantly over-expressed in CAFs compared with that in the NGFs. When c-Ski was over-expressed in NGFs, cell viability, cell invasion and migration were all enhanced and expression of Smad3 was downregulated. When c-Ski was inhibited, cell viability, cell invasion, and migration were all suppressed and expression of Smad3 was upregulated. Meanwhile, overexpression of Smad3 significantly reversed the effects of over-expressed c-Ski in NGFs, and knockdown of Smad3 dramatically reversed the effects of si-c-Ski in CAFs. Over-expressed c-Ski could enhance cell viability, promote cell invasion, and migration of GC CAFs, and the effects might be through regulation of Smad3 signaling. This study may give deeper insights for relationship between c-Ski and CAFs, as well as role of c-Ski in cancer development, and also provide some novel research targets for treatment of GC.

[Application of intracorporeal uncut Roux-en-Y anastomosis in digestive tract reconstruction after laparoscopic total gastrectomy].

OBJECTIVE: To explore the safety, feasibility and short-term efficacy of intracavitary uncut Roux-en-Y (URY) anastomosis in digestive tract reconstruction following laparoscopic total gastrectomy (LTG). METHODS: From November 2015 to January 2018, 67 gastric cancer patients underwent intracavitary URY following LTG to reconstruct the digestive tract at Oncological Surgery Department of Fujian Provincial Hospital. There were 41 males and 26 females with age of 50 to 81 (61.9±7.4) years and body mass index (BMI) of (23.4±3.2) kg/m². Among 67 patients, 19 were gastric cardia carcinomas, 33 were gastric body carcinomas, and 15 were gastric fundus carcinomas; tumor size was (3.4±2.3) cm; 22 were Borrmann type I, 15 were type II, 21 were type III, and 19 were type IV; 29 were highly or moderately differentiated adenocarcinoma, 23 were lowly differentiated adenocarcinoma, and 15 were signet-ring cell carcinoma. After conventional laparoscopic D2 radical gastrectomy, the duodenum was closed and dissociated at 2 cm below the pyloric ring using the Echelon-flex endoscopic articulated linear Endo-GIA stapler, and the esophagus was dissociated above the esophagogastric junction (EGJ).URY and digestive tract reconstruction were performed under the direct vision of laparoscope: (1) Side-to-side esophagojejunostomy: An incision of 0.5 cm was made in the left lower edge of the esophageal closed end; jejunum about 25 cm distal away from the Treitz ligament was elevated to the lower end of esophagus; another incision of 0.5 cm was made in the contralateral of mesenteric side; both arms of the linear Endo-GIA stapler were inserted into the windows opened through esophagus and jejunum respectively to complete side-to-side anastomosis. The common opening of esophagus and jejunum was closed to complete esophagojejunostomy, forming the chyme outflow tract. (2) Side-to-side Braun jejunojejunostomy: Incisions of 0.5 cm were made in the proximal jejunum about 10 cm away from the esophagojejunal anastomosis and 35-40 cm away from the contralateral of mesenteric side of distal jejunum respectively for proximal-distal side-to-side jejunojejunostomy. The common opening was closed to form the biliopancreatic duodenal juice outflow tract. (3) Closure of the input loop jejunum in the esophagojejunal anastomosis: The input loop jejunum 2-3 cm away from the esophagojejunal anastomosis was closed using the non-blade linear stapler (ATS45NK), and the biliopancreatic duodenal juice reflux was blocked. Clinical data of these patients were collected for retrospective case series study. Surgical and digestive tract functional recovery, perioperative complications, as well as postoperative nutritional status were observed. Moreover, related indexes, such as anastomosis function and tumor recurrence were evaluated through endoscopic and imaging examinations during postoperative follows-up. RESULTS: All the 67 patients completed the surgery successfully. The mean operative time was (259.4±38.5) minutes, digestive tract reconstruction time was (38.2±13.2) minutes, intraoperative blood loss was (73.4±38.4) ml, and number of harvested lymph node was 36.2±14.2. The mean distance from upper resection margin to upper tumor edge was (3.3±1.2) cm, distance from upper resection margin to dentate line was (1.2±0.7) cm, and 1 case had positive upper incisal margin, which became negative after the second resection. Moreover, the average length of the auxiliary incision was (3.2±0.4) cm. The mean postoperative intestinal exhaust time was (52.8±26.4) hours, time to liquid diet was (64.8±28.8) hours, and postoperative hospital stay was (8.4±2.5) days. The morbidity of postoperative complication was 10.4%(7/67). Among these 7 cases, 4 cases were grade IIIa of Clavien-Dindo classification, including 2 with esophagojejunal anastomosis leakage, 1 with duodenal stump leakage, and 1 with abdominal infection, and all these patients were recovered after conservative treatment. All the 67 patients were followed up. The mean nutrition index 12 months after surgery was 53.4±4.2, diameter of esophagojejunal anastomosis was (3.9±0.6) cm, the incidence of Roux-en-Y stasis syndrome was 3.0% (2/67), and the incidence of reflux esophagitis was 4.5% (3/67). No patient had recanalization of the closed input loop of esophagojejunal anastomosis, anastomotic stenosis, obstruction, or tumor recurrence at anastomosis. CONCLUSION: Intracavitary URY anastomosis following LTG for digestive tract reconstruction is safe and feasible, leading to fast postoperative recovery of digestive tract function and favorable short-term efficacy.

In vitro investigation of ultrasound-induced oxidative stress on human lens epithelial cells.

The effect of ultrasound exposure on human lens epithelial cells (HLE-B3) was investigated in vitro, specifically on the generation of oxidative stress upon ultrasound application using various clinically-relevant settings. In addition to ultrasound-induced heat effects, oxidative stress has been recently proposed as one of the main mechanisms for ultrasound-induced effects on human cells. In this work, the levels of biocompatibility and generation of oxidative stress by exposure of ultrasound to HLE-B3 were evaluated quantitatively and qualitatively by the MTT assay, Live/Dead assay, reactive oxygen species (ROS) and intracellular calcium level. Oxidative stress induction is traditionally achieved through administrations of H2O2 and thus the administration of H2O2 was used as the positive control group for comparison herein. Concerning the administrations of H2O2 are considered invasive and may potentially have side effects, ultrasound as physical stimulation could be a safer and non-invasive method to induce similar oxidative stress environments. The effect of ultrasound on cell viability and induction of oxidative stress increases with ultrasound intensity. The result reveals that the continuous ultrasound has a positive impact on the oxidative stress levels but does negatively on the cell viability, as compared to the pulsed ultrasound. Furthermore, our work demonstrates that the exposure of 58 kPa continuous ultrasound without microbubbles can maintain acceptable cell viability and produce oxidative stress effects similar to the traditional administrations of H2O2. In summary, exposure of ultrasound can generate oxidative stress comparable to traditional administrations of H2O2. The effect of generating oxidative stress is adjustable through ultrasound parameters, including the pulsed or continuous wave, the intensity of ultrasound and addition of microbubbles.

[Treatment of advanced metastatic breast cancer with exemestane, a multicenter randomized controlled study of 195 cases].

OBJECTIVE: To observe the efficacy of exemestane for postmenopausal advanced metastatic breast cancer, and to assess its side effects. METHODS: A randomized, double-blind, and parallel controlled study was conducted among 195 patients with postmenopausal advanced metastatic breast cancer from December 2001 to June 2002. Except for the 4 cases who were lost to follow-up, the remaining 191 patients were divided into two groups: study group (n = 96, treated with exemestane capsule 25 mg and one model tablet of letrozole orally q.d. for 8 weeks), and control group (n = 95, treated with letrozole 2.5 mg and one model capsule of exemestane orally q.d. for 8 weeks). Physical examination, roentgenography and CT were conducted to observe the outcome of the tumor and the level of estrogen was tested 2 weeks before and 4 and 8 weeks after the beginning of treatment. RESULTS: The effective rate was 44.8% in the study group and 45.3% in the control group (P = 0.971). The level of estradiol was 5.17 +/- 6.68 x 10(4) pg/L and 4.19 +/- 3.06 x 10(4) pg/L in the study group and control group respectively; and was 3.08 +/- 2.80 x 10(4) pg/L and 2.76 +/- 1.98 x 10(4) pg/L in the study group and control group respectively 8 weeks after the beginning of treatment, both decreased by 43.7% in comparison with those before treatment (both P < 0.001), however, there was no significant difference between the study group and control group (P = 0.141). The side effects of exemestane included thirst, giddiness, and nausea. CONCLUSION: An effective hormonal medicine, exemestane has good therapeutic efficacy in postmenopausal advanced metastatic breast cancer with only mild side effects.