Gastric cancer is highly prevalent in China, yet early diagnosis and overall survival rates are low. The primary treatment strategy is comprehensive therapy centered on surgery. Studies indicate that ...neoadjuvant chemotherapy can enhance radical resection rates and extend survival in locally advanced gastric cancer. Combining VEGFR inhibitors with chemotherapy improves efficacy in digestive system tumors, while PD-1/PD-L1 inhibitors combined with anti-angiogenesis agents or chemotherapy show synergistic effects. This report presents a case of gastric adenocarcinoma (cT3N1M0) treated with SOX, apatinib mesylate, and camrelizumab as neoadjuvant therapy, followed by D2 distal gastrectomy and postoperative adjuvant therapy with the same regimen. The patient completed all treatment cycles successfully. Post-neoadjuvant therapy, only focal residual cancer cells were found in the lamina propria (pT1a). During postoperative adjuvant therapy follow-up, gastroscopic biopsy indicated a pathological complete response with no recurrence or metastasis. The patient primarily experienced dyspepsia, oropharyngeal pain, capillary proliferation, mild bone marrow suppression, nausea, and vomiting as side effects. Therefore, SOX combined with apatinib mesylate and camrelizumab shows promise for treating resectable locally advanced gastric cancer.
Helicobacter pylori (H. pylori) is a gram-negative pathogen that colonizes gastric epithelial cells. The drug resistance rates of H. pylori have dramatically increased, causing persistent infections. ...Chronic infection by H. pylori is a critical cause of gastritis, peptic ulcers and even gastric cancer. In host cells, autophagy is stimulated to maintain cellular homeostasis following intracellular pathogen recognition by the innate immune defense system. However, H. pylori-induced autophagy is not consistent during acute and chronic infection. Therefore, a deeper understanding of the association between H. pylori infection and autophagy in gastric epithelial cells could aid the understanding of the mechanisms of persistent infection and the identification of autophagy-associated therapeutic targets for H. pylori infection. The present review describes the role of H. pylori and associated virulence factors in the induction of autophagy by different signaling pathways during acute infection. Additionally, the inhibition of autophagy in gastric epithelial cells during chronic infection was discussed. The present review summarized H. pylori-mediated autophagy and provided insights into its mechanism of action, suggesting the induction of autophagy as a novel therapeutic target for persistent H. pylori infection.
One of the most important and striking characteristics of hepatocellular carcinoma (HCC) with intrahepatic metastasis, is that it results in extremely poor prognosis. Animal models have become a ...fundamental and very useful in research for disease study. However, some limitation has arisen from these model systems. We have therefore established a model of HCC with intrahepatic metastasis and noticed some differential appearances in different HCC cell lines. Luciferase-transfected HCC cell lines MHCC97-H and PLC/PRF/5 were inoculated into SCID mice via spleen. Observation the intrahepatic metastasis by bioluminescence imaging in vivo and comparing of the differential formation of metastatic lesions between different HCC cell lines by incorporating physical anatomy was done. Animal models for HCC intrahepatic metastasis were well established. However, there were some clearly noticed differences between MHCC97-H and PLC/PRF/5 cell lines. The group of MHCC97-H cell line readily metastasis in the liver, whereas group PLC/PRF/5 cell line developed extensive intrahepatic metastasis and formed large tumor in situ in the spleen. MHCC97-H and PLC/PRF/5 cell lines can be used to successfully establish a model of HCC intrahepatic metastasis with distinctive characteristics, which provides an important direction for the study of the mechanism of HCC intrahepatic metastasis, and may hopefully provide a basis for clinical treatment.
Metastatic colon cancer remains an incurable disease, and it is difficult for existing treatments to achieve the desired clinical outcome, especially for colon cancer patients who have received ...first-line treatment. Although immune checkpoint inhibitors (ICIs) have demonstrated durable clinical efficacy in a variety of solid tumors, their response requires an inflammatory tumor microenvironment. However, microsatellite-stable (
) colon cancer, which accounts for the majority of colorectal cancers, is a cold tumor that does not respond well to ICIs. Combination regimens open the door to the utility of ICIs in cold tumors. Although combination therapies have shown their advantage even for
colon cancer, it remains unclear whether combination therapies show their advantage in patients with pretreated metastatic colon cancer. We report a patient who has achieved complete remission and good tolerance with sintilimab plus bevacizumab and platinum-based chemotherapy after postoperative recurrence. The patient had
mutation and
-type colon cancer, and his PD-1
CD8
and CD3
CD19
CD14
CD16
HLA-DR were both positive. He has achieved a progression-free survival of 43 months and is still being followed up at our center. The above results suggest that this therapeutic regimen is a promising treatment modality for the management of pretreated,
-type and
-mutated metastatic colorectal cancer although its application to the general public still needs to be validated in clinical trials.
BackgroundThe high metastasis rate is one of the main reasons for the poor prognosis of patients with hepatocellular carcinoma (HCC). Coagulation factor Xa (FXa) and its receptor proteinase-activated ...receptor-2 (PAR-2) proven to promote tumor metastasis in other forms of cancer. Here, we explore the role and mechanism of FXa in the regulation of resistance of anoikis and immune escape of HCC.MethodsIn vitro and in vivo experiments were conducted to explore the role of FXa in HCC metastasis and its potential mechanism. The effects of FXa inhibitor rivaroxaban on HCC immunotherapy were evaluated using intrahepatic metastasis animal models and clinical trial (No. ChiCTR20000040540). We investigated the potential of FXa inhibition as a treatment for HCC.ResultsFXa was highly expressed in HCC and promoted metastasis by activating PAR-2. Mechanistically, FXa-activated PAR-2 endows HCC cells with the ability of anoikis resistance to survive in the circulating blood by inhibiting the extrinsic apoptosis pathway. Furthermore, suspension stimulation-induced phosphorylation of STAT2, which promotes programmed death-ligand 1 (PD-L1) transcription and inhibits the antitumor effects of immune cells by inhibiting the infiltration of CD8+T cells in tumors and the levels of secreted cytokines. In vivo inhibition of FXa with rivaroxaban reduced HCC metastasis by decreasing PD-L1 expression and exhausting tumor-infiltrating lymphocytes. Notably, the combination of rivaroxaban and anti-programmed death-1 monoclonal antibody (anti-PD-1) programmed Death-1 monoclonal antibody (anti-PD-1) induced synergistic antitumor effects in animal models. Most importantly, rivaroxaban improved the objective response rate of patients with HCC to immune checkpoint inhibitors and prolonged overall survival time.ConclusionsFXa-activated PAR-2 promotes anoikis resistance and immune escape in HCC, suggesting the potential for combining coagulation inhibitors and PD-1/PD-L1 immune checkpoint blockade to enhance the therapeutic efficacy of HCC.
Acupuncture is used to treat subjects with occipital neuralgia, which is 1 of the main causes of occipital pain; however, its effect is conflicting. Hence, the current study aims to evaluate the ...effects of acupuncture in the treatment of occipital neuralgia.
In a systematic search of PubMed, Embase, OVID, China National Knowledge Infrastructure, Cochrane Library, Chinese Biomedical Literature Database, Wanfang databases, and Google Scholar until July 2021, 15 studies aimed to evaluate the effects of acupuncture in the treatment of occipital neuralgia were included. Human-related trials were considered in different languages. The size of the study was not considered a limit for its inclusion and the study intervention should focus on comparing the impact of acupuncture in the intervention group compared with the control group.The odds ratio (OR) and the mean difference (MD) with 95% confidence intervals (CIs) were calculated with a random or fixed-effect model for different subgroup analyses. Publication bias was assessed using the Egger test, while the risk of bias was assessed using the Review manager software.
Acupuncture had a significantly higher effective rate of treatment (OR, 5.40; 95% CI, 2.48 to 11.77, P < .001) compared to control in the treatment of occipital neuralgia and lower visual analogue scale (MD, -2.45; 95% CI, -2.69 to -2.21, P < .001). Acupuncture plus medication had a significantly higher effective rate of treatment (OR, 3.96; 95% CI, 2.10 to 7.47, P < .001) compared to medication in the treatment of occipital neuralgia. Acupuncture analysis for safety issues showed a significant reduction of adverse events compared with the medication group.
Acupuncture alone or acupuncture plus medication had a significantly beneficial effect on the effective rate of treatment, safety and visual analog scale compared to medication in the treatment of occipital neuralgia. Further studies are required to validate these findings.
Cholestasis is an important cause of liver fibrosis and cirrhosis. Yinchenhao decoction has been used as a well‐known traditional Chinese medicine used in the treatment of cholestasis for over 2,000 ...years. The purpose of this systematic review is to evaluate the preclinical evidence of Yinchenhao decoction on cholestasis models. The following databases were searched from inception to February 2020. Chinese National Knowledge Infrastructure, VIP medicine information system, Wanfang Database, PubMed, Web of Science, Embase and the Cochrane Library were searched. The content concerned Yinchenhao decoction on different animal model experiments for the treatment of cholestasis. The methodological quality of the included studies was assessed based on the SYstematic Review Center for Laboratory animal Experimentation Animal Experiment Bias Risk Assessment Tool. A meta‐analysis was conducted with RevMan 5.3 software according to the Cochrane tool. Nineteen studies on a total of 404 animals were included with five kinds of experimental animal models. The results showed that serum total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin and total bile acid in the group treated with Yinchenhao decoction were significantly lower than those in the model group (P < 0.00001). The alanine aminotransferase (ALT), aspartate aminotransferase and alkaline phosphatase levels in the Yinchenhao decoction group were also significantly reduced (P < 0.00001). The subgroup analysis of the different models showed that Yinchenhao decoction had a significant effect on the bile duct ligation model, and there was a significant reduction in TBIL, DBIL and ALT levels (P < 0.00001) in ANIT‐induced cholestasis. After 24 hours of Yinchenhao decoction treatment, there was no significant difference in TBIL levels (P = 0.34), but after 48 and 72 hours of treatment, the TBIL levels were significantly reduced compared with the model group (P < 0.00001). There was no significant difference in DBIL after 48 hours of administration (P = 0.26), but compared with the model group, Yinchenhao decoction could significantly reduce the DBIL levels after 48 hours of treatment (P < 0.0003). Yinchenhao decoction could significantly reduce the ALT levels after 24, 48 and 72 hours (P < 0.006). Yinchenhao decoction was able to significantly reduce the levels of TBIL, DBIL and ALT on different rat species: Wistar and Sprague Dawley (P = 0.0001; P = 0.0002). The preclinical evidence indicated that Yinchenhao decoction might be a potent and promising agent for cholestasis. Moreover, this conclusion should be further confirmed with more well‐designed researches.
Workflow of present study.
The cover image is based on the Review
Preclinical evidence of Yinchenhao decoction on cholestasis: A systematic review and meta‐analysis of animal studies
by Kaiyun Shi et al.,
...https://doi.org/10.1002/ptr.6806
.
image
Cholestasis is an important cause of liver fibrosis and cirrhosis. Yinchenhao decoction has been used as a well‐known traditional Chinese medicine used in the treatment of cholestasis for over 2,000 ...years. The purpose of this systematic review is to evaluate the preclinical evidence of Yinchenhao decoction on cholestasis models. The following databases were searched from inception to February 2020. Chinese National Knowledge Infrastructure, VIP medicine information system, Wanfang Database, PubMed, Web of Science, Embase and the Cochrane Library were searched. The content concerned Yinchenhao decoction on different animal model experiments for the treatment of cholestasis. The methodological quality of the included studies was assessed based on the SYstematic Review Center for Laboratory animal Experimentation Animal Experiment Bias Risk Assessment Tool. A meta‐analysis was conducted with RevMan 5.3 software according to the Cochrane tool. Nineteen studies on a total of 404 animals were included with five kinds of experimental animal models. The results showed that serum total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin and total bile acid in the group treated with Yinchenhao decoction were significantly lower than those in the model group (
P
< 0.00001). The alanine aminotransferase (ALT), aspartate aminotransferase and alkaline phosphatase levels in the Yinchenhao decoction group were also significantly reduced (
P
< 0.00001). The subgroup analysis of the different models showed that Yinchenhao decoction had a significant effect on the bile duct ligation model, and there was a significant reduction in TBIL, DBIL and ALT levels (
P
< 0.00001) in ANIT‐induced cholestasis. After 24 hours of Yinchenhao decoction treatment, there was no significant difference in TBIL levels (
P
= 0.34), but after 48 and 72 hours of treatment, the TBIL levels were significantly reduced compared with the model group (
P
< 0.00001). There was no significant difference in DBIL after 48 hours of administration (
P
= 0.26), but compared with the model group, Yinchenhao decoction could significantly reduce the DBIL levels after 48 hours of treatment (
P
< 0.0003). Yinchenhao decoction could significantly reduce the ALT levels after 24, 48 and 72 hours (
P <
0.006). Yinchenhao decoction was able to significantly reduce the levels of TBIL, DBIL and ALT on different rat species: Wistar and Sprague Dawley (
P
= 0.0001;
P
= 0.0002). The preclinical evidence indicated that Yinchenhao decoction might be a potent and promising agent for cholestasis. Moreover, this conclusion should be further confirmed with more well‐designed researches.
Background and Aim
It has been well documented that Helicobacter pylori (H. pylori) infection is a risk factor for aggravating gastric mucosal atrophy. However, the exact molecular mechanism ...mediating this process is not fully elucidated. The purpose of this study was to identify biomarkers, which may predict the risk for progression of chronic atrophic gastritis (CAG) with H. pylori.
Methods
GSE27411 was downloaded from the Gene Expression Omnibus. The differentially expressed genes (DEGs) between H. pylori‐infected samples without CAG and H. pylori‐infected CAG samples were analyzed. Gene Ontology and pathway enrichment analyses were performed, followed by protein–protein interaction network construction. We used immunohistochemistry analysis to identify DEGs in 20 chronic gastritis, 20 CAG, and 22 gastric cancer (GC) specimens.
Results
A total of 303 upregulated and 26 downregulated DEGs were identified. The pathways enriched by upregulated DEGs were mainly related to fat digestion and absorption, peroxisome proliferator‐activated receptor signaling pathway, and chemical carcinogenesis. Cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) had the highest degrees in protein–protein interaction network. Moreover, the positive rates of CYP3A4 protein expression in chronic gastritis, CAG, and GC were 10% (2/20), 55% (11/20), and 77.3% (17/22), respectively (P < 0.001). The Kaplan–Meier analysis revealed that elevated expression of CYP3A4 was significantly associated with worse overall survival and first progression, respectively (P < 0.0001).
Conclusion
According to the findings of this study, the expression of CYP3A4 might be related to the potential carcinogenic transformation of CAG to GC. Therefore, CYP3A4 may be biomarkers to predict progression of CAG and poor prognosis of gastric cancer.
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