Research progress in targeted therapies for gastric cancer.

Patients with advanced gastric cancer experience rapid disease progression with limited survival, high mortality, and a lack of surgical options. Thus, radiochemotherapy or a combination of chemotherapeutics with targeted therapy is the mainstay of treatment. In comparison to the treatment of other malignant tumors, in gastric cancer, the development of molecularly targeted drugs has been relatively slow. Currently, there are two major classes of molecularly targeted drug regimens that have achieved a certain efficacy in clinical practice: anti-vascular endothelial growth factor (anti-VEGF) therapy and anti-epidermal growth factor receptor (anti-EGFR) therapy. Trastuzumab has been approved as the standard of care for first-line treatment in advanced human epidermal growth factor receptor 2 (HER2)-positive gastric cancer. Ramucirumab in combination with paclitaxel is the recommended regimen for second-line treatment, and apatinib is recommended as third-line treatment. This review summarizes the current status of targeted therapies in the treatment of gastric cancer and gives a perspective on the future.

Virtual Reality in Treatment for Psychological Problems in First-Line Health Care Professionals Fighting COVID-19 Pandemic: A Case Series.

ABSTRACT: Virtual reality therapy (VRT) is a new psychotherapeutic approach integrating virtual reality technology and psychotherapy. This case series aimed to study effectiveness of VRT in treating psychological problems. We described four cases of first-line health care professionals with emerging clinically significant early psychological problems during the COVID-19 outbreak, and specifically received the VRT treatment. We compared the Patient Health Questionnaire 9 items (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), PHQ-15, and Athens Insomnia Scale to evaluate psychological symptoms and sleep quality before and after sessions. All four cases showed a reduction in scale comparison. General scores of the PHQ-9 reduced 65%, GAD-7 reduced 52.17%, PHQ-15 decreased 38.17%, and scores of the Athens Insomnia Scale reduced 67.44%. Meanwhile, a reduction in depression, anxiety, psychosomatic, and sleeping symptoms was also found, which decreased 76.92% in general. These results are highly significant statistically. This case series demonstrated the effectiveness of VRT on psychological problems as a promising approach to apply on various psychological distress and disorders.

Concurrent Comparison of the Prognostic Values of Tumor Budding, Tumor Stroma Ratio, Tumor Infiltrating Pattern and Lymphocyte-to-Monocyte Ratio in Colorectal Cancer Patients.

Objectives: Tumor budding (TB), tumor stroma ratio (TSR), tumor infiltrating pattern (TIP), and preoperative lymphocyte-to-monocyte ratio (LMR) were previously reported to be useful prognostic factors in colorectal cancer (CRC); however, the correlation among these markers and their individual prognostic potency have not been extensively studied. Methods: A cohort of 147 stage I-IV CRC patients was obtained retrospectively, and the patients were divided into subgroups based on low or high TB/TSR/LMR, TIPa (expansile + intermediate) and TIPb (infiltrative) values. The differences in relapse-free survival (RFS) and overall survival (OS) intervals among these subgroups were determined by Kaplan-Meier analysis followed by log-rank tests. The Cox proportional hazard model was applied for the univariate and multivariate analysis of RFS and OS rates. Results:TB, TIP, and LMR, but not TSR, are useful markers for predicting patient survival. Patients with a poor histological grade and large tumor diameter were more likely to present with high TB, TIPb, and low LMR values; in addition, those with advanced T, N, and TNM stages and elevated preoperative CA199 levels had high TB and TIPb levels. TB, TIP, and LMR were significant prognostic factors for the RFS (TB: HR [hazard ratio] = 2.28, 95% CI = 1.30-4.00, P < .01; TIP: HR = 2.60, 95% CI = 1.46-4.60, P < .01; LMR: HR = 0.79, 95% CI = 0.65-0.96, P = .02) and OS (TB: HR = 2.43, 95% CI = 1.32-4.48, P < .01; TIP: HR = 2.49, 95% CI = 1.34-4.63, P < .01; LMR: HR = 0.79, 95% CI = 0.64-0.98, P = .03) intervals. In addition, TB and LMR were independent prognostic factors for the RFS interval (TB: HR = 1.80, 95% CI = 1.01-3.19, P = .05; LMR: HR = 0.80, 95% CI = 0.67-0.96, P = .01), but only LMR was an independent factor for OS rates (HR = 0.80, 95% CI = 0.65-0.98, P = .03). Conclusion: Although TB, TIP, and LMR are useful prognostic markers for CRC, the LMR is likely to be the only independent prognostic factor for both RFS and OS outcomes in practice.

Emotional disorder syndrome after cosmetic facial injection.

There are a number of patients who develop severe anxiety or depression after receiving facial cosmetic injections. We presented a 32-year-old woman who developed frequent panic, tension headache, tachycardia, shortness of breath, and sleep disorder for a year after the injection of hyaluronic acid on her forehead and glabella. Brain magnetic resonance imaging (MRI) showed multiple flaky and slightly longer T1, slightly longer T2 signals on the anterior frontal white matter. However, the patient's brain MRI scan 5 months before the injection showed no such performance. The patient was asked to consult the psychiatrist and was diagnosed with anxiety disorder. We name such phenomenon by Emotional disorder syndrome after cosmetic facial injection and assume that there are three major reasons for the emergence of this syndrome. One reason may be that emotional disorder is caused by the mental state of the patient. The second reason to explain the emotional disorder might be the frontal lobe syndrome caused by the frontal embolism during the filler injection. Another reason may be leukoaraiosis, a brain white matter change which may cause depression and anxiety.

Voluntary exercise increases adult hippocampal neurogenesis by increasing GSK-3ß activity in mice.

Exercise has been proven to promote learning and memory, and is closely related to increased adult neurogenesis in the hippocampus. In our study, the ß subunit of Glycogen synthase kinase-3 (GSK3ß) can be significantly regulated by exercise, and the modulation of GSK3ß activity can enhance adult neurogenesis and memory. To explore the mechanism by which exercise can improve cognitive function and adult neurogenesis, and the role GSK3ß plays in this process, we established a mouse model of voluntary exercise to examine the expression and activity of GSK3ß, and its associated signaling pathways, in the hippocampus dentate gyrus. The results showed an obvious increase in adult neurogenesis and cognitive functions, and the up-regulation of GSK3ß, after exercise. The activity of the insulin pathway, which negatively regulates GSK3ß, was also increased. Moreover, our results showed that the dopamine D1 receptor (DARP D1) pathway and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) were also activated, which indicates a relationship between GSK3ß and neurogenesis. Overall, our findings demonstrated that voluntary exercise promotes cognition and neurogenesis in the adult mouse dentate gyrus by the regulation of GSK3ß expression and activity, which may be implemented through the DARP D1 receptor-signaling pathway.

[Effect of Jinlongshe Granule Drug-containing Serum on Tube Formation, Migration and Apoptosis of Human Lymphatic Endothelial Cells in vitro].

Objective To observe the inhibitory effect of Jinlongshe Granule drug-containing serum (JG-DS) on tube formation, migration, and apoptosis of human lymphatic endothelial cells ( HLECs) in vitro. Methods JG-DS was prepared. The 3rd-passage HLECs were divided into the control group (cultured with normal saline containing serum) and the experimental group (cultured with JG-DS). After cultured for 12 h, the tube formation ability was detected by Matrigel assay, and the migration ability was determined by Transwell assay in the two groups. Cell apoptosis rate was detected by flow cytometry and Annexin-V-FITC/Pl staining method. Results The total length of tube was (3 084. 49 ?326. 27) p.m after acted by 10% JG-DS for 12 h, significantly shorter than that of the control group (7 058.93 ?4 567. 39) pm (P <0.01). The migration number of HLECs was (99 ?26), obviously lower than that of the control group (160 ?32; P <0.05). The apoptosis rate of the two groups was not statistically significant (P >0.05). Conclusion JG could inhibit the tube formation and migration of HLECs in vitro, which might be one of mechanisms for inhibiting tumor micro-lymphatics.

Secondary acute promyelocytic leukemia following chemotherapy for gastric cancer: a case report.

Therapy-related acute myeloid leukemia (t-AML) refers to a heterogeneous group of myeloid neoplasms that develop in patients following extensive exposure to either cytotoxic agents or radiation. The development of t-AML has been reported following treatment of cancers ranging from hematological malignancies to solid tumors; however, to our knowledge, t-AML has never been reported following treatment of gastric cancer. In this study, we report the development of t-acute promyelocytic leukemia in a cT4N1M0 gastric cancer patient after an approximate 44 mo latency period following treatment with 4 cycles of oxaliplatin (OXP) (85 mg/m(2) on day 1) plus capecitabine (1250 mg/m(2) orally twice daily on days 1-14) in combination with recombinant human granulocyte-colony stimulating factor treatment. Karyotype analysis of the patient revealed 46,XY,t(15;17)(q22;q21)[15]/46,idem,-9,+add(9)(p22)[2]/46,XY[3], which, according to previous studies, includes some "favorable" genetic abnormalities. The patient was then treated with all-trans retinoic acid (ATRA, 25 mg/m(2)/d) plus arsenic trioxide (ATO, 10 mg/d) and attained complete remission. Our case illuminated the role of certain cytotoxic agents in the induction of t-AML following gastric cancer treatment. We recommend instituting a mandatory additional evaluation for patients undergoing these therapies in the future.

ß -Elemene-Attenuated Tumor Angiogenesis by Targeting Notch-1 in Gastric Cancer Stem-Like Cells.

Emerging evidence suggests that cancer stem cells are involved in tumor angiogenesis. The Notch signaling pathway is one of the most important regulators of these processes. ß -Elemene, a naturally occurring compound extracted from Curcumae Radix, has been used as an antitumor drug for various cancers in China. However, its underlying mechanism in the treatment of gastric cancer remains largely unknown. Here, we report that CD44+ gastric cancer stem-like cells (GCSCs) showed enhanced proliferation capacity compared to their CD44- counterparts, and this proliferation was accompanied by the high expression of Notch-1 (in vitro). These cells were also more superior in spheroid colony formation (in vitro) and tumorigenicity (in vivo) and positively associated with microvessel density (in vivo). ß -Elemene was demonstrated to effectively inhibit the viability of GCSCs in a dose-dependent manner, most likely by suppressing Notch-1 (in vitro). ß -Elemene also contributed to growth suppression and attenuated the angiogenesis capacity of these cells (in vivo) most likely by interfering with the expression of Notch-1 but not with Dll4. Our findings indicated that GCSCs play an important role in tumor angiogenesis, and Notch-1 is one of the most likely mediators involved in these processes. ß -Elemene was effective at attenuating angiogenesis by targeting the GCSCs, which could be regarded as a potential mechanism for its efficacy in gastric cancer management in the future.