Inflammatory cutaneous metastases originating from gastric cancer: A case report.

BACKGROUND: Cutaneous metastasis with gastric cancer (GC) origin is extremely rare and associated with poor prognosis. Nodular type is the most common type, while other forms are extremely rare. CASE SUMMARY: This study describes severe skin redness, swelling, pain, and fever in a 65-year-old man diagnosed with GC, whose left chest wall, left upper limb, and left back were mainly affected. Firstly, the patient was diagnosed with "lymphangitis" and treated to promote lymphatic return. However, the symptoms were constantly deteriorating, and skin thickening and scattered small nodules gradually appeared. Finally, the skin biopsy confirmed cutaneous metastases, and the patient died 7 d later. CONCLUSION: Our case highlights that cutaneous metastasis should be considered when skin lesions appear in patients with GC.

Combination therapy (toripalimab and lenvatinib)-associated toxic epidermal necrolysis in a patient with metastatic liver cancer: A case report.

BACKGROUND: Both programmed cell death-1 (PD-1) inhibitors and lenvatinib, which have a synergistic effect, are promising drugs for tumor treatment. It is generally believed that combination therapy with a PD-1 inhibitor and lenvatinib is safe and effective. However, we report a case of toxic epidermal necrolysis (TEN), a grade 4 toxicity, after this combination therapy. CASE SUMMARY: A 39-year-old male presented with erythema, blisters and erosions on the face, neck, trunk and limbs 1 wk after receiving combination therapy with lenvatinib and toripalimab, a PD-1 inhibitor. The skin injury covered more than 70% of the body surface area. He was previously diagnosed with liver cancer with cervical vertebra metastasis. Histologically, prominent necrotic keratinocytes, hyperkeratosis, liquefaction of basal cells and acantholytic bullae were observed in the epidermis. Blood vessels in the dermis were infiltrated by lymphocytes and eosinophils. Direct immunofluorescence staining was negative. Thus, the diagnosis was confirmed to be TEN (associated with combination therapy with toripalimab and lenvatinib). Full-dose and long-term corticosteroids, high-dose intravenous immunoglobulin and targeted antibiotic drugs were administered. The rashes gradually faded; however, as expected, the tumor progressed. Therefore, sorafenib and regorafenib were given in succession, and the patient was still alive at the 10-mo follow-up. CONCLUSION: Cautious attention should be given to rashes that develop after combination therapy with PD-1 inhibitors and lenvatinib. Large-dose and long-course glucocorticoids may be crucial for the treatment of TEN associated with this combination treatment.

Design, Synthesis, and Biological Activity of Chalcone Analogs Containing 4-Phenylquinolin and Benzohydrazide.

A series of chalcone derivatives (3a-3m) containing 4-phenylquinoline and benzohydrazide were designed and synthesized, and their anti-inflammatory, analgesic, and antidepressant activities were evaluated. Using the classic antidepressant model, except for compounds 3a and 3d, 11 compounds all showed certain antidepressant activity at a dose of 100 mg/kg, among which compounds 3f, 3h, and 3m showed good antidepressant activity (inhibition rate, respectively 63.0 %, 73.2 %, and 76.4 %), which was equivalent to the positive control fluoxetine (inhibition rate of 70.0 %). Secondly, the inhibitory activity of these compounds on mouse MAOA was evaluated. At 10 mM, compounds 3f and 3j showed a certain selective inhibitory effect on mouse MAOA , while compounds 3b, 3d, 3g, 3i, and 3m had a good inhibitory effect on mouse MAOA (inhibition rate is 42.3-71.4 %). The mouse ear edema model was used to evaluate the anti-inflammatory activity of compounds 3a-3m. At 30 mg/kg, compounds 3b, 3c, 3e, 3f, 3g, and 3m showed certain anti-inflammatory effects (inhibition rate of 51.5-99.9 %), which was equivalent to the positive control indomethacin (inhibition rate of 69.7 %). Results of the acetic acid-induced abdominal writhing test showed that, at 30 mg/kg, excepted for compounds 3a, 3b and 3d, all the other 10 compounds can show certain analgesic activity (inhibition rate 67-99.9 %). The use of Auto dock Vina (simina) to simulate molecular target docking shows that the development of quinoline and benzohydrazide groups is of great significance to MAOA inhibitors.

Nedaplatin-induced syndrome of inappropriate secretion of antidiuretic hormone: A case report and review of the literature.

BACKGROUND: Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is relatively common in several cancers, such as small cell lung cancer. However, nedaplatin-induced SIADH is rare. We describe a case of SIADH mediated by nedaplatin. CASE SUMMARY: A 54-year-old female with nasopharyngeal carcinoma was treated with nedaplatin and developed severe hyponatremia due to SIADH. The side effects were successfully treated by fluid restriction and sodium supplementation. CONCLUSION: This case report highlights the importance of cautiously treating life-threatening hyponatremia in patients treated with nedaplatin.

Synthesis and evaluations of selective COX-2 inhibitory effects: Benzo[d]thiazol analogs.

A series of benzo[d]thiazole analogs were synthesized and evaluated for their anti-inflammatory and analgesic effects. Using an ear edema model, except for compounds 2k, 2m-2q and 3a, other compounds showed the anti-inflammatory effects. Among them, compounds 2c, 2d, and 2g showed the best anti-inflammatory activity (inhibition rate: 86.8%, 90.7% and 82.9%, respectively). By the acetic acid-induced abdominal writhing test, except for compounds 2e, 2l, 2m, 2o, 2p and 3a, other compounds showed the analgesic effects with inhibition rate values of 51.9-100% (2a-2r) and 68.6-100% (3a-3g). Next, compounds 2c, 2d, 2g, 3d, 3f, 3g that displayed the excellent anti-inflammatory and analgesic activities were evaluated for their inhibitory effect against ovine COX-1 and COX-2. Compounds 2c, 2d, 2g, 3d, 3f, 3g were weak inhibitors of the COX-1 isozyme but exhibited the moderate COX-2 isozyme inhibitory effects IC50 from 0.28 to 0.77 µM and COX-2 selectivity indexes (SI: 18.6 to 7.2). This benzo[d]thiazole moiety will be proved to be of great significance for developing more potent COX-2 inhibitors.

[Research Progress on Genetic Factors and Hemophilia A Clotting Factor Inhibitor-Review].

Hemophilia A (Hemophilia A, HA) is an X-linked recessive hereditary coagulation function disorder, the deficiency and dysfunction of blood coagulation were caused by the mutations of gene encoding clotting factor VIII. The treatment of hemophilia A still depends on the replacement therapy with blood coagulation factor. However, the repeated infusion of clotting factor will produce the neutralizing antibody against FVIII, then resulting in one of the serious complications. The reports on the incidence of inhibitor are different at home and abroad. Due to diverse factors, the inhibitors of hemophilia A clotting factor mainly can be divided into genetic and environmental factors, In this review, the inhibitors of hemophilia A clotting factor and their risk factors are briefly summarized.

Inhibitory effects of Dioscin on atherosclerosis and foam cell formation in hyperlipidemia rats.

Macrophage-derived foam cells are well known for their key role in development of atherosclerosis (AS). The present study aimed to examine whether dioscin exerts anti-atherosclerotic activity and inhibits foam cell formation. A high-fat induced AS model and ox-LDL treated macrophages were established and received treatment of dioscin. Anti-atherosclerotic activity in vivo was assessed by atherosclerotic lesions size and aortic lipid contents. Macrophage formed foam cells were positively identified by oil red o staining. Moreover, the expression of LOX-1 and NF-κB in aorta tissue and macrophages was examined by western blotting assay. Our results showed that dioscin not only reduced the levels of plasma lipid, TNF-a, IL-1ß and IL-6, but also inhibited atherosclerotic development in AS rats, as evidenced by decreased atherosclerotic lesions size and aortic lipid level. In vitro study revealed dioscin directly reduced foam cell formation, decreased intracellular cholesterol accumulation and lowered TNF-a, IL-1ß and IL-6 secretion in ox-LDL treated macrophages. Interestingly, further work found dioscin significantly reduced expression of LOX-1 and NF-κB in the aortic tissue and ox-LDL treated macrophages. In summary, our study was the first to confirm anti-atherosclerotic activity of dioscin in vivo and vitro. Moreover, the other important finding is dioscin mediated ox-LDL/LOX-1/NF-κB regulated contributions to the attenuate macrophage ox-LDL uptake and AS.

Glucocorticoids Prevent Enterovirus 71 Capsid Protein VP1 Induced Calreticulin Surface Exposure by Alleviating Neuronal ER Stress.

Severe hand-foot-and-mouth disease (HFMD) caused by Enterovirus 71 (EV71) always accompanies with inflammation and neuronal damage in the central nervous system (CNS). During neuronal injuries, cell surface-exposed calreticulin (Ecto-CRT) is an important mediator for primary phagocytosis of viable neurons by microglia. Our data confirmed that brainstem neurons underwent neuronophagia by glia in EV71-induced death cases of HFMD. EV71 capsid proteins VP1, VP2, VP3, or VP4 did not induce apoptosis of brainstem neurons. Interestingly, we found VP1-activated endoplasmic reticulum (ER) stress and autophagy could promote Ecto-CRT upregulation, but ER stress or autophagy alone was not sufficient to induce CRT exposure. Furthermore, we demonstrated that VP1-induced autophagy activation was mediated by ER stress. Meaningfully, we found dexamethasone treatment could attenuate Ecto-CRT upregulation by alleviating VP1-induced ER stress. Altogether, these findings identify VP1-promoted Ecto-CRT upregulation as a novel mechanism of EV71-induced neuronal cell damage and highlight the potential of the use of glucocorticoids to treat severe HFMD patients with CNS complications.

Effects of CIK on hypoxia inducible factor-1α and T-cell subsets on colon 26 cancer xenograft mice.

Colorectal cancer is a common malignancy of the digestive tract with a high mortality rate. However, current treatment approaches such as radiotherapy and chemotherapy are ineffective. Thus, it is imperative to identify ways to treat recurrence and metastasis. The aim of the present study was to investigate the effects of cytokine-induced killer (CIK) cells on the hypoxia microenvironment and immune function in colon 26 cancer xenograft mice. A murine model of colon 26 carcinoma tumors were divided into CIK, normal saline (NS) and control groups. Hypoxia inducible factor-1α (HIF-1α) mRNA in tumor tissue and the small intestine of mice was detected by FQ-PCR. The percentage of the CD4+, CD8+ and CD4+/CD8+ ratio in the spleen of mice was detected by flow cytometry. The tumor volume in the CIK group was smaller than that in the NS group and the difference was not significant (P>0.05). HIF-1α gene expression was present in the tumor tissue and small intestine. HIF-1α gene expression in tumor tissue was significantly higher than that in the small intestine (P<0.05), and lower in tumor tissue of the CIK group compared to the NS group (P<0.05) of xenograft mice. However, no HIF-1α expression was observed in the small intestine of healthy control mice. CD4+ T-cell percentage and CD4+/CD8+ ratio in the spleen of xenograft mice was significantly lower than that of normal mice (P<0.05). Compared to the NS group, the CD4+ T-cell percentage was higher, whereas the CD8+ T-cell percentage was lower in the CIK group (P<0.05). In conclusion, HIF-1α gene expression was present in the tumor tissue and small intestine. The immune function of colon 26 transplanted in tumor mice was decreased. Additionally, CIK improved the microenvironment of tumor hypoxia and promoted immune reconstitution.

[Quercetin affects leptin and its receptor in human gastric cancer MGC-803 cells and JAK-STAT pathway].

AIM: Quercetin affects the expressions of leptin and its receptor in human gastric cancer MGC-803 cells and JAK-STAT pathway. METHODS: The cultured MGC-803 cells were divided into three groups: CONTROL GROUP: the cultured cells without quercetin, and Quercetin group: the cultured cells with quercetin(40 µmol/L), and AG490group: the cultured cells with AG490(40 µmol/L)The expressions of Leptin, Leptin receptor and P-STAT3 were detected in protein level by immunocytochemical and Western bloting method respectively. The expressions of Leptin, Leptin receptor were detected in mRNA level by RT-PCR method. MGC-803 cell cycle was arrest by flow cytometry (FCM); MGC-803 cell apoptosis ratio by apoptotic marker An-necxinV. RESULTS: The protein expression of Leptin, Leptin receptor, P-STAT3 and the the mRNA expression of Leptin and Leptin receptor were significantly increased (P<0.05), compared with the control group.There was the rectilinear correlation relationship not only between Leptin and P-STAT3 protein(r=0.741, P<0.05) but also between Leptin receptor and P-STAT3 protein(r=0.693, P<0.05). FCM analysis showed that quercetin arrested MGC-803 cells at the G2/M phase, The ratio of apoptotic and necrosic cells increased with added quercetin concentration. CONCLUSION: Quercetin could inhibit the Proliferation of MGC-803 cells. It is probably relevant to the down-regulation the expressions of Leptin and Leptin receptor protein, Leptin mRNA and Leptin receptor mRNA by JAK-STAT pathway.

[Effects of quercetin on the expression of VEGF-C and VEGFR-3 in human cancer MGC-803 cells].

AIM: To investigate the mechanism of quercetin on the inhibition of the lymphatic metastasis in human gastric cancer cells MGC-803. METHODS: Cells were divided into the control group and the quercetin (Que)-treated group. Immunohistochemistry and RT-PCR were used to detect the expression of vascular endothelial growth factor C (VEGF-C) and VEGFR-3 of human gastric cancer cells MGC-803 in response to Que. RESULTS: Que significantly decreased the expression of VEGF-C and VEGFR-3 at 40 mumol/L compared with the control group after 48 h (P<0.01). CONCLUSION: Que can down-regulate the expression of VEGF-C and VEGFR-3 in human gastric cancer cells MGC-803.

[Relationship between polymorphisms of FCGR2B and susceptibility of children idiopathic thrombocytopenic purpura].

The aim of study was to investigate the relationship between polymorphisms of FCGR2B232 1/T oligonucleotide and the susceptibility of children with idiopathic thrombocytopenic purpura (ITP). DNA from 76 patients with ITP and 37 controls was extracted. The SNPs of FCGR2B-232 was detected by polymerase chain reaction (PCR) combined with direct sequencing. The genotype distribution and allele frequency among different groups were compared. The results showed that the genotype (I/I, I/T, T/T) of FCGR2B-232 were 55.3%, 42.1%, and 2.6% in 76 patients with ITP, while 81.1%, 18.9%, 0% in 37 controls. The allele frequencies of FCGR2B-232 in patients with ITP were 76.3% (I232) and 23.7% (T232), but 90.5% and 9.5% in controls. There were significant differences in genotype distributions between the ITP patients and controls (chi(2) = 7.45, = 0.024). The enrichment in Thr232 allele carrier was also significant among the ITP patients as compared with the controls (chi(2) = 7.18, p = 0.007, odds ratio 3.47). There were also significant differences in allele frequencies between the ITP patients and controls [chi(2) = 6.54, p = 0.011, odds ratio 2.97, 95% CI (1.25 - 7.05)]. It is concluded that the polymorphisms of FCGR2B-232 significantly correlates with the susceptibility of children suffering from ITP. The minor Thr232 allele may be a risk genetic factor to ITP children.

[Quercetin inhibits growth and induces apoptosis of human gastric carcinoma cells].

AIM: To study the effect of quercetin on the growth and apoptosis of human gastric carcinoma cell line MGC-803. METHODS: The measurement of inhibitory rate and apoptotic index(AI) of quercetin were done by MTT assay and TUNEL assay. The positive expression rate of P53, C-myc and P16 were detected by immunocytochemical staining. RESULTS: Quercetin at concentrations ranging from 40 mumol/L to 100 mumol/L significantly inhibited the proliferation of MGC-803 cells in a dose- and time-dependent manner (P<0.01). TUNEL assay indicated that the number of apoptotic cells in quercetin-treated group was greater than that in the control group (P<0.01). Expression of P53 and C-myc protein decreased following quercetin induction in a dose-dependent manner, whereas P16 expression increased significantly compared with that of the control group (P<0.01). CONCLUSION: Quercetin can inhibit the growth and induce apoptosis of MGC-803 cells in a dose- and time-dependent manner. Its mechanisms may be relevant to the down-regulation of P53 and C-myc protein expression as well as up-regulation of P16 expression.