OBJECTIVE: To explore the efficacy and safety of human epidermal growth factor gel in the treatment of pin tract infections after surgery in patients with severe spinal deformity. METHODS: A retrospective case-control study was conducted to analyze the clinical data of 26 patients with pin tract infections after skull-pelvic ring traction for severe spinal deformity admitted from February 2019 to May 2022. Among them, 11 were male and 15 were female;the age ranged from 18 to 31 years, with an average of (24.1±4.3) years;the Cobb angle ranged 80.3° to 120.7°, with an average of (88.6±10.2)°;there were 52 iliac traction pins, 104 pin tract openings, and 38 pin tract infections. According to the Checketts-Otterbum classification, there were 11 infections of gradeⅠ, 13 infections of gradeⅡ, 10 infections of grade Ⅲ, and 4 infections of grade Ⅳ. The patients were divided into the conventional dressing change group (13 cases) and the growth factor group (13 cases) by coin flipping. Clinical efficacy was evaluated by recording the visual analogue scale(VAS) score during dressing change, duration of dressing change, cost of dressing change, positive rate of bacterial culture, wound improvement rate, and wound improvement time. RESULTS: There were no statistically significant differences in VAS or duration of dressing change between the two groups (P>0.05). The cost of dressing change was (800.0±59.5) yuan in the conventional dressing change group and (1 179.5±80.9) yuan in the growth factor group, with a statistically significant difference (P<0.05). There was no statistically significant difference in the positive rate of bacterial culture between the two groups (P>0.05). In the conventional dressing change group, within 20 pin tract infections, 2 infections achieved wound healing, 7 infections showed improvement, and 11 infections were ineffective;in the growth factor group, within 18 pin tract infections 5 infections achieved wound healing, 8 infections showed improvement, and 5 infections were ineffective, with a statistically significant difference between the two groups (P<0.05). The wound healing time was (22.8±4.9) days in the conventional dressing change group and (14.2±2.5) days in the growth factor group, with a statistically significant difference (P<0.05). No complications occurred in either group. CONCLUSION The application of human epidermal growth factor gel in the treatment of pin tract infections after skull-pelvic ring surgery in patients with severe spinal deformity is easy to operate, does not increase patient pain, and has significant efficacy. It shortens wound healing time, effectively promotes wound healing, and has good safety and high cost-effectiveness.
Humans ; Male ; Female ; Adult ; Adolescent ; Retrospective Studies ; Case-Control Studies ; Young Adult ; Epidermal Growth Factor/therapeutic use* ; Traction/adverse effects* ; Gels ; Bone Nails/adverse effects* ; Surgical Wound Infection/drug therapy*

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) can effectively inhibit the growth of EGFR-dependent mutant non-small cell lung cancer (NSCLC). Unfortunately, NSCLC patients often develop severe drug resistance after long-term EGFR-TKI treatment. Studies have shown that the disorder of energy metabolism in tumor cells can induce EGFR-TKI resistance. Due to the drug action, gene mutation and other factors, tumor cells undergo metabolic reprogramming, which increases the metabolic rate and intensity of tumor cells, promotes the intake and synthesis of nutrients (such as sugar, fat and glutamine), forms a microenvironment conducive to tumor growth, enhances the bypass activation, phenotype transformation and abnormal proliferation of tumor cells, and inhibits the activity of immune cells and apoptosis of tumor cells, ultimately leading to drug resistance of tumor cells to EGFR-TKI. Therefore, targeting energy metabolism of NSCLC may be a potential way to alleviate TKI resistance.
Carcinoma, Non-Small-Cell Lung/genetics* ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; Epidermal Growth Factor ; ErbB Receptors/genetics* ; Humans ; Lung Neoplasms/genetics* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Tumor Microenvironment

PURPOSE: Molecular testing in non-small cell lung cancer (NSCLC) aids in identifying oncogenic alterations. The aim of this study was to compare the rates of detection of oncogenic alterations and responsiveness to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) according to EGFR mutation status as determined by peptide nucleic acid (PNA) clamping or direct sequencing (DS). MATERIALS AND METHODS: We performed a systematic literature search using MEDLINE, EMBASE, and the Cochrane Central Register. Data from included studies were pooled to yield summary sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and receiver operating characteristic curves. A meta-regression analysis was conducted to identify potential sources of heterogeneity between selected studies. RESULTS: We identified 10 studies comprising 924 patients. Oncogenic alterations were detected in 340 of 924 cases (36.8%) with PNA clamping and in 250 of 924 (27.1%) with DS. The pooled sensitivities of PNA clamping and DS were 0.93 [95% confidence interval (CI): 0.90−0.95] and 0.69 (95% CI: 0.64−0.73), respectively. According to meta-regression analysis, none of the covariates were found to be significant sources of heterogeneity. With respect to treatment responses to EGFR-TKIs, there was no significant difference therein between EGFR mutations detected by PNA clamping and DS (53.4% vs. 50.8%; risk ratio, 0.99; 95% CI 0.83−1.19; p=0.874). CONCLUSION: We demonstrated that PNA clamping has a higher sensitivity than DS for detecting oncogenic alterations in NSCLC. Our findings suggest that PNA clamping is a more useful method for clinical practice.
Antineoplastic Agents/therapeutic use ; Carcinoma, Non-Small-Cell Lung/drug therapy/*genetics ; Constriction ; Humans ; Lung Neoplasms/*genetics ; Molecular Diagnostic Techniques ; Mutation ; Peptide Nucleic Acids/*genetics ; Protein Kinase Inhibitors/*therapeutic use ; Receptor Protein-Tyrosine Kinases/*genetics ; Receptor, Epidermal Growth Factor/*genetics ; Sensitivity and Specificity ; Sequence Analysis ; Sequence Analysis, DNA ; Translocation, Genetic

PURPOSE: Rearrangement of the proto-oncogene rearranged during transfection (RET) has been newly identified potential driver mutation in lung adenocarcinoma. Clinically available tyrosine kinase inhibitors (TKIs) target RET kinase activity, which suggests that patients with RET fusion genes may be treatable with a kinase inhibitor. Nevertheless, the mechanisms of resistance to these agents remain largely unknown. Thus, the present study aimed to determine whether epidermal growth factor (EGF) and hepatocyte growth factor (HGF) trigger RET inhibitor resistance in LC-2/ad cells with CCDC6-RET fusion genes. MATERIALS AND METHODS: The effects of EGF and HGF on the susceptibility of a CCDC6-RET lung cancer cell line to RET inhibitors (sunitinib, E7080, vandetanib, and sorafenib) were examined. RESULTS: CCDC6-RET lung cancer cells were highly sensitive to RET inhibitors. EGF activated epidermal growth factor receptor (EGFR) and triggered resistance to sunitinib, E7080, vandetanib, and sorafenib by transducing bypass survival signaling through ERK and AKT. Reversible EGFR-TKI (gefitinib) resensitized cancer cells to RET inhibitors, even in the presence of EGF. Endothelial cells, which are known to produce EGF, decreased the sensitivity of CCDC6-RET lung cancer cells to RET inhibitors, an effect that was inhibited by EGFR small interfering RNA (siRNA), anti-EGFR antibody (cetuximab), and EGFR-TKI (Iressa). HGF had relatively little effect on the sensitivity to RET inhibitors. CONCLUSION: EGF could trigger resistance to RET inhibition in CCDC6-RET lung cancer cells, and endothelial cells may confer resistance to RET inhibitors by EGF. E7080 and other RET inhibitors may provide therapeutic benefits in the treatment of RET-positive lung cancer patients.
Adenocarcinoma/drug therapy/*genetics ; Cell Line, Tumor ; Cetuximab/pharmacology ; Drug Resistance, Neoplasm/drug effects/*genetics ; Epidermal Growth Factor/metabolism/*pharmacology ; *Gene Rearrangement ; Hepatocyte Growth Factor/*pharmacology ; Humans ; Indoles/pharmacology ; Lung Neoplasms/drug therapy/*genetics ; MAP Kinase Signaling System ; *Mutation ; Niacinamide/analogs & derivatives/pharmacology ; Phenylurea Compounds/pharmacology ; Piperidines/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Proto-Oncogene Proteins c-ret/*antagonists & inhibitors/genetics ; Pyrroles/pharmacology ; Quinazolines/pharmacology ; RNA, Small Interfering/pharmacology ; Receptor, Epidermal Growth Factor/genetics/metabolism ; Signal Transduction/drug effects ; fms-Like Tyrosine Kinase 3/metabolism

PURPOSE: Traditional chemotherapy is the main adjuvant therapy for the treatment of non-small cell lung cancer (NSCLC). However, the emergence of multi-drug resistance (MDR) has greatly restricted the curative effect of chemotherapy. Therefore, it is necessary to find a method to treat MDR NSCLC clinically. It is worth investigating whether NSCLCs that are resistant to traditional chemotherapy can be effectively treated with tyrosine kinase inhibitors targeting epidermal growth factor receptor (EGFR). MATERIALS AND METHODS: The expression of P-glycoprotein (P-gp) and lung resistance-related protein (LRP) was detected by immunohistochemistry, and mutations in EGFR (exons 19 and 21) and Kirsten rat sarcoma viral oncogene homolog (KRAS) (exon 2) were detected by high-resolution melting analysis (HRMA) of surgical NSCLC specimens from 127 patients who did not undergo traditional chemotherapy or radiotherapy. A Pearson chi-square test was performed to analyze the correlations between the expression of P-gp and LRP and mutations in EGFR and KRAS. RESULTS: The expression frequencies of P-gp and LRP were significantly higher in adenocarcinomas from non-smoking patients; the expression frequency of LRP was significantly higher in cancer tissue from female patients. The frequency of EGFR mutations was significantly higher in well to moderately differentiated adenocarcinomas from non-smoking female patients. The frequency of EGFR mutations in the cancers that expressed P-gp, LRP, or both P-gp and LRP was significantly higher than that in cancers that did not express P-gp or LRP. CONCLUSION: NSCLCs expressing P-gp/LRP bear the EGFR mutation in exon 19 or 21 easily.
Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung/*genetics/surgery ; Exons/*genetics ; Female ; Humans ; Lung Neoplasms/*genetics/pathology/surgery ; Middle Aged ; Mutation ; P-Glycoprotein/*genetics ; Protein Kinase Inhibitors/therapeutic use ; Proto-Oncogene Proteins/*genetics ; Proto-Oncogene Proteins p21(ras) ; Receptor, Epidermal Growth Factor/*genetics ; Treatment Outcome ; Vault Ribonucleoprotein Particles/*genetics ; ras Proteins/*genetics

OBJECTIVETo study the curative effect of Zhiyang Pingfu Liquid (ZPL) in treating epidermal growth factor receptor inhibitors (EGFRIs) associated adverse reactions of the skin.

METHODSAll 54 patients with pathologically confirmed malignant tumor had EGFRIs induced adverse reactions of the skin to various degrees. ZPL was externally applied for them all, once or twice per day, 14 days consisting of one therapeutic course. Changes of adverse skin reactions, time for symptoms relief, adverse skin reaction types suitable for ZPL were observed before and after treatment.

RESULTSEGFRIs associated skin adverse reactions were improved to various degrees after they used ZPL. The shortest symptoms relief time was 1 day while the longest was 12 days, with an average of 6.93 days and the median time 7 days. Compared with before treatment, itching, rash/scaling, acne/acneform eruptions were obviously improved (P < 0.05).

CONCLUSIONZPL could alleviate EGFRls associated adverse skin reactions, especially showed better effect on itching, rash/scaling, acne/acneform eruptions.

Antineoplastic Agents ; adverse effects ; Biomedical Research ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Exanthema ; chemically induced ; Humans ; Neoplasms ; drug therapy ; Pruritus ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; Skin ; drug effects ; Skin Diseases ; drug therapy

BACKGROUND: Anti-Gal is a major antibody induced in non-human primates (NHPs) after xenotransplantation. To understand the mechanism of graft rejection, we investigated the association between anti-Gal responses and graft failure in NHP recipients of porcine islet transplantation (PITx). METHODS: Intraportal PITx was performed in 35 diabetic NHPs, and graft function was monitored. Early graft failure (EGF) was defined as loss of graft function within a month after PITx. Seven, 19, nine NHPs received immunosuppression (IS) without CD40 pathway blockade (Group I), with anti-CD154 (Group II), and with anti-CD40 (Group III), respectively. The anti-Gal levels on day 0 and day 7 of PITx were measured by ELISA. RESULTS: The frequency of EGF was significantly lower in Group II (26.3%) than in Group I (100%, P=0.0012) and Group III (77.8%, P=0.0166). While levels of anti-Gal IgG in Group I and anti-Gal IgM in Group III increased on day 7 compared with day 0 (P=0.0156 and 0.0273), there was no increase in either on day 7 in Group II. The ratio of anti-Gal IgM or IgG level on day 7 to that on day 0 (Ratio7/0) was significantly higher in recipients with EGF than without EGF (P=0.0009 and 0.0027). ROC curve analysis of anti-Gal IgM Ratio7/0 revealed an area under the curve of 0.789 (P=0.0003). CONCLUSIONS: IS with anti-CD154 suppressed anti-Gal responses and prevented EGF in PITx. Anti-Gal IgM Ratio7/0, being associated with EGF, is a predictive marker for EGF.
Animals ; Antibodies/blood/immunology ; Antigens, CD40/immunology ; Area Under Curve ; CD40 Ligand/immunology ; Disaccharides/*immunology ; Epidermal Growth Factor/blood ; Graft Rejection/*immunology ; Immunoglobulin G/blood ; Immunoglobulin M/*blood ; Immunosuppressive Agents/therapeutic use ; *Islets of Langerhans Transplantation ; Macaca mulatta ; ROC Curve ; Swine ; Transplantation, Heterologous

BACKGROUND/AIMS: The purpose of this study was to identify predictive factors for erlotinib treatment in non-small cell lung cancer (NSCLC) patients following gefitinib failure. METHODS: Forty-five patients with NSCLC who were treated with erlotinib following gefitinib failure at Seoul National University Hospital between August 2005 and November 2011 were enrolled. Epidermal growth factor receptor (EGFR) mutation status, pathologic findings and other clinical factors, including response to tyrosine kinase inhibitors (TKIs) and progression-free survival (PFS), were evaluated. RESULTS: Of the 45 patients, 40 patients (88.8%) had adenocarcinoma. The following EGFR mutations were observed: five patients with a deletion of exon 19, six patients with an L858R mutation, three patients with wild-type EGFR, and 31 patients with unknown mutations. The response rate of erlotinib was 4.4%, and stable disease was 42.2%. The median PFS for erlotinib was 2.6 months (95% confidence interval, 1.4 to 3.7). Patients with a PFS > or = 4 months during previous gefitinib treatment had a significantly longer PFS with erlotinib (3.3 months vs. 1.6 months, respectively; p < 0.01) than patients with PFS < 4 months with gefitinib. According to multivariate analyses, PFS > or = 4 months for previous gefitinib treatment was significantly associated with prolonged PFS with erlotinib (p = 0.04). However, the response rate of gefitinib and treatment sequence were not associated with prolonged PFS with erlotinib (p = 0.28 and p = 0.67, respectively). CONCLUSIONS: Following rechallenge with the EGFR TKI erlotinib following gefitinib failure, patients who showed prolonged PFS with gefitinib benefit from erlotinib. However, further prospective studies are needed to confirm these findings.
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents/*therapeutic use ; Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/pathology ; Chi-Square Distribution ; Disease-Free Survival ; Erlotinib Hydrochloride/*therapeutic use ; Female ; Hospitals, University ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/*drug therapy/genetics/pathology ; Male ; Middle Aged ; Multivariate Analysis ; Mutation ; Proportional Hazards Models ; Protein Kinase Inhibitors/*therapeutic use ; Quinazolines/*therapeutic use ; Receptor, Epidermal Growth Factor/antagonists & inhibitors/genetics ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Salvage Therapy ; Time Factors ; Treatment Failure

OBJECTIVETo compare the efficacy of the erlotinib versus gefitinib in the first-line treatment of patients with advanced EGFR mutation-positive NSCLC.

METHODSFifty patients with untreated advanced EGFR mutation- positive NSCLC were randomly divided into gefitinib group (n=27) and erlotinib group (n=23). The progression-free survival, objective response rate and disease control rate were evaluated to compare the efficacy of gefitinib and erlotinib.

RESULTSThere were no significant differences in the objective response rate (P=0.711) and disease control rate (P=0.861) between the two groups. The progression-free survival of gefitinib group and erlotinib group was 8.0 months and 10.0 months, respectively. The efficacy of the two drugs was similar (P=0.293).

CONCLUSIONThere is no significant differences between gefitinib and erlotinib in the first-line treatment of patients with advanced EGFR mutation-positive NSCLC.

Carcinoma, Non-Small-Cell Lung ; drug therapy ; Disease-Free Survival ; Erlotinib Hydrochloride ; Humans ; Lung Neoplasms ; drug therapy ; Mutation ; Quinazolines ; therapeutic use ; Receptor, Epidermal Growth Factor ; metabolism

Small molecule covalent inhibitors, or called as irreversible inhibitors, are a type of inhibitors that exert their biological functions by irreversibly binding to target through covalent bonds. Compared with non-covalent inhibitors, covalent inhibitors have obvious advantages in bioactivity. Nevertheless, these agents may also exhibit larger toxicity once off-target effects arise. This "double-edged swords" property often leads drug researchers to avoid attaching them. In recent years, some problems such as drug resistance are difficult to be solved with reversible inhibitors leading researchers to pay more attention on the covalent inhibitors. In this review, we shall make a short summary to the recent research progress of covalent inhibitors and the interaction modes between covalent inhibitors and their target protein residues.
Amino Acids ; chemistry ; Antineoplastic Agents ; chemical synthesis ; chemistry ; therapeutic use ; Antiviral Agents ; chemical synthesis ; chemistry ; therapeutic use ; Drug Discovery ; Drug Resistance ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; therapeutic use ; Hepatitis C ; drug therapy ; Humans ; Molecular Structure ; Neoplasms ; drug therapy ; Protein Binding ; Protein Kinase Inhibitors ; chemical synthesis ; chemistry ; therapeutic use ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; Serine Proteinase Inhibitors ; chemical synthesis ; chemistry ; therapeutic use