Epidermal growth factor (EGF) promotes chemomigration of a human prostate tumor cell line,and EGF immunoreactive proteins are present at sites of metastasis in the stroma of lymph nodes and medullary bone

Prostate tumor cells preferentially metastasize to bony sites and lymph nodes at a frequency in excess of that which would be predicted by random tumor cell dissemination. In order to determine whether chemoattractants in these organs promote organ-specific metastasis, we utilized human cell lines derived from and/or related to these organs as sources of potential chemoattractants. Secretory proteins derived from the cell lines MG-63 (osteosarcoma), SK-ES-1 (Ewing's sarcoma), and KG-1 (leukemia) stimulated chemomigration of the TSU-pr1 prostate tumor cells in a dose-dependent manner in Boyden chambers. In addition, secretory proteins from a human prostatic stromal cell line (hPS) and from the TSU-Pr1 prostate tumor cell line were also able to stimulate chemomigration of the TSU-pr1 cells through Boyden chambers. Since lymph nodes and bony sites represent organs of hematopoietic/lymphoid proliferation and activation, we undertook identification of specific cytokines present at these sites which may promote the chemomigration of prostate tumor cells. In this context, the cytokines interleukin-1α, interleukin-2, interleukin-6, tumor necrosis factor-β, transforming growth factor-β, interferon α2-a, and granulocyte-macrophage colony-stimulating factor did not stimulate chemomigration of the TSU-pr1 prostate tumor cell line. In contrast, the cytokine epidermal growth factor (EGF) stimulated chemomigration of the TSU-pr1 prostate tumor cells through the Boyden chambers in a dose-dependent manner. Western blot analysis of secretory proteins from the cell lines KG-1, SK-ES-1, MG-63, hPS, and TSU-pr1 identified EGF-immunoreactive proteins in all cases. In addition, EGF immunoreactivity was localized to the stroma of the human prostate, the osteogenic stroma of pelvic medullary bone, and the stroma within the capsule and trabeculae of pelvic lymph nodes. Hence, these results demonstrate that the cytokine EGF promotes the chemomigration of the TSU-pr1 prostate tumor cell line, and that EGF within the stroma of pelvic lymph nodes and medullary bone may act as a chemoattractant for prostate tumor cells, thereby facilitating the preferential formation of metastatic foci within these organs. © 1996 Wiley-Liss, Inc.     

Evaluation of epidermal growth factor receptor, transforming growth factor alpha, epidermal growth factor and c-erbB2 in the progression of invasive bladder cancer

Introduction: Determination of the risk of invasive bladder tumors progressing is still imprecise due to the heterogeneous biological behavior of this neoplasm. The goals of this study were to evaluate the patterns of expression of the epidermal growth factor (EGF) system in invasive bladder cancer and to assess its prognostic value. Methods: This immunohistochemical study was performed using fresh frozen tumor samples and a panel of monoclonal antibodies on a series of 43 invasive bladder cancers treated by cystectomy. Results: EGF was detected in 45% of the tumors and did not correlate with survival from bladder cancer. Transforming growth factor alpha (TGF) was expressed by 60% of the tumors and correlated strongly with death from bladder cancer. Epidermal growth factor receptor (EGF-R) expression was seen in 86% of cases and had no prognostic significance. cerbB2 was expressed in 50% of cases and was inversely related to a poor prognosis. When EGF and TGF were both expressed, there was little or no expression of c-erbB2. Conclusion: The accumulation of several growth factors and the relevant receptor are necessary for the progression of invasive bladder cancers. They could be used as indicators of tumor aggressiveness.     

Epidermal growth factor stimulates lactate production and inhibits aromatization in cultured Sertoli cells from immature rats

The addition of epidermal growth factor (EGF) at nanomolar concentrations to cultures of Sertoli cells from 16-day-old rats induced more than a 2-fold stimulation of lactate production after 12 h of incubation. The effects of EGF, insulin and FSH on lactate production were very similar and the concentrations that produced half maximal stimulation were 11, 22 and 25 ng/ml or, in molar terms, 1.8, 3.5 and 0.6 nM for EGF, insulin and FSH, respectively. No synergistic or additive effects of these hormones on lactate production could be demonstrated. In contrast, EGF inhibited FSH-stimulated oestradiol synthesis by more than 50%. Insulin had no effect on FSH-stimulated aromatization.     

Etomidate – a review of robust evidence for its use in various clinical scenarios

Etomidate is an intravenous hypnotic with a favourable clinical profile in haemodynamic high‐risk scenarios. Currently, there is an active debate about the clinical significance of the drug's side effects and its overall risk–benefit ratio. Etomidate‐induced transient adrenocortical suppression is well documented and has been associated with increased mortality in sepsis. In surgical patients at risk of hypotensive complications, however, a review of current literature provides no robust evidence to contraindicate a single‐bolus etomidate induction. Large randomised controlled trials as well as additional observational data are required to compare safety of etomidate and its alternatives.     

Epidermal growth factor receptor gene expression and binding capacity in renal cell carcinoma,in relation to tumor stage,grade and DNA ploidy

Epidermal growth factor receptor (EGFr) was studied in 19 renal cell carcinomas using competitive binding analysis and solution hybridization sssay. EGFr binding capacity and EGFr mRNA expression were significantly higher in tumors in comparison with kidney cortex tissues. The EGFr binding capacity was higher in diploid than in aneuploid tumors. No differences in binding capacities or mRNA expression between different tumor grades or stages were demonstrated. It was concluded that EGFr is overexpressed in renal cell carcinoma, although with no relationship to tumor characteristics.     

Peripherally inserted central catheters in infants and children – indications,techniques, complications and clinical recommendations

Venous access required both for blood sampling and for the delivery of medicines and nutrition is an integral element in the care of sick infants and children. Peripherally inserted central catheters (PICCs) have been shown to be a valuable alternative to traditional central venous devices in adults and neonates. However, the evidence may not extrapolate directly to older paediatric patients. In this study, we therefore review the indications, methods of insertion and complications of PICC lines for children beyond the neonatal age to provide clinical recommendations based on a search of the current literature. Although the literature is heterogeneous with few randomised studies, PICCs emerge as a safe and valuable option for intermediate‐ to long‐term central venous access in children both in and out of hospital. Insertion can often be performed in light or no sedation, with little risk of perioperative complications. Assisted visualisation, preferably with ultrasound, yields high rates of insertion success. With good catheter care, rates of mechanical, infectious and thrombotic complications are low and compare favourably with those of traditional central venous catheters. Even in the case of occlusion or infection, fibrinolytics and antibiotic locks often allow the catheter to be retained.     

肝细胞生长因子在胃癌病人血清中的表达及意义

目的:肝细胞生长因子(hepatocyte growth factor,HGF)是一种多肽生长因子,其促进细胞增殖,诱导细胞迁移、侵袭及参与血管生成,在肿瘤发生发展过程中具有重要作用。本研究通过检测胃癌病人血清HGF水平,分析其与胃癌临床病理特征的关系,并与常用肿瘤标志物CA19-9、CEA进行比较,探讨胃癌病人血清中HGF的表达及其临床意义。方法:用酶联免疫吸附夹心法检测80例胃癌病人术前血清HGF、CA19-9、CEA水平,并观察60例病人根治术后血清HGF变化。结果:胃癌病人血清HGF水平(2.94±2.67)μg/L明显高于正常对照组(1.02±0.31)μg/L(P=0.002);分层分析发现,随着疾病的进展,血清HGF水平逐渐升高[Ⅰ期(2.19±2.12)μg/L,Ⅱ期(2.53±2.38)μg/L,Ⅲ期(3.92±3.45)μg/L,Ⅳ期(4.13±3.71)μg/L];Ⅲ期和Ⅳ期分别与Ⅰ期进行比较,均有显著差异(P<0.05)。另外,80例病人血清HGF、CA19-9和CEA的阳性率分别为80%、16.2%和5.0%,HGF阳性率明显较高(P<0.01)。结论:胃癌病人血清HGF水平明显高于正常对照组,且血清HGF的表达水平与胃癌淋巴结及肝脏转移呈正相关.血清HGF表达水平可作为反映胃癌生物学行为和判断预后的参考指标。     

Transactivation of epidermal growth factor receptor after heparin-binding epidermal growth factor-like growth factor shedding in the migration of prostate cancer cells promoted by bombesin

BACKGROUND: A pathway consisting of bombesin, G-protein coupling receptors (GPCRs), metalloproteases, pro-heparin-binding epidermal growth factor (proHB-EGF), and epidermal growth factor receptor (EGFR) has been reported in prostate cancer cells. The occurrence of HB-EGF shedding from proHB-EGF in this pathway, however, has not been proven directly. In addition, it is still unclear how much this pathway contributes to the migration of prostate cancer cells. In this study, we tried to directly elucidate HB-EGF shedding in this pathway and to determine its contribution to the migration of prostate cancer cells. METHODS: RT-PCR and indirect immunofluorescence staining for HB-EGF and its receptors, such as EGFR and HER4/erbB4, were performed on PC-3 cells. The influences of bombesin, anti-EGFR neutralizing monoclonal antibody, HB-EGF, and HB-EGF shedding inhibitor on the migration of PC-3 cells were studied by means of in vitro wound assays. The amount of HB-EGF shed from PC-3 cells with alkaline phosphatase-tagged HB-EGF in the presence of bombesin was determined by measuring AP activity. Immunoprecipitations and phosphotyrosine Western blotting were performed to detect EGFR transactivated by bombesin. RESULTS: PC-3 expressed HB-EGF and EGFR, but not HER4/erbB4. PC-3 migrated in the presence of bombesin, but its migration was partly inhibited by the neutralizing antibody against EGFR. PC-3 also migrated in the presence of HB-EGF, but HB-EGF shedding inhibitor partly inhibited this phenomenon. HB-EGF was shed from PC-3 cells in the presence of bombesin, and this shedding was inhibited by HB-EGF shedding inhibitor. In addition, the EGFR on PC-3 was activated in the presence of bombesin and inactivated in the presence of HB-EGF shedding inhibitor. CONCLUSIONS: These results indicated that HB-EGF shedding and the following transactivation of EGFR occurs in this pathway and that this pathway partly contributes to the migration of prostate cancer cells.     

Quantitative evaluation of the bacteriostatic efficacy of amniotic membrane applied as a biological dressing over large contaminated wounds encountered in clinical practice

Summary Control of wound infection constitutes the most important aspect of wound management. A successful wound closure either by delayed primary/secondary suturing or by skin grafting cannot be performed unless the bacterial count in the tissues is well below the critical number of 10⁵ organisms per gram of tissue. In this study, the efficacy of the amniotic membrane in reducing bacterial infection when applied as a biological dressing over granulating wounds was compared with that of standard saline dressings. Bacteriological monitoring of wound flora was achieved by a three dimensional biopsy from an active portion of the infected wound. Such biopsies were taken from both test and control areas before membrane application and 72 h after application. The results of this study demonstrate that amnion dressings have a definite and significant antibacterial effect as seen by the marked decrease in bacterial colony counts after the dressing is applied to contaminated wounds. This effect of the amnion can be attributed to the intimate biological closure due to its excellent adherence on to the wound bed, facilitation of phagocytosis of the micro-organisms in the underlying healthier granulations and to certain antibacterial substances elaborated by the living amniotic cells.Presented at the Peet Prize Scientific Session of the 24th National Conference of the Association of Plastic Surgeons of India at Baroda, September 2, 1989     

Epidermal growth factor receptor (EGFR)—tyrosine kinase inhibitors as a first-line treatment for postoperative recurrent and EGFR-mutated non-small-cell lung cancer

 Open in a separate windowOBJECTIVESTo clarify survival outcomes and prognostic factors of patients receiving epidermal growth factor receptor (EGFR) - tyrosine kinase inhibitors (TKIs) as first-line treatment for postoperative recurrence.METHODSA retrospective chart review was performed to identify consecutive patients who received EGFR-TKIs as first-line treatment for postoperative recurrence of non-small-cell lung cancer (NSCLC) harbouring EGFR gene mutations at our institution between August 2002 and October 2020. Therapeutic response, adverse events, progression-free survival (PFS) and overall survival (OS) were investigated. Survival outcomes were assessed using the Kaplan–Meier analysis. The Cox proportional hazards model was used for univariable and multivariable analyses.RESULTSSixty-four patients were included in the study. The objective response and disease control rates were 53% and 92%, respectively. Grade 3 or greater adverse events were noted in 4 (6.3%) patients, including 1 patient (1.6%) of interstitial pneumonia. The median follow-up period was 28.5 months (range 3–202 months). The total number of events was 43 for PFS and 23 for OS, respectively. The median PFS was 18 months, and the median OS was 61 months after EGFR-TKI treatment. In multivariable analysis, osimertinib showed a tendency to prolong PFS [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.12–1.1; P = 0.071], whereas the micropapillary component was significantly associated with shorter OS (HR 2.1, 95% CI 1.02–6.9; P = 0.045).CONCLUSIONSEGFR-TKIs as first-line treatment appeared to be a reasonable treatment option in selected patients with postoperative recurrent EGFR-mutated NSCLC. Osimertinib and the micropapillary component may be prognostic factors.     

Pressure ulcers in cardiac surgery: Few clinical studies,difficult risk assessment,and profound clinical implications

Pressure ulcers (PUs) are a common complication after cardiac surgery, with almost one third of patients suffering from PUs during hospitalisation. Because of the burden that PUs exert on both the patients and the health care system, prevention is of utmost importance. The first step in successful prevention, however, includes the identification of the main features that render patients prone to PU development. Cardiac surgery population is not adequately addressed in current clinical trials and studies. Few studies focused specifically on cardiac surgery patients, but the majority included cardiac surgery patients within a heterogeneous population of acute or critical care patients. Therefore, additional research is warranted to understand the unique risk profile of patients undergoing cardiac surgery. Intraoperative risk factors that affect tissue tolerance have not been thoroughly investigated but are likely to play an important role, which might explain the epidemiology of a PU. Further research is also needed to better comprehend the risk of PUs among cardiac surgery patients and to design effective and tailored preventative measures with the help of newer tools for risk assessment.     

Exemestane: a review of its clinical efficacy and safety

Aromatase inhibitors and inactivators are playing an increasing greater role in breast cancer treatment. Exemestane, a highly specific, steroidal aromatase inactivator, is the newest agent in this class. The drug is highly specific, and inhibits the in vivo conversion of androstenedione to oestrone (aromatization) by a mean of 97.9%. Exemestane has shown good efficacy and tolerability in multiple clinical trials among patients with metastatic breast cancer who have failed one or more previous hormonal therapies. Exemestane 25 mg/day slows disease progression and reduces tumour-related signs and symptoms and the drug exhibits a partial lack of cross-resistance with the non-steroidal aromatase inhibitors. Response rates to exemestane of 14% to 29% were observed including patients with visceral metastases, who have historically proven difficult to treat. In a large phase III trial, exemestane was found to be superior to megestrol acetate with respect to time to progression and overall survival. In addition, exemestane is currently under investigation as first-line therapy in metastatic disease and in sequence with tamoxifen in the adjuvant setting. Adverse events include low-grade hot flashes, nausea, and fatigue--mostly of mild to moderate intensity--and treatment-related discontinuations are rare. In conclusion, exemestane represents a novel and interesting drug for the treatment of advanced breast cancer, with exciting prospects for use in adjuvant therapy and, potentially, breast cancer prevention.     

Use of negative pressure wound therapy on malignant wounds – a case report and review of literature

The presence of malignancy is considered a contraindication to the use of negative pressure wound therapy (NPWT) because of concerns that it may promote tumourigenesis and expedite metastasis. This notion is extrapolated from studies evaluating NPWT in normal tissues. Despite the absence of direct evidence, the use of this technology in malignant wounds is widely considered a contraindication. We present the case of a patient with treatment‐resistant metastatic colon cancer, who developed a chronic abdominal wound with positive margins. A staged reconstruction using NPWT was performed and wound closure allowed the patient to meet eligibility criteria and enrol in a clinical trial for treatment of his oncological disease. Skin closure remained intact until the patient expired 6 months after the wound closure. This case, as well as others in the literature, demonstrated that the use of NPWT should not be considered an absolute contraindication in malignancy. Individualised approaches taking into account the patient's clinical scenario, the available evidence, as well as the risks and benefits of this technology are recommended.     

Growth fractions of breast cancer in relation to epidermal growth factor receptor and estrogen receptor

Growth fractions detected by a monoclonal antibody, Ki-67, were examined in 40 human breast cancer tissues and the results compared with the immunocytochemical reactivities of epidermal growth factor receptor (EGFR) and estrogen receptor (ER). The proportion of proliferating cells displaying Ki-67 positive staining was significantly higher in the EGFR positive tumors than in the EGFR negative tumors (p<0.01). The average percentage of Ki-67 positive cells in the EGFR positive tumors was 19.9 per cent, whereas that in the EGFR negative tumors was 8.0 per cent. By contrast, an inverse relationship between the proportion of proliferating cells and ER positive cells detected by anti-ER monoclonal antibody was observed. This data indicated the difference in growth fractions with relation to the EGFR and ER status of breast cancer.     

The efficacy and safety of epidermal growth factor in treatment of diabetic foot ulcers: the preliminary results

Objective: To evaluate the efficacy and safety of recombinant human epidermal growth factor (rh‐EGF) in healing foot ulcers in diabetic patients. Methods: A total of 28 subjects with foot ulcers were recruited into the pilot study. Patients who had obvious peripheral arterial disease, trans‐tibial amputation, plastic surgery or skin flap, and skin graft were excluded. The properly debrided wounds and the non closure wounds after toe amputation were included. When the wounds became clean or uninfected, they received twice‐a‐day treatment with 0·005% Easyef and hydrocolloid dressing. The size and severity of the wounds were evaluated. Others such as blood sugar, renal and hepatic function, serum albumin, vascular condition, foot infection or osteomyelitis were assessed. Results: All of 28 patients had positive response of granulation (100%). Complete healing was noted in 13 out of 23 subjects and finished 8‐week follow‐up (56·5%). The rates of wound closure were 43·3%, 59·9%, 68·7%, and 84·8% in week 2, 4, 6 and 8, respectively, regardless of the severity. Being dropped out, three patients needed further interventions. No skin allergic reaction. Over‐granulation was observed in one female patient (3·7%), but as minor. Conclusions: Easyef has positive effects on healing of moderate‐to‐severe foot ulcers and demonstrated being safe to diabetic patients. The drug had high tolerability and compliance.