GRP78 Protein Expression in Ovarian Cancer Patients and Perspectives for a Drug-Targeting Approach

Glucose-regulated protein of 78 kD (GRP78) is a chaperone protein mainly located in the endoplasmic reticulum (ER). This protein is normally present at low levels in adult cells but its expression is triggered by ER stress including glucose deprivation and hypoxia. In tumor cells, it is overexpressed with fraction of protein found at the cell surface. This paper presents the physiology of GRP78 in the context of ovarian cancer and its potential use as drug delivery systems targeting ovarian cancer cell

Occult Nosocomial Infections

Even with a good surveillance program, nosocomial infections may be not recognized because of several reasons: absence of symptoms or prolonged incubation period (eg, viral bloodborne infections, tuberculosis); problems with the microbiological diagnosis, because adequate specimens may be difficult to obtain or special methods should be used (eg, fungal infections, virus, new agents); shorter hospital stays (eg, surgical-site infections); difficulty in distinguishing between nosocomial and community-acquired infections (eg, influenza); and failure to detect clinically relevant colonization (eg, multiresistant microorganisms). Because of the important potential consequences of occult nosocomial infections, specific surveillance programs should be designed to address these problem

GRP78-targeted nanotherapy against castrate-resistant prostate cancer cells expressing membrane GRP78

Glucose-regulated protein 78, GRP78, is a chaperone protein mainly located in the endoplasmic reticulum (ER) of normal cells. In stress conditions, GRP78 is overexpressed and in different cancer cell types, it is expressed at the cell surface, whereas it stays intracellular in non-cancerous cells. Therefore, it appears as a strategic target to recognize malignant cells. Prostate cancer is one of the most diagnosed cancers in men. The development of castrate resistant tumors and the resistance to chemotherapy frequently occur. The carboxy-terminal ER retention domain is defined by the KDEL amino acid sequence. We developed anti-KDEL functionalized polymeric nanoparticles (NPs) loaded with paclitaxel (Tx) to specifically target prostate cancer cells expressing GRP78. The sensitivity to Tx in different formulations was compared in three prostate cell lines: PNT1B, a normal cell line, PC3, a cancer cell line faintly expressing GRP78 at its surface, and DU145, a cancer cell line expressing GRP78 at its cell surface. Our results show that the targeted formulation significantly increases Tx sensitivity of cell line expressing GRP78 at its surface compared to other treatments suggesting the added value of GRP78 targeted therapy for castrate resistant tumor which expresses GRP78 at its cell surfac

Is genetic analysis useful in the routine management of hydatidiform mole?

Complete hydatidiform mole and partial hydatidiform mole are two abnormal conceptuses that may be identified by clinical, ultrasonographic, gross morphological, histological, and genetic characteristics. Among all these criteria, the specific diagnosis is generally confirmed only upon histological review. However, an accurate diagnosis based on morphological criteria is difficult and several studies have shown that misclassifications are frequent, even for experienced pathologists. An erroneous diagnosis may imply that women are either not enrolled in an adequate β‐hCG follow‐up with the risk that hydatidiform mole (HM) progresses to choriocarcinoma, or are enrolled in an unnecessary follow‐up. A reliable and complementary method to the pathologic interpretation is a genetic study of the conceptus to eliminate the diagnostic dilemma by distinguishing non‐molar spontaneous abortions from HM and to define the type of HM. The aim of our study was to review the genetic basis of HM and discuss its relevance in the routine management of the disorde

Quantitative Antibiogram as a Typing Method for the Prospective Epidemiological Surveillance and Control of MRSA Comparison with Molecular Typing

Abstract Objective: Evaluation of the quantitative antibiogram as an epidemiological tool for the prospective typing of methicillin-resistant Staphylococcus aureus (MRSA), and comparison with ribotyping. Methods: The method is based on the multivariate analysis of inhibition zone diameters of antibiotics in disk diffusion tests. Five antibiotics were used (erythromycin, clindamycin, cotrimoxazole, gentamicin, and ciprofloxacin). Ribotyping was performed using seven restriction enzymes (EcoRV, HindIII, KpnI, PstI, EcoRI, SfuI, and BamHI). Setting: 1,000-bed tertiary university medical center. Results: During a 1-year period, 31 patients were found to be infected or colonized with MRSA. Cluster analysis of antibiogram data showed nine distinct antibiotypes. Four antibiotypes were isolated from multiple patients (2, 4, 7, and 13, respectively). Five additional antibiotypes were isolated from the remaining five patients. When analyzed with respect to the epidemiological data, the method was found to be equivalent to ribotyping. Among 206 staff members who were screened, six were carriers of MRSA. Both typing methods identified concordant of MRSA types in staff members and in the patients under their care. Conclusions: The quantitative antibiogram was found to be equivalent to ribotyping as an epidemiological tool for typing of MRSA in our setting. Thus, this simple, rapid, and readily available method appears to be suitable for the prospective surveillance and control of MRSA for hospitals that do not have molecular typing facilities and in which MRSA isolates are not uniformly resistant or susceptible to the antibiotics teste

Importation of Acinetobacter baumannii Into a Burn Unit: A Recurrent Outbreak of Infection Associated With Widespread Environmental Contamination

A burn patient was infected with Acinetobacter baumannii on transfer to the hospital after a terrorist attack. Two patients experienced cross-infection. Environmental swab samples were negative for A. baumannii. Six months later, the bacteria reemerged in 6 Patients. Environmental swab samples obtained at this time were inoculated into a minimal mineral broth, and culture results showed widespread contamination. No case of infection occurred after closure of the unit for disinfectio

Comparison of Automated Strategies for Surveillance of Nosocomial Bacteremia

Objective. Surveillance of nosocomial bloodstream infection (BSI) is recommended, but time-consuming. We explored strategies for automated surveillance. Methods. Cohort study. We prospectively processed microbiological and administrative patient data with computerized algorithms to identify contaminated blood cultures, community-acquired BSI, and hospital-acquired BSI and used algorithms to classify the latter on the basis of whether it was a catheter-associated infection. We compared the automatic classification with an assessment (71% prospective) of clinical data. Setting. An 850-bed university hospital. Participants. All adult patients admitted to general surgery, internal medicine, a medical intensive care unit, or a surgical intensive care unit over 3 years. Results. The results of the automated surveillance were 95% concordant with those of classical surveillance based on the assessment of clinical data in distinguishing contamination, community-acquired BSI, and hospital-acquired BSI in a random sample of 100 cases of bacteremia. The two methods were 74% concordant in classifying 351 consecutive episodes of nosocomial BSI with respect to whether the BSI was catheter-associated. Prolonged episodes of BSI, mostly fungemia, that were counted multiple times and incorrect classification of BSI clinically imputable to catheter infection accounted for 81% of the misclassifications in automated surveillance. By counting episodes of fungemia only once per hospital stay and by considering all cases of coagulase-negative staphylococcal BSI to be catheter-related, we improved concordance with clinical assessment to 82%. With these adjustments, automated surveillance for detection of catheter-related BSI had a sensitivity of 78% and a specificity of 93%; for detection of other types of nosocomial BSI, the sensitivity was 98% and the specificity was 69%. Conclusion. Automated strategies are convenient alternatives to manual surveillance of nosocomial BS

Report of the 7th international workshop on colposcopy, screening and prevention of cervical cancer, Douala, Cameroon, March 30 - 31 and April 1st 2016

Background: Authors herein report the proceedings of the 7th international workshop on colposcopy, screening and prevention of cervical cancer held in Douala (Cameroon) on March 30 - 31 and April 1, 2016.Methods: As with previous conferences of this series, the 2016 edition provided an excellent forum for exchange of information and opinions between the researchers, clinicians, laboratory scientists and regulatory bodies. It also stood as an opportunity for further training of health staff on prevention and screening of cervical cancer.Results: The workshop covered both accepted and emerging methods of preventing and screening cervical cancer with emphasis on current clinical and public health practice in low and middle-income countries.  The topic was covered by complementary sessions: cervical principles, cervical cancer epidemiology and prevention strategy; cervical cancer management and treatment; cervical cancer screening programs in Cameroon; innovations in cervical cancer screening and perspectives in cervical cancer screening. This report also summarizes the presentations done during the workshop. This 7th edition set up the record of attendance with more than 150 participants of several backgrounds (specialist physicians and nurses, laboratory technicians, socio-anthropologists, university lecturers and managers of health systems) from more than 19 local and international institutions.Conclusions: Master’s classes, free communications and discussions were fruitful and appointment was taken for March 30-31, 2017 in Yaounde (Cameroon)

Nab-PIPAC: a phase IB study protocol of intraperitoneal cisplatin and nab-paclitaxel administered by pressurised intraperitoneal aerosol chemotherapy (PIPAC) in the treatment of advanced malignancies confined to the peritoneal cavity

Introduction: Intraperitoneal dissemination is a major problem resulting in very poor prognosis and a rapid marked deterioration in the quality of life of patients. Pressurised intraperitoneal aerosol chemotherapy (PIPAC) is an emergent laparoscopic procedure aiming to maximise local efficacy and to reduce systemic side effects. Methods and analysis: Nab-PIPAC, a bicentre open-label phase IB, aims to evaluate safety of nab-paclitaxel and cisplatin association using in patients with peritoneal carcinomatosis (PC) of gastric, pancreatic or ovarian origin as ≥1 prior line of systemic therapy. Using a 3+3 design, sequential intraperitoneal laparoscopic application of nab-paclitaxel (7.5, 15, 25, 37.5, 52.5 and 70 mg/m2) and cisplatin (10.5 mg/m2) through a nebuliser to a high-pressure injector at ambient temperature with a maximal upstream pressure of 300 psi. Treatment maintained for 30 min at a pressure of 12 mm Hg and repeated4-6 weeks intervals for three courses total.A total of 6-36 patients are expected, accrual is ongoing. Results are expected in 2024.The primary objective of Nab-PIPAC trial is to assess tolerability and safety of nab-paclitaxel and cisplatin combination administered intraperitoneally by PIPAC in patients with PC of gastric, pancreatic or ovarian origin. This study will determine maximum tolerated dose and provide pharmacokinetic data. Ethic and dissemination: Ethical approval was obtained from the ethical committees of Geneva and Vaud (CCER-2018-01327). The study findings will be published in an open-access, peer-reviewed journal and presented at relevant conferences and research meetings. Trial registration number: NCT04000906.</p