Elevated protein kinase C alpha expression may be predictive of tamoxifen treatment failure

We previously reported that stable transfection of protein kinase C alpha (PKCα) into T47D human breast cancer cells results in tamoxifen (TAM)-resistant tumour growth. Relevance of PKCα expression in clinical specimens was determined by comparing PKCα expression in tumours from patients exhibiting disease recurrence with patients remaining disease-free following TAM treatment. Our results suggest that PKCα expression may predict TAM treatment failure

Stable transfection of protein kinase C alpha cDNA in hormone-dependent breast cancer cell lines

An inverse relationship between protein kinase C (PKC) activity and oestrogen receptor (ER) expression in human breast cell lines and tumours has been firmly established over the past 10 years. To determine whether specific alterations in PKC expression accompany hormone-independence, we examined the expression of PKC isozymes in the hormone-independent human breast cancer cell clones MCF-7 5C and T47D:C42 compared with their hormone-dependent counterparts, MCF-7 A4, MCF-7 WS8 and T47D:A18 respectively. Both hormone-independent cell clones exhibit elevated PKCα expression and increased basal AP-1 activity compared with the hormone-dependent cell clones. To determine whether PKCα overexpression is sufficient to mediate the hormone-independent phenotype, we stably transfected an expression plasmid containing PKCα cDNA to the T47D:A18 and MCF-7 A4 cell lines. This is the first report of PKCα transfection in T47D cells. In contrast to MCF-7 cells, T47D has the propensity to lose the ER and more readily forms tamoxifen-stimulated tumours in athymic mice. We find that in T47D:A18/PKCα clones, there is concomitant up-regulation of PKC βI and δ, whereas in the MCF-7 A4/PKCα transfectants PKC ɛ is up-regulated. In T47D:A18, but not in MCF-7 A4, PKCα stable transfection is accompanied by down-regulation of ER function whilst basal AP-1 activity is elevated. Our results suggest PKCα overexpression may play a role in growth signalling during the shift from hormone dependent to hormone-independent breast cancers. © 2000 Cancer Research Campaig

Chloroviruses have a sweet tooth

Chloroviruses are large double-stranded DNA (dsDNA) viruses that infect certain isolates of chlorella-like green algae. They contain up to approximately 400 protein-encoding genes and 16 transfer RNA (tRNA) genes. This review summarizes the unexpected finding that many of the chlorovirus genes encode proteins involved in manipulating carbohydrates. These include enzymes involved in making extracellular polysaccharides, such as hyaluronan and chitin, enzymes that make nucleotide sugars, such as GDP-L-fucose and GDP-D-rhamnose and enzymes involved in the synthesis of glycans attached to the virus major capsid proteins. This latter process differs from that of all other glycoprotein containing viruses that traditionally use the host endoplasmic reticulum and Golgi machinery to synthesize and transfer the glycans

Prevention and treatment of peri-implant diseases-The EFP S3 level clinical practice guideline.

BACKGROUND: The recently published Clinical Practice Guidelines (CPGs) for the treatment of stages I-IV periodontitis provided evidence-based recommendations for treating periodontitis patients, defined according to the 2018 classification. Peri-implant diseases were also re-defined in the 2018 classification. It is well established that both peri-implant mucositis and peri-implantitis are highly prevalent. In addition, peri-implantitis is particularly challenging to manage and is accompanied by significant morbidity. AIM: To develop an S3 level CPG for the prevention and treatment of peri-implant diseases, focusing on the implementation of interdisciplinary approaches required to prevent the development of peri-implant diseases or their recurrence, and to treat/rehabilitate patients with dental implants following the development of peri-implant diseases. MATERIALS AND METHODS: This S3 level CPG was developed by the European Federation of Periodontology, following methodological guidance from the Association of Scientific Medical Societies in Germany and the Grading of Recommendations Assessment, Development and Evaluation process. A rigorous and transparent process included synthesis of relevant research in 13 specifically commissioned systematic reviews, evaluation of the quality and strength of evidence, formulation of specific recommendations, and a structured consensus process involving leading experts and a broad base of stakeholders. RESULTS: The S3 level CPG for the prevention and treatment of peri-implant diseases culminated in the recommendation for implementation of various different interventions before, during and after implant placement/loading. Prevention of peri-implant diseases should commence when dental implants are planned, surgically placed and prosthetically loaded. Once the implants are loaded and in function, a supportive peri-implant care programme should be structured, including periodical assessment of peri-implant tissue health. If peri-implant mucositis or peri-implantitis are detected, appropriate treatments for their management must be rendered. CONCLUSION: The present S3 level CPG informs clinical practice, health systems, policymakers and, indirectly, the public on the available and most effective modalities to maintain healthy peri-implant tissues, and to manage peri-implant diseases, according to the available evidence at the time of publication

Prevention of breast cancer by recapitulation of pregnancy hormone levels

At the present time, the only approved method of breast cancer prevention is use of the selective estrogen receptor modulator (SERM) tamoxifen. Many breast cancers are driven to grow by estrogen, and tamoxifen exploits this by blocking estrogen action at the estrogen receptor. A counter-intuitive and controversial approach to breast cancer prevention is administration of estrogen and progestin at an early age to achieve pregnancy levels. This approach is supported by the fact that breast cancer incidence is halved by early (≤ 20 years of age) full-term pregnancy. Moreover, it has been demonstrated in rodent models that mimicking the hormonal milieu can effectively prevent carcinogen-induced mammary cancer. In this issue of Breast Cancer Research Rajkumar and colleagues use the rodent model to further define the timing and type of hormonal therapy that is effective in preventing mammary carcinogenesis. Clearly, application of this approach in humans may be difficult, but the potential benefit is intriguing

Expression of caspase-3, p53 and Bcl-2 in generalized aggressive periodontitis

BACKGROUND: Apoptosis, or programmed cell death is a form of physiological cell death. It is increased or decreased in the presence of infection, inflammation or tissue remodelling. Previous studies suggest that apoptosis is involved in the pathogenesis of inflammatory periodontal disease. The aim of the present study was to investigate the clinical features and known indicators of apoptosis (p53, Bcl-2, Caspase-3) in patients with generalized aggressive periodontitis (GAP) METHODS: Eight patients with GAP, who had sites with probing depths (PD) > 5 mm, and 10 periodontally-healthy persons were included in the study. Clinical examinations and PD were performed, and the plaque index and gingival index were recorded. Gingival tissues biopsies were obtained from active site of each patient and from healthy individuals. The expression of caspase-3, Bcl-2, and p53 was evaluated by immunohistochemistry RESULTS: There were no significant differences between GAP and control group with respect to levels of caspase-3 and p53 expression (P > 0.05). Contrary, the frequency of grade 3 expression of Bcl-2 was higher in GAP group than the control group. CONCLUSION: The higher frequency of Bcl-2 expression in GAP group indicates and delayed apoptosis can lead to increasing resident inflammatory cells in periodontal tissues and resulting in progressive periodontal destruction

Extracorporeal CO 2 Removal During Renal Replacement Therapy to Allow Lung-Protective Ventilation in Patients With COVID-19-Associated Acute Respiratory Distress Syndrome

The aim of this retrospective multicenter observational study is to test the feasibility and safety of a combined extracorporeal CO 2 removal (ECCO 2 R) plus renal replacement therapy (RRT) system to use an ultraprotective ventilator setting while maintaining (1) an effective support of renal function and (2) values of pH within the physiologic limits in a cohort of coronavirus infectious disease 2019 (COVID-19) patients. Among COVID-19 patients admitted to the intensive care unit of 9 participating hospitals, 27 patients with acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI) requiring invasive mechanical ventilation undergoing ECCO 2 R-plus-RRT treatment were included in the analysis. The treatment allowed to reduce V T from 6.0 ± 0.6 mL/kg at baseline to 4.8 ± 0.8, 4.6 ± 1.0, and 4.3 ± 0.3 mL/kg, driving pressure (ΔP) from 19.8 ± 2.5 cm H 2 O to 14.8 ± 3.6, 14.38 ± 4.1 and 10.2 ± 1.6 cm H 2 O after 24 hours, 48 hours, and at discontinuation of ECCO 2 R-plus-RRT (T3), respectively ( p < 0.001). PaCO 2 and pH remained stable. Plasma creatinine decreased over the study period from 3.30 ± 1.27 to 1.90 ± 1.30 and 1.27 ± 0.90 mg/dL after 24 and 48 hours of treatment, respectively ( p < 0.01). No patient-related events associated with the extracorporeal system were reported. These data show that in patients with COVID-19-induced ARDS and AKI, ECCO 2 R-plus-RRT is effective in allowing ultraprotective ventilator settings while maintaining an effective support of renal function and values of pH within physiologic limits

Reconstructive periodontal therapy with simultaneous ridge augmentation. A clinical and histological case series report

Treatment of intrabony periodontal defects with a combination of a natural bone mineral (NBM) and guided tissue regeneration (GTR) has been shown to promote periodontal regeneration in intrabony defects. In certain clinical situations, the teeth presenting intrabony defects are located at close vicinity of the resorbed alveolar ridge. In these particular cases, it is of clinical interest to simultaneously reconstruct both the intrabony periodontal defect and the resorbed alveolar ridge, thus allowing insertion of endosseous dental implants. The aim of the present study was to present the clinical and histological results obtained with a new surgical technique designed to simultaneously reconstruct the intrabony defect and the adjacently located resorbed alveolar ridge. Eight patients with chronic advanced periodontitis displaying intrabony defects located in the close vicinity of resorbed alveolar ridges were consecutively enrolled in the study. After local anesthesia, mucoperiosteal flaps were raised, the granulation tissue removed, and the roots meticulously scaled and planed. A subepithelial connective tissue graft was harvested from the palate and sutured to the oral flap. The intrabony defect and the adjacent alveolar ridge were filled with a NBM and subsequently covered with a bioresorbable collagen membrane (GTR). At 11–20 months (mean, 13.9 ± 3.9 months) after surgery, implants were placed, core biopsies retrieved, and histologically evaluated. Mean pocket depth reduction measured 3.8 ± 1.7 mm and mean clinical attachment level gain 4.3 ± 2.2 mm, respectively. Reentry revealed in all cases a complete fill of the intrabony component and a mean additional vertical hard tissue gain of 1.8 ± 1.8 mm. The histologic evaluation indicated that most NBM particles were surrounded by bone. Mean new bone and mean graft area measured 17.8 ± 2.8% and 32.1 ± 8.3%, respectively. Within their limits, the present findings indicate that the described surgical approach may be successfully used in certain clinical cases to simultaneously treat intrabony defects and to reconstruct the resorbed alveolar ridge