Activation of RhoA,B,C by Yersinia Cytotoxic Necrotizing Factor (CNFy) Induces Apoptosis in LNCaP Prostate Cancer Cells

Prostate cancer is the most common malignancy, accounting for about 25% of all incident cases among men in industrialized countries. The human androgen-dependent prostate cancer cell line LNCaP, which is derived from a metastatic lesion of human prostatic adenocarcinoma, is frequently used to study prostate cancer associated signaling pathways in vitro. Recently it was described that Rho GTPase activation in these cells leads to apoptotic responses. We used the bacterial toxins CNFy and CNF1, which specifically and directly activate Rho GTPases by deamidation of a single glutamine. We asked whether these Rho activators could induce apoptosis in LNCaP cells. Our results indicate that RhoA activation, induced by CNFy, does lead to intrinsic apoptosis of the cells. Analysis of the underlying signaling pathway reveals that apoptosis induction requires the activity of Rho kinase (ROCK) and myosin activation, an apoptotic pathway previously identified in cancer stem cells.     

Common Carotid Artery Flow Measured by 3-D Ultrasonic Vector Flow Imaging and Validated with Magnetic Resonance Imaging

Ultrasound (US) examination of the common carotid artery was compared with a through-plane magnetic resonance imaging (MRI) sequence to validate a recently proposed technique for 3-D US vector flow imaging. Data from the first volunteer examined were used as the training set, before volume flow and peak velocities were calculated for the remaining eight volunteers. Peak systolic velocities (PSVs) and volume flow obtained with 3-D US were, on average, 34% higher and 24% lower than those obtained with MRI, respectively. A high correlation was observed for PSV (r = 0.79), whereas a lower correlation was observed for volume flow (r = 0.43). The overall standard deviations were ±5.7% and ±5.7% for volume flow and PSV with 3-D US, compared with ±2.7% and ±3.2% for MRI. Finally, the data were re-processed with a change in the parameter settings for the echo-canceling filter to investigate its influence on overall performance. PSV was less affected by the re-processing, whereas the difference in volume flow between 3-D vector flow imaging and MRI was reduced to ?9%, and with an improved overall standard deviation of ±4.7%. The results illustrate the feasibility of using 3-D US for precise and angle-independent volume flow and PSV estimation in vivo.     

Brain metastases in patients under 50?years of age: retrospective analysis

Several previous publications suggested that younger patients with brain metastases have longer survival than older patients. However, detailed studies of younger patient groups are scarce. Therefore, a multi-institutional analysis of younger patients with brain metastases was performed (defined as adults with age <50?years). Prognostic factors for survival were examined by uni- and multivariate analyses and compared to those obtained in patients with age ??50?years. Multivariate analysis of 106 patients (median age 44?years, range 23?C49?years) revealed three independent prognostic factors for survival: performance status, extracranial metastases and primary tumor control. Survival was significantly better in patients treated after the year 2000 (median 9.4?months) as compared to those treated before the year 2000 (median 5.1?months, p?=?0.04). This improvement appeared to be related to an increased use of surgery or radiosurgery (SRS) and decreasing numbers of patients with uncontrolled primary tumor. Irrespective of management approach, survival beyond 5?years was uncommon (actuarial rate 6?%; 17?% in patients treated with upfront surgery or SRS). In conclusion, more intense multidisciplinary approaches aiming at control both in the brain, extracranial metastatic sites, and primary tumor site might have contributed to gradual survival improvements in recent years. Nevertheless, further efforts are necessary to improve long-term survival.     

Subtyping of intraductal papillary mucinous neoplasms – pitfalls of MUC1 immunohistochemistry

Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions of pancreatic ductal adenocarcinoma (PDAC). Current edition of WHO Classification of Tumors of the Digestive System recognizes four different subtypes (gastric, intestinal, pancreatobiliary, and oncocytic) and recommends analysis of mucin expression (MUC1, MUC2, MUC5AC, MUC6) as well as evaluation of architectural and cell differentiation patterns for correct classification. However, there is no consensus on MUC1 expression of IPMN‐lesions in the literature. Current recommendations are based on studies where antibodies against the core MUC1 protein or sialylated MUC1 (tumor associated MUC1), not the fully glycosylated MUC1 were used. We have recently reported that MUC1 is strongly expressed in both gastric and intestinal types IPMN specimens from the cystic wall, obtained by endoscopic ultrasound guided microbiopsy procedure. We have used a commercial MUC1 antibody, validated and recommended for diagnostic use, which recognizes fully glycosylated MUC1. Based on the above, we propose a revision of the WHO Classification, specifying that antibodies against tumor associated MUC1 should be used for IPMN subtyping.     

Superior fixation and less periprosthetic stress-shielding of tibial components with a finned stem versus an I-beam block stem: a randomized RSA and DXA study with minimum 5 years’ follow-up

Background and purpose — The stem on the tibial component of total knee arthroplasty provides mechanical resistance to lift-off, shear forces, and torque. We compared tibial components with finned stems (FS) and I-beam block stems (IS) to assess differences in implant migration.

Patients and methods — In a patient-blinded RCT, 54 patients/knees (15 men) with knee osteoarthritis at a mean age of 77 years (70–90) were randomly allocated to receive tibial components with either a FS (n = 27) or an IS (n = 27). Through 5 to 7 years’ follow-up, implant migration was measured with RSA, periprosthetic bone mineral density (BMD) was measured with DXA, and surgeons reported American Knee Society Score (AKSS).

Results — At minimum 5 years’ follow-up, maximum total point motion (MTPM) was higher (p = 0.04) for IS (1.48?mm, 95% CI 0.81–2.16) than for FS (0.85?mm, CI 0.38–1.32) tibial components. Likewise, total rotation (TR) was higher (p = 0.03) for IS (1.51?, CI 0.78–2.24) than for FS (0.81?, CI 0.36–1.27). Tibial components with IS externally rotated 0.50° (CI –0.06 to 1.06) while FS internally rotated 0.09° (CI –0.20 to 0.38) (p = 0.03). Periprosthetic bone stress-shielding was higher (p < 0.01) up to 2 years’ follow-up for IS compared with FS in the regions medial to the stem (–13% vs. –2%) and posterior to the stem (–13% vs. –2%). Below the stem bone loss was also higher (p = 0.01) for IS compared with FS (–6% vs. +1%) up to 1-year follow-up. Knee score improved similarly in both groups up to 5 years’ follow-up.

Interpretation — Periprosthetic bone stress-shielding medial and posterior to the stem until 2 years, and tibial component migration at 5 years, was less for a finned compared with an I-shaped block stem design.

Trial registration: ClinicalTrials.gov identifier: NCT00175136.