Purpose: Radical cystectomy currently remains the standard of care for muscle-invasive bladder cancer. However, surgery can be associated with considerable morbidity and mortality, including the removal of the bladder. An alternative strategy is to preserve the bladder through concurrent chemoradiation following a maximal transurethral resection of the tumor. National protocols using a bladder-preservation approach have demonstrated disease-specific outcomes comparable to radical cystectomy in selected patients, but these results have not been replicated in previously reported population-based series. Here, we describe an outcomes analysis of patients with muscle-invasive bladder cancer treated with either radical surgery or bladder-preserving chemoradiation (BPCRT) for those patients meeting BPCRT criterion using the National Cancer Database (NCDB). Materials and Methods: Using the NCDB, patients with American Joint Commission on Cancer clinical T2-3, N0, M0 urothelial carcinoma diagnosed between 2004 and 2013 were included for analysis. Only patients treated with definitive intent with either radical cystectomy or concurrent chemotherapy and radiation after a maximal transurethral tumor resection were included. Propensity-score matching was used. Results: Among 8454 eligible patients, 7276 (86%) underwent radical cystectomy, and 1178 (14%) underwent BPCRT. Patients undergoing BPCRT were significantly older (median age, 77 vs. 68 y; P
https://ift.tt/2K3cNka
Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Σάββατο 16 Ιουνίου 2018
In-vitro effects of the FS50 protein from salivary glands of Xenopsylla cheopis on voltage-gated sodium channel activity and motility of MDA-MB-231 human breast cancer cells
Voltage-gated sodium channel activity enhances the motility and oncogene expression of metastasic cancer cells that express a neonatal alternatively spliced form of the NaV1.5 isoform. We reported previously that FS50, a salivary protein from Xenopsylla cheopis, showed inhibitory activity against the NaV1.5 channel when assayed in HEK 293T cells and antiarrhythmia effects on rats and monkeys after induction of arrhythmia by BaCl2. This study aims to identify the effect of FS50 on voltage-gated sodium channel activity and the motility of MDA-MB-231 human breast cancer cells in vitro. NaV1.5 was abnormally expressed in the highly metastatic breast cancer cell line MDA-MB-231, but not in the MCF-7 cell line. FS50 significantly inhibited sodium current, migration, and invasion in a dose-dependent manner, but had no effect on the proliferation of MDA-MB-231 cells at the working concentrations (1.5–12 μmol/l) after a long-term treatment for 48 h. Meanwhile, FS50 decreased NaV1.5 mRNA expression without altering the total protein level in MDA-MB-231 cells. Correspondingly, the results also showed that MMP-9 activity and the ratio of MMP-9 mRNA to TIMP-1 mRNA were markedly decreased by FS50. Taken together, our findings highlighted for the first time an inhibitory effect of a salivary protein from a blood-feeding arthropod on breast cancer cells through the NaV1.5 channel. Furthermore, this study provided a new candidate leading molecule against antitumor cells expressing NaV1.5. Correspondence to Xueqing Xu, PhD, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, People's Republic of China Tel: +86 206 164 8537; fax: +86 206 164 8655; e-mail: xu2003@smu.edu.cn Correspondence to Jiguo Wu, PhD, Guangdong Provincial Key Laboratory of Tropical Medicine, Department of Environmental Health, School of Public Health, Southern Medical University, Guangzhou 510515, People's Republic of China Tel: +86 206 164 8327; e-mail: allanjw@126.com Received February 12, 2018 Accepted May 27, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2LZR3mW
https://ift.tt/2LZR3mW
Balanced Crystalloids Versus Saline for Perioperative Intravenous Fluid Administration in Children Undergoing Neurosurgery: A Randomized Clinical Trial
Background: Balanced crystalloid solutions induce less hyperchloremia than normal saline, but their role as primary fluid replacement for children undergoing surgery is unestablished. We hypothesized that balanced crystalloids induce less chloride and metabolic derangements than 0.9% saline solutions in children undergoing brain tumor resection. Methods: In total, 53 patients (age range, 6 mo to 12 y) were randomized to receive balanced crystalloid (balanced group) or 0.9% saline solution (saline group) during and after (for 24 h) brain tumor resection. Serum electrolyte and arterial blood gas analyses were performed at the beginning of surgery (baseline), after surgery, and at postoperative day 1. The primary trial outcome was the absolute difference in serum chloride concentrations (post-preopΔCl−) measured after surgery and at baseline. Secondary outcomes included the post-preopΔ of other electrolytes and base excess (BE); hyperchloremic acidosis incidence; and the brain relaxation score, a 4-point scale evaluated by the surgeon for assessing brain edema. Results: Saline infusion increased post-preopΔCl (6 [3.5; 8.5] mmol/L) compared with balanced crystalloid (0 [−1.0; 3.0] mmol/L; P
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https://ift.tt/2tdD1pJ
Selection of Patients’ Recumbent Position Laterality According to Physician Handedness Bias Increases the Success Rate of Lumbar Puncture: A Multicenter Study
Background: Lumbar puncture (LP) is a medical procedure required during spinal anesthesia and for obtaining cerebrospinal fluid samples in the diagnosis of neurological disorders. The aim of this study was to assess the effects of physicians' handedness bias and the laterality of patients' recumbent position on the success rate of LPs. Methods and Patients: A prospective multicenter study including 36 physicians (18 left-handed and 18 right-handed) and 7200 patients was conducted in 6 medical centers. In each center, 1200 patients were randomized into group L (LPs performed by left-handed physicians) or group R (LPs performed by right-handed physicians). Each physician performed 200 cases of LPs, of which the laterality of the recumbent position (either on the left or right side) was decided after a second randomization. A successful LP was considered when the free flow of cerebrospinal fluid was observed upon the first attempt. Results: There was no significant difference in patient characteristics between groups L and R. Right-handed physicians had a significantly higher LP success rate with patients in the left lateral recumbent position (LRP) (1595/1800 vs. 1408/1800; odds ratio, 0.539; 95% confidence interval, 0.348-0.836; P=0.006). For left-handed physicians, the LP success rate was higher when patients were in the right LRP (1424/1800 vs. 1593/1800, odds ratio, 0.449; 95% confidence interval, 0.283-0.711; P=0.001). Patients' age, sex, height, and weight were not statistically related to LP success during multivariate analyses. Conclusions: Physicians handedness bias and patient laterality of recumbent position affects the success of LPs. Right-handed physicians have a greater chance of performing successful LPs when patients are in the left LRP, and vice versa. J.-L.Z. and Y.-R.S. contributed equally. Supported by the National Natural Science Foundation of China (81471241, 81271375, and 81171133), Shanghai Municipal Science and Technology Commission project (16411955300, 18441903300 and 18695841300), and Shanghai Minhang Natural Science Foundation (2014MHZ001). The authors have no conflicts of interest to disclose. Address correspondence to: Jin Hu, MD, PhD, Department of Neurosurgery, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, P.R. China (e-mail: 286644104@qq.com). Received January 7, 2018 Accepted May 8, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved
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https://ift.tt/2MuIWQ2
Overcoming heparin resistance in pregnant women with antithrombin deficiency: a case report and review of the literature
The risk of thromboembolic events during pregnancy in patients with antithrombin deficiency is increased. Preventing thromboembolic events during pregnancy in the case of antithrombin deficiency is still a mat...
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Clinical feasibility and positional stability of an implanted wired transmitter in a novel electromagnetic positioning system for prostate cancer radiotherapy
Three aspects of the RayPilot real-time tracking system were investigated: (1) feasibility of the transmitter with respect to implantation and explantation procedures, (2) user and patients' experiences and (3) quantification of the transmitter positional stability in relation to fiducial markers.
https://ift.tt/2JIXL43
Changing the global radiation therapy paradigm
Filling the gap in cancer care in underserved regions worldwide requires global collaboration and concerted effort to share creative ideas, pool talents and develop sustainable support from governments, industry, academia and non-governmental organizations. Comprehensive cancer care, which fits within and strengthens the broader healthcare system, ranges from prevention to screening, to curative treatment, to palliative care and to long-term follow-up. Radiation therapy is an essential component for curative and palliative cancer care and can serve as a stable focal point physically and for personnel around which regional cancer and health care programs can be established.
https://ift.tt/2LVV0st
Hyperthermia in cervical cancer – current status
Publication date: Available online 15 June 2018
Source:Reports of Practical Oncology & Radiotherapy
Author(s): Ewa Burchardt, Andrzej Roszak
BackgroundThis article reviews the salient features of recent results of clinical studies. It puts a special emphasis on technical aspects, mechanisms of action together with radiotherapy and chemotherapy and points out areas for additional investigation.AimTo present the current state of knowledge on hyperthermia (HT) and to highlight its role in the treatment of cervical cancer.Materials and methodsThe literature on the clinical use of combined hyperthermia for cervical cancer was analyzed. Clinical outcomes together with the technical aspects and the role of HT were also evaluated.ResultsClinically randomized trials have demonstrated benefit including survival with the addition of hyperthermia to radiation or chemotherapy in the treatment of cervical cancer without significant acute or late morbidities. The technological advances have led to an effective and safer treatment delivery, thermal treatment planning, thermal dose monitoring and online adaptive temperature modulation.ConclusionsDue to rapid development over the last decade of hyperthermia systems and new studies at the basic science and clinical level, the perception of hyperthermia as a part of multimodality treatment in cervical cancer has been changed. However, there is still a need for multicentre randomized clinical trials.
https://ift.tt/2JNGYbQ
Novel Common Genetic Susceptibility Loci for Colorectal Cancer
Abstract
Background
Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10−8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. Methods
We conducted a GWAS in European descent CRC cases and control subjects using a discovery–replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10−8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. Results
The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10−8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. Conclusions
This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.https://ift.tt/2tfaUX8
Cancers, Vol. 10, Pages 206: Constitutive Activation of STAT3 in Myeloma Cells Cultured in a Three-Dimensional, Reconstructed Bone Marrow Model
Cancers, Vol. 10, Pages 206: Constitutive Activation of STAT3 in Myeloma Cells Cultured in a Three-Dimensional, Reconstructed Bone Marrow Model
Cancers doi: 10.3390/cancers10060206
Authors: Yung-Hsing Huang Ommoleila Molavi Abdulraheem Alshareef Moinul Haque Qian Wang Michael P. Chu Christopher P. Venner Irwindeep Sandhu Anthea C. Peters Afsaneh Lavasanifar Raymond Lai
Malignant cells cultured in three-dimensional (3D) models have been found to be phenotypically and biochemically different from their counterparts cultured conventionally. Since most of these studies employed solid tumor types, how 3D culture affects multiple myeloma (MM) cells is not well understood. Here, we compared MM cells (U266 and RPMI8226) in a 3D culture model with those in conventional culture. While the conventionally cultured cells were present in single cells or small clusters, MM-3D cells grew in large spheroids. We discovered that STAT3 was the pathway that was more activated in 3D in both cell lines. The active form of STAT3 (phospho-STAT3 or pSTAT3), which was absent in MM cells cultured conventionally, became detectable after 1–2 days in 3D culture. This elevated pSTAT3 level was dependent on the 3D environment, since it disappeared after transferring to conventional culture. STAT3 inhibition using a pharmacological agent, Stattic, significantly decreased the cell viability of MM cells and sensitized them to bortezomib in 3D culture. Using an oligonucleotide array, we found that 3D culture significantly increased the expression of several known STAT3 downstream genes implicated in oncogenesis. Since most primary MM tumors are naturally STAT3-active, studies of MM in 3D culture can generate results that are more representative of the disease.
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Switch maintenance therapy with docetaxel and bevacizumab after induction therapy with cisplatin, pemetrexed, and bevacizumab in advanced non-squamous non-small cell lung cancer: a phase II study
Abstract
Switch maintenance therapy, using alternative agents that were not administered during induction chemotherapy, is a treatment option for advanced non-squamous non-small cell lung cancer (NSCLC). Bevacizumab is known to increase the efficacy of other chemotherapeutic agents; however, switch maintenance therapy with docetaxel and bevacizumab has not been adequately studied. The goal of this study was to evaluate the efficacy and safety of switch maintenance therapy with docetaxel and bevacizumab following induction therapy with cisplatin, pemetrexed, and bevacizumab. Chemotherapy-naïve non-squamous NSCLC patients received induction therapy of four cycles of cisplatin (75 mg/m2), pemetrexed (500 mg/m2), and bevacizumab (15 mg/kg). Patients who achieved disease control after induction therapy then received maintenance therapy with docetaxel (50 mg/m2) and bevacizumab (15 mg/kg) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival from enrollment. This study enrolled 49 NSCLC patients, among which 38 (77.6%) completed the four cycles of induction therapy and received maintenance therapy. The median progression-free survival from enrollment was 7.8 months (95% confidence interval: 4.7–11.0 months). The most common toxicities of grade 3 or higher were neutropenia (68.4%), leukopenia (50.0%), febrile neutropenia (31.8%), and hypertension. Switch maintenance therapy with docetaxel and bevacizumab following induction therapy with cisplatin, pemetrexed, and bevacizumab demonstrated modest efficacy and frequent hematologic toxicity in non-squamous NSCLC patients.
https://ift.tt/2JI9srE
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