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Frontiers in Medicinal Chemistry 2017 in Bern, Switzerland.
ChemMedChem. 2017 Oct 09;12(19):1645-1651
Authors: Probst D, Heitz M, Poirier M, Gan BH, Delalande C, Reymond JL
Abstract
Sharing capital ideas: The 2017 Frontiers in Medicinal Chemistry (FiMC) conference, organized jointly by the German Chemical Society, the German Pharmaceutical Society, and the Swiss Chemical Society, was held at the Department of Chemistry and Biochemistry of the University of Bern in February 2017. Herein we summarize the many conference highlights, and look forward to the next FiMC meeting, to be held in Jena (Germany) in March 2018.
PMID: 28941184 [PubMed - indexed for MEDLINE]
Related Articles |
CRISPR-Cas9: From a bacterial immune system to genome-edited human cells in clinical trials.
Bioengineered. 2017 May 04;8(3):280-286
Authors: Kick L, Kirchner M, Schneider S
Abstract
The adaptive bacterial immune system CRISPR-Cas is revolutionizing all fields of life science and has opened up new frontiers toward personalised medicine. Since the elucidation of the molecular mechanism of Cas9 from Streptococcus pyogenes in 2012 and its development as a genomic engineering tool, genetic modifications in more than 40 species have been performed, over 290 patents have been filed worldwide and the first clinical trials using CRISPR-Cas-modified T-cells have recently been started in China and in the US. In this review we summarise current design developments, novel Cas systems and their antagonists, present and potential future applications as well as the ongoing debate on ethical issues, which has arisen through the CRISPR-Cas technology.
PMID: 28287876 [PubMed - indexed for MEDLINE]
22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
"Zhonghua Yi Xue Za Zhi"[jour]
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36 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
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PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Diagnostic significance of serum periostin in eosinophilic chronic sinusitis with nasal polyps.
Acta Otolaryngol. 2017 Oct 28;:1-5
Authors: Xu M, Zhang W, Chen D, Zhou H, Chen L
Abstract
OBJECTIVES: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease. Eosinophilic CRSwNP (ENP) exhibits a strong tendency for recurrence after surgery. Given that the treatment strategy of ENP differs from that of non-eosinophilic CRSwNP (nENP), clinical diagnostic criteria that distinguish ENP from nENP are needed.
METHODS: In total, 94 CRSwNP patients were enrolled in the cohort. Factors associated with ENP were determined with regression analysis, and optimal cutoff points of the predictors were determined by a receiver operating characteristic curve.
RESULTS: Serum periostin levels, blood eosinophils and basophils counts significantly differed between ENP and nENP. A combination of the cut-off values for the three predictors, including absolute blood eosinophil and basophil counts, yielded a sensitivity of 79.2% and 70.8%, and a specificity of 84.8% and 73.9%, respectively. Serum periostin levels yielded a sensitivity of 72.9% and a specificity of 60.9% for the diagnosis of ENP. The predicted probability of periostin in combination with blood eosinophils and basophils counts (AUC, 0.872) exhibited moderate accuracy. In addition, patients with ENP displayed an increased prevalence of smoking.
CONCLUSIONS: Periostin in combination with blood eosinophils and basophils counts has the potential to better refine current CRSwNP phenotypes.
PMID: 29081260 [PubMed - as supplied by publisher]
21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2017/10/31
PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
How efficient are rodent models for Alzheimer's disease drug discovery?
Expert Opin Drug Discov. 2017 Oct 30;:
Authors: Guo B, Zhou Q
PMID: 29082769 [PubMed - as supplied by publisher]
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upper respiratory tract infection
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PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Design and Evaluation of Mucoadhesive Vaginal Tablets of Tenofovir Disoproxil Fumarate for Pre-Exposure Prophylaxis of HIV.
Drug Dev Ind Pharm. 2017 Oct 30;:1-44
Authors: Khan AB, Thakur RS
Abstract
OBJECTIVE: To design and evaluate novel, feasible, safe, mucoadhesive intravaginal tablets of tenofovir disoproxil fumarate (TDF).
SIGNIFICANCE: It may provide pre-exposure prophylaxis for women against HIV.
METHODS: TDF intravaginal tablets were formulated employing poylvinylpyrrolidone (PVP) as the matrix forming polymer and various mucoadhesive polymers such as carbopol 934, 940, chitosan, and sodium carboxymethylcellulose (SCMC). Wet granulation was used. The evaluation involved testing drug-excipient compatibility, precompression parameters such as percentage yield, bulk density and tapped density of the granules, Carr's index, Hausner ratio, angle of repose, post compression parameters such as colour, shape, physical dimensions, weight variation, hardness, friability, swelling index, assay, in vitro dissolution study and ex vivo mucoadhesion studies.
RESULTS: Based on in vitro evaluation, C1 was selected as the best formulation and evaluated further for release kinetics, curve fitting analysis, absorption studies using liquid chromatography-mass spectrometry (LC-MS) technique and histopathological assessment in female Sprague-Dawley rats. C1 followed Higuchi model kinetics. Accelerated stability study was as per ICH guidelines by keeping C1 at 40 ± 2°C and 75 ± 5% RH for six months.
CONCLUSIONS: C1 was selected as the best formulation due to better swelling index (65.93% at 24 h), prolonged release of 100.62% cumulative drug release (CDR) at 24 h, superior mucoadhesion force (35.93 × 10(2) dynes/cm(2)) and retention time (16 h). The study revealed that C1 remained stable for six months. C1 showed nil systemic absorption which is desirable and according to histopathological study, C1, exhibited minimal damage on the rat vaginal epithelium indicating safety.
PMID: 29082767 [PubMed - as supplied by publisher]
Application of scCO2 technology for preparing CoQ10 solid dispersion and SFC-MS/MS for analyzing in vivo bioavailability.
Drug Dev Ind Pharm. 2017 Oct 30;:1-7
Authors: Yang R, Li Y, Li J, Liu C, Du P, Zhang T
Abstract
OBJECTIVE: In this study, solid dispersion (SD) for oral delivery of a poorly water-soluble drug, coenzyme Q10 was developed by supercritical fluid technology and characterized in vitro and in vivo.
METHODS: Dissolution was used to optimize the formulations of CoQ10-SD. The physicochemical properties of SD were investigated by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The supercritical fluid chromatography-electrospray ionization tandem mass spectrometry (SFC-ESI-MS/MS) was used for the in vivo study.
RESULTS: The results of DSC and PXRD indicated that the drug in SD was in amorphous state. In vitro drug release, the dissolution of coenzyme Q10 in solid dispersion improved to 78.8% compared with commercial tablets of 0.16%. The area under c-t curve (AUC0-72h) and mean maximum concentrations (Cmax) of CoQ10-SD were 2.43-fold and 3.0-fold, respectively higher than that of commercial tablets in rats, confirming improved bioavailability.
CONCLUSION: Supercritical fluid technology was successfully used for the preparation and analysis of CoQ10-SD for the first time and significantly improved the dissolution and bioavailability of coenzyme Q10.
PMID: 29082762 [PubMed - as supplied by publisher]
Effect of Modified Shaker Exercise on the Amplitude and Duration of Swallowing Sounds: Evidence from Cervical Auscultation.
Rehabil Res Pract. 2017;2017:6526214
Authors: Babu S, Balasubramaniam RK, Varghese A
Abstract
OBJECTIVE: Anecdotal evidence shows that the Shaker exercise and its modifications improve pharyngeal muscle contraction. However, there is no experimental evidence for the same. Thus, the present study examined the effect of modified Shaker exercise on the amplitude and duration of pharyngeal muscle contraction using cervical auscultation.
DESIGN: The study follows a cross-sectional study design, where 50 healthy individuals (23 males and 27 females) performed modified Shaker exercise and noneffortful swallow during 10 ml water swallowing. Swallow sound characteristics were analyzed with and without modified Shaker exercise using cervical auscultation.
RESULTS: The results of mixed ANOVA revealed significant differences for the amplitude of swallow sound with modified Shaker exercise (mean = 47.24, SD = 20.64) when compared to noneffortful swallow (mean = 28.19, SD = 10.26) at p < 0.05. However, no significant difference was obtained for the swallow sound duration with (mean = 0.19, SD = 0.07) and without (mean = 0.18, SD = 0.07) modified Shaker exercise at p > 0.05. No significant difference across the genders was also noted at p > 0.05.
CONCLUSION: The outcomes of the study suggest that modified Shaker exercise improves the amplitude of pharyngeal muscle contraction. Further studies are needed to confirm this finding using gold standard tools like videofluoroscopy.
PMID: 29082044 [PubMed]
Diagnostic significance of serum periostin in eosinophilic chronic sinusitis with nasal polyps.
Acta Otolaryngol. 2017 Oct 28;:1-5
Authors: Xu M, Zhang W, Chen D, Zhou H, Chen L
Abstract
OBJECTIVES: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease. Eosinophilic CRSwNP (ENP) exhibits a strong tendency for recurrence after surgery. Given that the treatment strategy of ENP differs from that of non-eosinophilic CRSwNP (nENP), clinical diagnostic criteria that distinguish ENP from nENP are needed.
METHODS: In total, 94 CRSwNP patients were enrolled in the cohort. Factors associated with ENP were determined with regression analysis, and optimal cutoff points of the predictors were determined by a receiver operating characteristic curve.
RESULTS: Serum periostin levels, blood eosinophils and basophils counts significantly differed between ENP and nENP. A combination of the cut-off values for the three predictors, including absolute blood eosinophil and basophil counts, yielded a sensitivity of 79.2% and 70.8%, and a specificity of 84.8% and 73.9%, respectively. Serum periostin levels yielded a sensitivity of 72.9% and a specificity of 60.9% for the diagnosis of ENP. The predicted probability of periostin in combination with blood eosinophils and basophils counts (AUC, 0.872) exhibited moderate accuracy. In addition, patients with ENP displayed an increased prevalence of smoking.
CONCLUSIONS: Periostin in combination with blood eosinophils and basophils counts has the potential to better refine current CRSwNP phenotypes.
PMID: 29081260 [PubMed - as supplied by publisher]
Prenatal and/or postnatal high-fat diet alters testicular parameters in adult Wistar Albino rats.
Histol Histopathol. 2017 Oct 30;:11941
Authors: Campos-Silva P, Costa WS, Sampaio FJB, Gregorio BM
Abstract
Here, we evaluated the effects of a high-fat diet during the prenatal and/or postnatal period on the metabolic parameters and testes of 4-month-old Wistar rats. The experimental groups, composed of male Wistar rats, were: C/C (n=8), HF/HF (n=8) (pups with the same diet as their dams, after weaning), C/HF (n=8), and HF/C (n=9) (pups with a different diet after weaning, from that of their dams). The biometric parameters, blood glucose levels, serum levels, the gonadosomatic index, sperm parameters, testes, and genital fat deposits were evaluated. The HDL-c serum levels were significantly lower in the C/HF group (P=0.0100), whereas animals in the HF/C group presented hypertriglyceridemia (P=0.0005). The sperm concentration was lower in the HF/HF group than in the HF/C group (P=0.0072), and sperm viability was lower in all groups receiving a high-fat diet (P<0.0001). The tubular compartment was the smallest in the HF/HF group (P<0.0001). The diameter of the seminiferous tubule was the widest in the HF/C group (P<0.0001). The height of the seminiferous epithelium in all groups was lower than that in the C/C group (PP<0.0001). Testosterone and steroidogenic acute regulatory protein (STAR) expression levels were lower in the C/HF group (P=0.0218 and P=0.0215, respectively). The HF diet, regardless of the administration period, induced a limited number of metabolic changes, and modifications in the histoarchitecture of the testes and sperm parameters. These data suggest that a HF diet may cause disturbances in spermatogenesis and fertility impairment in adulthood.
PMID: 29083015 [PubMed - as supplied by publisher]
Prenatal and/or postnatal high-fat diet alters testicular parameters in adult Wistar Albino rats.
Histol Histopathol. 2017 Oct 30;:11941
Authors: Campos-Silva P, Costa WS, Sampaio FJB, Gregorio BM
Abstract
Here, we evaluated the effects of a high-fat diet during the prenatal and/or postnatal period on the metabolic parameters and testes of 4-month-old Wistar rats. The experimental groups, composed of male Wistar rats, were: C/C (n=8), HF/HF (n=8) (pups with the same diet as their dams, after weaning), C/HF (n=8), and HF/C (n=9) (pups with a different diet after weaning, from that of their dams). The biometric parameters, blood glucose levels, serum levels, the gonadosomatic index, sperm parameters, testes, and genital fat deposits were evaluated. The HDL-c serum levels were significantly lower in the C/HF group (P=0.0100), whereas animals in the HF/C group presented hypertriglyceridemia (P=0.0005). The sperm concentration was lower in the HF/HF group than in the HF/C group (P=0.0072), and sperm viability was lower in all groups receiving a high-fat diet (P<0.0001). The tubular compartment was the smallest in the HF/HF group (P<0.0001). The diameter of the seminiferous tubule was the widest in the HF/C group (P<0.0001). The height of the seminiferous epithelium in all groups was lower than that in the C/C group (PP<0.0001). Testosterone and steroidogenic acute regulatory protein (STAR) expression levels were lower in the C/HF group (P=0.0218 and P=0.0215, respectively). The HF diet, regardless of the administration period, induced a limited number of metabolic changes, and modifications in the histoarchitecture of the testes and sperm parameters. These data suggest that a HF diet may cause disturbances in spermatogenesis and fertility impairment in adulthood.
PMID: 29083015 [PubMed - as supplied by publisher]
Related Articles |
Maturation of auditory neural processes in autism spectrum disorder - A longitudinal MEG study.
Neuroimage Clin. 2016;11:566-77
Authors: Port RG, Edgar JC, Ku M, Bloy L, Murray R, Blaskey L, Levy SE, Roberts TP
Abstract
BACKGROUND: Individuals with autism spectrum disorder (ASD) show atypical brain activity, perhaps due to delayed maturation. Previous studies examining the maturation of auditory electrophysiological activity have been limited due to their use of cross-sectional designs. The present study took a first step in examining magnetoencephalography (MEG) evidence of abnormal auditory response maturation in ASD via the use of a longitudinal design.
METHODS: Initially recruited for a previous study, 27 children with ASD and nine typically developing (TD) children, aged 6- to 11-years-old, were re-recruited two to five years later. At both timepoints, MEG data were obtained while participants passively listened to sinusoidal pure-tones. Bilateral primary/secondary auditory cortex time domain (100 ms evoked response latency (M100)) and spectrotemporal measures (gamma-band power and inter-trial coherence (ITC)) were examined. MEG measures were also qualitatively examined for five children who exhibited "optimal outcome", participants who were initially on spectrum, but no longer met diagnostic criteria at follow-up.
RESULTS: M100 latencies were delayed in ASD versus TD at the initial exam (~ 19 ms) and at follow-up (~ 18 ms). At both exams, M100 latencies were associated with clinical ASD severity. In addition, gamma-band evoked power and ITC were reduced in ASD versus TD. M100 latency and gamma-band maturation rates did not differ between ASD and TD. Of note, the cohort of five children that demonstrated "optimal outcome" additionally exhibited M100 latency and gamma-band activity mean values in-between TD and ASD at both timepoints. Though justifying only qualitative interpretation, these "optimal outcome" related data are presented here to motivate future studies.
CONCLUSIONS: Children with ASD showed perturbed auditory cortex neural activity, as evidenced by M100 latency delays as well as reduced transient gamma-band activity. Despite evidence for maturation of these responses in ASD, the neural abnormalities in ASD persisted across time. Of note, data from the five children whom demonstrated "optimal outcome" qualitatively suggest that such clinical improvements may be associated with auditory brain responses intermediate between TD and ASD. These "optimal outcome" related results are not statistically significant though, likely due to the low sample size of this cohort, and to be expected as a result of the relatively low proportion of "optimal outcome" in the ASD population. Thus, further investigations with larger cohorts are needed to determine if the above auditory response phenotypes have prognostic utility, predictive of clinical outcome.
PMID: 27158589 [PubMed - indexed for MEDLINE]
Related Articles |
Effects of light wavelength on MEG ERD/ERS during a working memory task.
Int J Psychophysiol. 2016 Jun;104:10-6
Authors: Okamoto Y, Nakagawa S
Abstract
We investigated the effects of light wavelengths on cortical oscillatory activity associated with working memory processes. Cortical activity responses were measured using magnetoencephalography (MEG) while participants performed an auditory Sternberg memory task during exposure to light of different wavelength. Each trial of the memory task consisted of four words presented as a memory set and one word presented as a probe. All words were presented audibly. Participants were instructed to indicate whether the probe word was or was not presented within the memory set. A total of 90 trials were conducted under the light exposure. Event-related synchronization (ERS) and event-related desynchronization responses in the alpha frequency range during the task were analyzed. Results showed that, during memory encoding, ERS responses were significantly greater in the short-wavelength (blue) light condition than in the middle-wavelength (green) light condition, approximately 20-30min after the onset of light exposure. Behavioral performance was very high throughout the experiment and there was no difference between the light conditions. Although the light effects were not observed in behavior, the result of ERS suggests that 20-30min of exposure to blue light enhances cortical activity related to active memory maintenance and/or attention to auditory stimuli.
PMID: 27040560 [PubMed - indexed for MEDLINE]
Related Articles |
Event-related oscillations (ERO) during an active discrimination task: Effects of lesions of the nucleus basalis magnocellularis.
Int J Psychophysiol. 2016 May;103:53-61
Authors: Sanchez-Alavez M, Ehlers CL
Abstract
The cholinergic system in the brain is involved in attentional processes that are engaged for the identification and selection of relevant information in the environment and the formation of new stimulus associations. In the present study we determined the effects of cholinergic lesions of nucleus basalis magnocellularis (NBM) on amplitude and phase characteristics of event related oscillations (EROs) generated in an auditory active discrimination task in rats. Rats were trained to press a lever to begin a series of 1kHz tones and to release the lever upon hearing a 2kHz tone. A time-frequency based representation was used to determine ERO energy and phase synchronization (phase lock index, PLI) across trials, recorded within frontal cortical structures. Lesions in NBM produced by an infusion of a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) resulted in (1) a reduction of the number of correct behavioral responses in the active discrimination task, (2) an increase in ERO energy in the delta frequency bands, (3) an increase in theta, alpha and beta ERO energy in the N1, P3a and P3b regions of interest (ROI), and (4) an increase in PLI in the theta frequency band in the N1 ROIs. These studies suggest that the NBM cholinergic system is involved in maintaining the synchronization/phase resetting of oscillations in different frequencies in response to the presentation of the target stimuli in an active discrimination task.
PMID: 25660307 [PubMed - indexed for MEDLINE]
Deep Vein Thrombosis Complicated by Spontaneous Iliopsoas Hematoma in Patient with Septic Shock.
Am J Case Rep. 2017 Oct 30;18:1148-1152
Authors: Butt MU, Buzsaki LA, Smyth SS, Elayi SC
Abstract
BACKGROUND Spontaneous retroperitoneal hemorrhage (SRH) is a rare and difficult-to-diagnose entity. It is not associated with trauma, pathology, or iatrogenic manipulations. Few cases have been reported, with the only precipitating factor recognized being bleeding diatheses such as anticoagulation states, inherited coagulopathies, and hemodialysis. However, none of these have been described in combination with septic shock, which itself is associated with platelet dysfunction, coagulation dysfunction, and vasculopathy. CASE REPORT Our case involves an elderly man presenting with altered mental status of unknown etiology, in addition to hemodynamic instability, presumably due to septic shock, without any overt signs of bleeding. After his initial exam revealed lower-extremity edema and decubitus ulcers, a venous Doppler was performed, which revealed extensive deep vein thrombosis. It was unknown whether the sepsis or DVT occurred first. Therapeutic anticoagulation with heparin was subsequently started. On hospital day 4, a CT abdomen with contrast identified retroperitoneal hematoma after the patient's hemoglobin lowered without any overt signs of bleeding. The diagnosis of spontaneous retroperitoneal hematoma was one of exclusion and posed a therapeutic dilemma (conservative versus invasive management). CONCLUSIONS Sepsis-related coagulopathy and heparin use in an elderly patient predisposed him to an iliopsoas hematoma. In this case, conservative management with reversal of anticoagulation and blood transfusion was sufficient to stabilize the patient.
PMID: 29081491 [PubMed - in process]
Assessing hearing loss self-management in older adults.
Int J Audiol. 2017 Oct 28;:1-8
Authors: Convery E, Meyer C, Keidser G, Hickson L
Abstract
OBJECTIVE: To evaluate the capacity of a self-management assessment tool to identify unmet hearing health care (HHC) needs; to determine whether such an assessment yields novel and clinically useful information.
DESIGN: Hearing loss self-management (HLSM) was assessed with the Partners in Health scale and the Cue and Response interview from the Flinders Chronic Condition Management Program™. The results of the scale and the interview were compared to determine the extent to which they each contributed to the assessment of HLSM.
STUDY SAMPLE: Thirty older adults who currently receive HHC.
RESULTS: The two assessment tools were useful in identifying the specific domains in which participants lacked good HLSM skills. While participants tended to have a high level of knowledge about hearing loss and technology-based interventions, many reported the presence of unmet psychosocial needs with no clear plan for addressing them. There was considerable variation in terms of the extent to which their audiologists facilitated shared decision-making.
CONCLUSIONS: The results suggest that HLSM has the potential to play an important role in audiological rehabilitation. A HLSM assessment tool that more precisely matches the unique needs of people with hearing loss should be developed, along with interventions to meet those needs.
PMID: 29081257 [PubMed - as supplied by publisher]
Related Articles |
Long non-coding RNA MALAT-1 modulates metastatic potential of tongue squamous cell carcinomas partially through the regulation of small proline rich proteins.
BMC Cancer. 2016 Sep 01;16:706
Authors: Fang Z, Zhang S, Wang Y, Shen S, Wang F, Hao Y, Li Y, Zhang B, Zhou Y, Yang H
Abstract
BACKGROUND: We previously described several abnormally expressed long non-coding RNA (lncRNA) in tong squamous cell carcinomas (TSCCs) that might be associated with tumor progression. In the present study, we aimed to investigate the role of abnormally expressed metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) lncRNA in the metastatic potential of TSCC cells and its molecular mechanisms.
METHODS: Expression levels of MALAT-1 lncRNA were examined via quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in 127 TSCC samples as well as paired adjacent normal tissues and lymph node metastases (if exist). Lentiviral vectors expressing short hairpin RNA (shRNA) were used to knock down the expression of MALAT1 gene in two TSCC cell lines (CAL27 and SCC-25) with relatively higher MALAT-1 expression. Proliferational ability of the TSCC cells was analyzed using water soluble tetrazolium-1 (WST-1) assay. Metastatic abilities of TSCC cells were estimated in-vitro and in-vivo. We also performed a microarray-based screen to identify the genes influenced by MALAT-1 alteration, which were validated by real-time PCR analysis.
RESULTS: Expression of MALAT-1 lncRNA was enhanced in TSCCs, especially in those with lymph node metastasis (LNM). Knockdown (KD) of MALAT-1 lncRNA in TSCC cells led to impaired migration and proliferation ability in-vitro and fewer metastases in-vivo. DNA microarray analysis showed that several members of small proline rich proteins (SPRR) were up-regulated by KD of MALAT-1 lncRNA in TSCC cells. SPRR2A over-expression could impair distant metastasis of TSCC cells in-vivo.
CONCLUSION: Enhanced expression of MALAT-1 is associated with the growth and metastatic potential of TSCCs. Knock down of MALAT-1 in TSCCs leads to the up-regulation of certain SPRR proteins, which influenced the distant metastasis of TSCC cells.
PMID: 27586393 [PubMed - indexed for MEDLINE]
StatPearls
Book. 2017 06
Authors:
Abstract
The nasopharynx is a small, tubular structure above the soft palate that connects the nose to the oropharynx. Cancers that arise from this area are usually squamous cell carcinomas that behave differently than the other head and neck cancers. Most common place of origin is the fossa of Rosenmuller, which is the pharyngeal recess. Virus-related oncogenesis is a common theme in head/neck cancers. Oropharyngeal cancers are associated with human papillomavirus (HPV) infection, and nasopharyngeal cancers (NPC) are associated with Ebstein-Barr virus (EBV). The exact pathogenesis is still unknown. However viral oncogenes LMP-1, LMP-2, and EBNA1 have been known to play an important role. In areas with high incidence of disease, most cases are related to EBV infection. Although HPV related nasopharyngeal cancers have also been reported, no clear association has been established. The clinical behavior of nasopharyngeal cancers varies depending on its histological subtype. The World Health Organization (WHO) has classified nasopharyngeal carcinoma into the three subtypes based on histology. Type 1 is keratinizing squamous cell carcinoma which is associated with EBV infection in around 70% to 80% of the cases. Type 2 is differentiated non-keratinizing carcinoma, and type 3 is undifferentiated nonkeratinizing carcinoma and is the most common form of nasopharyngeal cancer. The latter two types are also most responsive to treatment. Almost all cases of type 2 and type 3 are related to EBV and occur in the area where EBV is endemic. Nasopharyngeal cancer with basaloid features is a newer, rarer histologic category, known to behave aggressively. Treatment does not vary based on histologic subtypes. In general, mortality related to nasopharyngeal cancers has improved in the last decade owing to early detection and advances in treatment.
PMID: 29083686
Related Articles |
Laryngeal surgical treatment in transgender women: A systematic review and meta-analysis.
Laryngoscope. 2017 Nov;127(11):2596-2603
Authors: Schwarz K, Fontanari AMV, Schneider MA, Borba Soll BM, da Silva DC, Spritzer PM, Kazumi Yamaguti Dorfman ME, Kuhl G, Costa AB, Cielo CA, Villas Bôas AP, Lobato MIR
Abstract
OBJECTIVE: To identify the effects of laryngeal surgical treatment in the voice of transgender women, especially on the fundamental frequency (f0).
STUDY DESIGN: We performed a systematic review in PubMed and Scopus in July 2016, covering the period between 2005 and 2016.
METHODS: Inclusion criteria were studies in English or Portuguese about the laryngeal surgical treatment in transgender women, featuring experimental design, title, year of publication, country of origin, journal of publication, participants, intervention, results. For the meta-analysis, only studies that had control group were selected. Exclusion criteria were articles that mentioned the use of surgical techniques but did not use the procedure in research, animal studies, studies of revision, and postmortem studies.
RESULTS: Four hundred and twenty-three articles were identified in the initial search; 94 were selected for analysis by two referees, independently. After applying all the selection criteria, five studies remained in the meta-analysis. The surgical procedures that were identified included laryngoplasty with or without thyrohyoid approximation, Wendler glottoplasty, cricothyroid approximation, laser glottoplasty reduction and the vocal fold shortening and retrodisplacement of anterior commissure. There was no significant difference between the experimental group and the control group in relation to f0.
CONCLUSION: No randomized clinical trials and prospective cohort studies are available, and a small number of retrospective cohort and case-control studies of surgical techniques reveal an increase in the f0. The evidence produced is not conclusive regarding which surgical technique would be better for vocal treatment of transgender women.
LEVEL OF EVIDENCE: NA Laryngoscope, 127:2596-2603, 2017.
PMID: 28671273 [PubMed - indexed for MEDLINE]
Home-based telehealth service for swallowing and nutrition management following head and neck cancer treatment.
J Telemed Telecare. 2017 Dec;23(10):866-872
Authors: Collins A, Burns CL, Ward EC, Comans T, Blake C, Kenny L, Greenup P, Best D
Abstract
Introduction Following (chemo)radiotherapy (C/RT) for head and neck cancer (HNC), patients return to hospital for regular outpatient reviews with speech pathology (SP) and nutrition and dietetics (ND) for acute symptom monitoring, nutritional management, and swallowing and communication rehabilitation. The aim of the current study was to determine the feasibility of a home-based telehealth model for delivering SP and ND reviews, to provide patients with more convenient access to these appointments. Methods Service outcomes, costs, and consumer satisfaction were examined across 30 matched participants: 15 supported via the standard model of care (SMOC), and 15 via the home-based telehealth model of care (TMOC). Results All patients were successfully managed via telehealth. The TMOC was more efficient, with a reduced number ( p < 0.003) and duration ( p < 0.01) of appointments required until discharge. Significant patient cost savings ( p = 0.002) were reported for the TMOC due to decreased travel requirements. While staff costs were reduced, additional telehealth equipment levies resulted in a lower but non-significant overall cost difference to the health service when using the TMOC. High satisfaction was reported by all participants attending the TMOC. Discussion The findings support the feasibility of a home-based telehealth model for conducting SP and ND reviews post C/RT for HNC.
PMID: 29081270 [PubMed - in process]
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Swallowing interventions for the treatment of dysphagia after head and neck cancer: a systematic review of behavioural strategies used to promote patient adherence to swallowing exercises.
BMC Cancer. 2017 Jan 10;17(1):43
Authors: Govender R, Smith CH, Taylor SA, Barratt H, Gardner B
Abstract
BACKGROUND: Dysphagia is a significant side-effect following treatment for head and neck cancers, yet poor adherence to swallowing exercises is frequently reported in intervention studies. Behaviour change techniques (BCTs) can be used to improve adherence, but no review to date has described the techniques or indicated which may be more associated with improved swallowing outcomes.
METHODS: A systematic review was conducted to identify behavioural strategies in swallowing interventions, and to explore any relationships between these strategies and intervention effects. Randomised and quasi-randomised studies of head and neck cancer patients were included. Behavioural interventions to improve swallowing were eligible provided a valid measure of swallowing function was reported. A validated and comprehensive list of 93 discrete BCTs was used to code interventions. Analysis was conducted via a structured synthesis approach.
RESULTS: Fifteen studies (8 randomised) were included, and 20 different BCTs were each identified in at least one intervention. The BCTs identified in almost all interventions were: instruction on how to perform the behavior, setting behavioural goals and action planning. The BCTs that occurred more frequently in effective interventions, were: practical social support, behavioural practice, self-monitoring of behaviour and credible source for example a skilled clinician delivering the intervention. The presence of identical BCTs in comparator groups may diminish effects.
CONCLUSIONS: Swallowing interventions feature multiple components that may potentially impact outcomes. This review maps the behavioural components of reported interventions and provides a method to consistently describe these components going forward. Future work may seek to test the most effective BCTs, to inform optimisation of swallowing interventions.
PMID: 28068939 [PubMed - indexed for MEDLINE]
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Coordination between respiration and swallowing during non-invasive positive pressure ventilation.
Respirology. 2016 Aug;21(6):1062-7
Authors: Hori R, Isaka M, Oonishi K, Yabe T, Oku Y
Abstract
BACKGROUND AND OBJECTIVE: The purpose of this study was to test the hypothesis that the risk of silent aspiration is increased in non-invasive positive pressure ventilation.
METHODS: We analysed the coordination between respiration and swallowing, in 12 young volunteers and 10 elder volunteers, by simultaneously monitoring respiratory flow, laryngeal movement and swallowing sound in three different conditions: control, continuous positive airway pressure (CPAP), and bi-level positive airway pressure (BiPAP). A step-wise multiple regression analysis was performed with the occurrence rate of inspiration after swallows as the dependent variable and various correlated variables as the independent variables.
RESULTS: In both subject groups, the occurrence rate of inspiration after swallow was greater with BiPAP compared with control and CPAP conditions. Repetitive saliva swallowing test count and swallow non-inspiratory flow occurrence rate were extracted as predictor variables for risk of inspiration after swallows during BiPAP treatment.
CONCLUSION: We found that the occurrence rate of inspiration after swallow is increased with BiPAP use irrespective of age. The results suggest that swallow non-inspiratory flow may trigger inspiratory support in the BiPAP mode, resulting in a risk of aspiration.
PMID: 27027264 [PubMed - indexed for MEDLINE]
Human Fetal Brain Connectome: Structural Network Development from Middle Fetal Stage to Birth.
Front Neurosci. 2017;11:561
Authors: Song L, Mishra V, Ouyang M, Peng Q, Slinger M, Liu S, Huang H
Abstract
Complicated molecular and cellular processes take place in a spatiotemporally heterogeneous and precisely regulated pattern in the human fetal brain, yielding not only dramatic morphological and microstructural changes, but also macroscale connectomic transitions. As the underlying substrate of the fetal brain structural network, both dynamic neuronal migration pathways and rapid developing fetal white matter (WM) fibers could fundamentally reshape early fetal brain connectome. Quantifying structural connectome development can not only shed light on the brain reconfiguration in this critical yet rarely studied developmental period, but also reveal alterations of the connectome under neuropathological conditions. However, transition of the structural connectome from the mid-fetal stage to birth is not yet known. The contribution of different types of neural fibers to the structural network in the mid-fetal brain is not known, either. In this study, diffusion tensor magnetic resonance imaging (DT-MRI or DTI) of 10 fetal brain specimens at the age of 20 postmenstrual weeks (PMW), 12 in vivo brains at 35 PMW, and 12 in vivo brains at term (40 PMW) were acquired. The structural connectome of each brain was established with evenly parcellated cortical regions as network nodes and traced fiber pathways based on DTI tractography as network edges. Two groups of fibers were categorized based on the fiber terminal locations in the cerebral wall in the 20 PMW fetal brains. We found that fetal brain networks become stronger and more efficient during 20-40 PMW. Furthermore, network strength and global efficiency increase more rapidly during 20-35 PMW than during 35-40 PMW. Visualization of the whole brain fiber distribution by the lengths suggested that the network reconfiguration in this developmental period could be associated with a significant increase of major long association WM fibers. In addition, non-WM neural fibers could be a major contributor to the structural network configuration at 20 PMW and small-world network organization could exist as early as 20 PMW. These findings offer a preliminary record of the fetal brain structural connectome maturation from the middle fetal stage to birth and reveal the critical role of non-WM neural fibers in structural network configuration in the middle fetal stage.
PMID: 29081731 [PubMed]
Supplemental Screening Breast US in Women with Negative Mammographic Findings: Effect of Routine Axillary Scanning.
Radiology. 2017 Oct 30;:171218
Authors: Lee SH, Yi A, Jang MJ, Chang JM, Cho N, Moon WK
Abstract
Purpose To evaluate the effect of routine axillary scanning when supplemental screening breast ultrasonography (US) is performed in women with negative mammographic findings. Materials and Methods This retrospective review included 12 844 screening breast US examinations performed in 8664 asymptomatic women aged 40 years or older with dense breasts and negative results for cancer at mammography performed between January 2012 and December 2014. Bilateral whole-breast US was performed with a handheld device by one of 10 experienced radiologists. The bilateral axillae were routinely scanned, and representative images were documented in all examinations. The abnormal interpretation rate (AIR), cancer detection rate (CDR), and positive predictive value (PPV) of screening breast US with and without axillary scanning were calculated. The 95% confidence intervals (CIs) were calculated for cancer detection after an abnormal finding at screening US. Results The frequency of positive axillary findings was 3.5 per 1000 (14 of 4009) baseline screening US examinations and 2.2 per 1000 (19 of 8835) subsequent screening US examinations. Of the 33 women with 33 positive axillary findings, 11 had positive breast findings; none were diagnosed with breast cancer. The remaining 22 women showed positive findings only in the axilla. The axillary findings revealed no malignancy at biopsy (n = 12) or during 22-54-month follow-up (n = 21) (95% CI: 0%, 10.6%). Without routine axillary scanning, the AIR of screening US decreased from 15.2% (610 of 4009 examinations) to 15.0% (602 of 4009 examinations) at baseline US and from 8.1% (714 of 8835 examinations) to 7.9% (700 of 8835 examinations) at subsequent US examinations, and the PPV for biopsy performed increased from 6.0% (five of 83 examinations) to 6.4% (five of 78 examinations) at baseline US and from 7.6% (13 of 170 examinations) to 7.9% (13 of 164 examinations) at subsequent US examinations, without a change in the CDR. Conclusion Routine axillary scanning during screening breast US had no effect on additional cancer detection, but rather increased the number of false-positive results. However, the conclusions based on these findings must be tempered by the low rate of positive findings. (©) RSNA, 2017.
PMID: 29083988 [PubMed - as supplied by publisher]
Amide Proton Transfer MR Imaging of Endometrioid Endometrial Adenocarcinoma: Association with Histologic Grade.
Radiology. 2017 Oct 30;:170349
Authors: Takayama Y, Nishie A, Togao O, Asayama Y, Ishigami K, Ushijima Y, Okamoto D, Fujita N, Sonoda K, Hida T, Ohishi Y, Keupp J, Honda H
Abstract
Purpose To evaluate the utility of amide proton transfer (APT) imaging in estimating histologic grades of endometrioid endometrial adenocarcinoma (EEA). Materials and Methods The institutional review board approved this prospective study. Between June 2012 and March 2016, 32 patients with EEA underwent magnetic resonance (MR) imaging. After their surgical procedures, their EEAs were confirmed pathologically and classified into histologic grades: grade 1 (n = 11), grade 2 (n = 11), and grade 3 (n = 10). The APT signal intensities (SIs) and the mean and minimum apparent diffusion coefficients (ADCs) of the three grades were calculated and compared. Spearman rank correlation coefficient was also calculated between the APT SIs and histologic grades, and between the ADCs and histologic grades. Results The Spearman correlation coefficient with histologic grade of the APT SIs, the mean ADC, and the minimum ADC were 0.55 (P = .001), 0.03 (P = .84), and -0.30 (P = .09), respectively. The average APT SIs and the mean and minimum ADCs were 2.2% ± 0.2 (standard deviation), 0.9 × 10(-3) mm(2)/sec ± 0.2, and 0.6 × 10(-3) mm(2)/sec ± 0.1 for grade 1; 3.2% ± 0.3, 0.8 × 10(-3) mm(2)/sec ± 0.1, and 0.5 × 10(-3) mm(2)/sec ± 0.1 for grade 2; and 3.7% ± 0.3, 0.9 × 10(-3) mm(2)/sec ± 0.1, and 0.5 × 10(-3) mm(2)/sec ± 0.1 for grade 3, respectively. The APT SIs of grade 3 EEA were significantly higher than those of grade 1 EEA (P = .01), but other pairwise comparisons did not reveal any significant differences (P = .06-.51). The mean and minimum ADCs showed no significant differences among the three histologic grades (P =.13-.51). Conclusion The APT SI was positively correlated with the histologic grades of EEA. (©) RSNA, 2017 Online supplemental material is available for this article.
PMID: 29083987 [PubMed - as supplied by publisher]
Effect of General Anesthesia versus Conscious Sedation for Stroke Thrombectomy on Angiographic Workflow in a Randomized Trial: A Post Hoc Analysis of the SIESTA Trial.
Radiology. 2017 Oct 30;:171002
Authors: Pfaff JAR, Schönenberger S, Nagel S, Ringleb PA, Hacke W, Bendszus M, Bösel J, Möhlenbruch MA
Abstract
Purpose To investigate whether the sedation mode (ie, conscious sedation [CS] vs general anesthesia [GA]) affects the angiographic workflow applied for treatment of endovascular stroke in a post hoc analysis of a recent randomized controlled trial, Sedation versus Intubation for Endovascular Stroke Treatment (SIESTA). Materials and Methods SIESTA was an institutional review board-approved, single-center, prospective, randomized, parallel-group, open-label treatment trial with a blinded end-point evaluation to compare GA with CS for treatment of endovascular stroke in 73 and 77 patients, respectively. By using descriptive data from SIESTA, the influence of the mode of sedation on angiographic workflow during treatment for endovascular stroke (eg, procedure times) and other radiologic outcome parameters (eg, radiation exposure) were analyzed. The time between angiographic key steps for patients who underwent GA and CS was evaluated with t tests. P values were corrected for false discovery rate. Results The median time from groin puncture to first intracranial flow restoration with CS was 47 minutes (interquartile range [IQR], 29-70 minutes), and for GA, it was 41 minutes (IQR, 28-60 minutes) (P = .546). The median time to the end of angiography with CS was 104 minutes (IQR, 75-150 minutes), and with GA, it was 73 minutes (IQR, 53-125 minutes) (P = .052). Fluoroscopy time with CS was 49 minutes (IQR, 25-85 minutes), and with GA, it was 35 minutes (IQR, 20-74 minutes) (P = .098). The times were comparable in both groups for these measures. The time from groin puncture to the final angiographic result with GA, at 72 minutes (IQR, 45-109 minutes) was shorter than that with CS, at 98 minutes (IQR, 64-135 minutes) (P = .048). Conclusion This post hoc analysis of the single-center SIESTA trial revealed that time from groin puncture to final angiographic result was shorter with patients under GA than that with patients under CS. (©) RSNA, 2017 Online supplemental material is available for this article.
PMID: 29083986 [PubMed - as supplied by publisher]
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Inner ear manifestations in CHARGE: Abnormalities, treatments, animal models, and progress toward treatments in auditory and vestibular structures.
Am J Med Genet C Semin Med Genet. 2017 Oct 30;:
Authors: Choo DI, Tawfik KO, Martin DM, Raphael Y
Abstract
The inner ear contains the sensory organs for hearing and balance. Both hearing and balance are commonly affected in individuals with CHARGE syndrome (CS), an autosomal dominant condition caused by heterozygous pathogenic variants in the CHD7 gene. Semicircular canal dysplasia or aplasia is the single most prevalent feature in individuals with CHARGE leading to deficient gross motor skills and ambulation. Identification of CHD7 as the major gene affected in CHARGE has enabled acceleration of research in this field. Great progress has been made in understanding the role of CHD7 in the development and function of the inner ear, as well as in related organs such as the middle ear and auditory and vestibular neural pathways. The goals of current research on CHD7 and CS are to (a) improve our understanding of the pathology caused by CHD7 pathogenic variants and (b) to provide better tools for prognosis and treatment. Current studies utilize cells and whole animals, from flies to mammals. The mouse is an excellent model for exploring mechanisms of Chd7 function in the ear, given the evolutionary conservation of ear structure, function, Chd7 expression, and similarity of mutant phenotypes between mice and humans. Newly recognized developmental functions for mouse Chd7 are shedding light on how abnormalities in CHD7 might lead to CS symptoms in humans. Here we review known human inner ear phenotypes associated with CHD7 pathogenic variants and CS, summarize progress toward diagnosis and treatment of inner ear-related pathologies, and explore new avenues for treatment based on basic science discoveries.
PMID: 29082607 [PubMed - as supplied by publisher]
Systematic analysis reveals a lncRNA-mRNA co-expression network associated with platinum resistance in high-grade serous ovarian cancer.
Invest New Drugs. 2017 Oct 30;:
Authors: Fang L, Wang H, Li P
Abstract
Resistance to platinum-based chemotherapy is the major barrier to treating high-grade serous ovarian cancer (HGS-OvCa). To improve HGS-OvCa patient prognosis, it is critical to identify the underlying mechanisms that promote platinum resistance. The goal of the present study was to identify a lncRNA-mRNA co-expression network and key lncRNAs that predict resistance to platinum-based chemotherapy in ovarian cancer patients. By systematically analyzing the expression profiles of lncRNAs and mRNAs in HGS-OvCa samples from the Cancer Genome Atlas (TCGA), we revealed that lncRNAs play important roles in platinum resistance in HGS-OvCa patients and delineate a lncRNA-mRNA co-expression network in HGS-OvCa patients who exhibit platinum resistance. Within the platinum resistance-specific lncRNA-mRNA network, 35 lncRNAs and 270 mRNAs showed 124 significant lncRNA-mRNA co-expression relationships. Pathway analysis revealed that lncRNAs in the platinum resistance network may participate in platinum resistance by regulating metabolic pathways. Moreover, HGS-OvCa patients with low lncRNA RP5-1120P11.1 expression showed a poorer prognosis than those with high lncRNA RP5-1120P11.1 expression in TCGA dataset (P = 2.74 × 10(-5), log rank test), which was also validated in the GSE63885 dataset (P = 0.0242, log rank test). Network and function analysis revealed that lncRNA RP5-1120P11.1 regulates many cancer-related signaling pathways, such as the PI3K-AKT signaling pathway (P = 1.02 × 10(-5), hypergeometric test) and the Jak-STAT signaling pathway (P = 1.71 × 10(-4), hypergeometric test). Particularly, lncRNA RP5-1120P11.1 expression is significantly positively correlated with ABCC10 gene expression (P = 3.89 × 10(-3), Pearson correlation test). Both lncRNA RP5-1120P11.1 and ABCC10 were down-regulated in platinum-resistant HGS-OvCa patients, and RP5-1120P11.1 is located near ABCC10 on chromosome 6. Gene ABCC10 has been implicated in resistance to docetaxel treatment. The present study paves the way for investigating lncRNA functions in platinum drug resistance and identifying lncRNAs with prognostic and therapeutic potential in HGS-OvCa.
PMID: 29082457 [PubMed - as supplied by publisher]
Facile synthesis of highly biocompatible folic acid-functionalised SiO2 nanoparticles encapsulating rare-earth metal complexes, and their application in targeted drug delivery.
Dalton Trans. 2017 Oct 30;:
Authors: Xu X, Hu F, Shuai Q
Abstract
Mesoporous silica core-shell nanospheres encapsulating a rare-earth metal complex (RC) were first synthesised through a facile W/O (water in oil) inverse microemulsion method. In order to achieve targeted complex delivery, folic acid (FA) was used as the targeting component due to its high affinity for over-expressed folate receptors (FRs) in cancer cells. The RC2@SiO2-FA nanospheres were characterised via ultraviolet-visible light absorption spectroscopy (UV-vis spectroscopy), dynamic light scattering (DLS), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). A microwave method was used to synthesise five RC cores based on 4-chlorophenoxyacetic acid, and their crystal structures were further confirmed using X-ray diffraction. The five RC cores have the following chemical formulae: [Er2(p-CPA)6(H2O)6] RC1, [Ho2(p-CPA)6(H2O)6] RC2, [Sm(p-CPA)3(H2O)] RC3, [Pr(p-CPA)3(H2O)]·3H2O RC4 and [Ce(p-CPA)3(H2O)2]·2H2O RC5. The carboxyl groups showed two kinds of coordination modes, namely μ2-η(1):η(1) and μ2-η(1):η(2), among RC1-RC5. The flexible -OCH2COO- spacer group, which can undergo rotation of its C-O and C-C bonds, offered great potential for structural diversity. In vivo experiments revealed that the nanospheres exhibited no obvious cytotoxicity on HepG2 cells and 293 T cells, even at concentrations of up to 80 μg mL(-1). Nevertheless, all of the RC cores showed a certain degree of anti-tumour efficacy; in particular, RC2 showed the strongest cytotoxicity against HepG2 cells. Interestingly, the cytotoxicity of all of the RC2@SiO2-FA nanospheres was higher than that of lone RC2. These types of FA-targeted mesoporous silica nanocarriers can be used for the delivery of anti-tumour RC, and provide a basis for the further study of affordable non-platinum-based complexes.
PMID: 29082408 [PubMed - as supplied by publisher]
Clinical staging of NSCLC: current evidence and implications for adjuvant chemotherapy.
Ther Adv Med Oncol. 2017 Sep;9(9):599-609
Authors: Heineman DJ, Daniels JM, Schreurs WH
Abstract
Survival of all non-small cell lung cancer (NSCLC) patients is disappointing, with a 5-year survival of 18%. Staging NSCLC patients is crucial because it determines the choice of treatment and prognosis. Clinical staging is a complex process that comes with many challenges and with low accuracy between the clinical and pathological stage. Treatment modalities for stage I-III NSCLC consist of surgical resection, radiotherapy and chemotherapy. This review describes the current evidence on staging and the implications on adjuvant chemotherapy. For stage I disease, staging is most accurate. Primary treatment consists of surgery or stereotactic ablative radiotherapy. When a patient has stage II disease, staging is less accurate because more diagnostic modalities are necessary to stage the mediastinal lymph nodes. Surgery remains the primary treatment modality and platinum-based adjuvant chemotherapy gives a 4% 5-year survival benefit. Staging patients with stage III disease is difficult because of the heterogeneity of the patients. It should be decided if a patient has potentially resectable disease with or without risk of incomplete resection. Induction therapy with chemo(radio)therapy followed by surgical resection or definitive chemoradiotherapy are the treatments of choice. The 5-year survival can reach 44% in selected patients. Decisions in staging and treating patients with NSCLC should be made by a multidisciplinary team with sufficient expertise in all aspects of staging and treatment.
PMID: 29081843 [PubMed]
Niraparib in ovarian cancer: results to date and clinical potential.
Ther Adv Med Oncol. 2017 Sep;9(9):579-588
Authors: Caruso D, Papa A, Tomao S, Vici P, Panici PB, Tomao F
Abstract
Ovarian cancer is the first cause of death from gynaecological malignancy. Germline mutation in BRCA1 and 2, two genes involved in the mechanisms of reparation of DNA damage, are showed to be related with the incidence of breast and ovarian cancer, both sporadic and familiar. PARP is a family of enzymes involved in the base excision repair (BER) system. The introduction of inhibitors of PARP in patients with BRCA-mutated ovarian cancer is correlated with the concept of synthetic lethality. Among the PARP inhibitors introduced in clinical practice, niraparib showed interesting results in a phase III trial in the setting of maintenance treatment in ovarian cancer, after platinum-based chemotherapy. Interestingly, was niraparib showed to be efficacious not only in BRCA-mutated patients, but also in patients with other alterations of the homologous recombination (HR) system and in patients with unknown alterations. These results position niraparib as the first PARP-inhibitor with clinically and statistically significant results also in patients with no alterations in BRCA 1/2 and other genes involved in the DNA repair system. Even if the results are potentially practice-changing, the action of niraparib must be further studied and deepened.
PMID: 29081841 [PubMed]
Secondary Laparoscopic Cytoreduction in Recurrent Ovarian Cancer: a Large, Single Institution Experience.
J Minim Invasive Gynecol. 2017 Oct 25;:
Authors: Valerio G, Conte C, Teresa GM, Camilla N, Giuseppe V, Salvatore GA, Stefano C, Claudio L, Andrea DG, Maria RA, Anna F, Giovanni S, Gabriella F
Abstract
STUDY OBJECTIVE: To analyze the feasibility and safety of laparoscopic secondary cytoreductive surgery in a retrospective series of platinum sensitive recurrent ovarian cancer patients.
DESIGN: Retrospective cohort study (Canadian Task Force classification II-2).
SETTING: Catholic University of the Sacred Hearth, Rome, Italy.
PATIENTS: Between October 2010 and October 2016, 58 patients with recurrent ovarian cancer were selected for a retrospective analysis of data.
INTERVENTIONS: All patients underwent a laparoscopic secondary cytoreduction with single or multiple procedures.
RESULTS: The most frequent pattern of recurrence was represented by the peritoneal one (48.3%); there were 6 patients (10.3%) experiencing parenchymal disease (spleen=5, liver=1), and 24 patients (41.4%) presenting lymph node recurrence. Complete debulking was achieved for 100% of the patients. The median operative time was 204 minutes (range 55-448), estimated blood loss was70 mL (range 20-300), and the median length of hospital stay was 4 days (range 1-21). There were 4 (6.8%) intra-operative complications. Early post-operative complications were documented in 6 patients (10.3%), but only one G3 complication. The median follow-up since secondary cytoreduction was 24 months (range: 9-71). There were 21 cases (36.2%) experiencing second relapse of disease; the median progression free survival (PFS) was 28 months (2-yr PFS: 58.7%). We documented 5 cases experiencing death of disease (8.6%) patients; the 2-yr OS rate was 90.7%.
CONCLUSIONS: For selected patients, laparoscopy is a feasible and safe approach to optimal cytoreduction for patients with recurrent ovarian cancer.
PMID: 29081384 [PubMed - as supplied by publisher]
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Combined treatment with pemetrexed and vinflunine in patients with metastatic urothelial cell carcinoma after prior platinum-containing chemotherapy - results of an exploratory phase I study.
Invest New Drugs. 2017 Oct 28;:
Authors: Pappot H, von der Maase H, Ullén A, Agerbæk M, NUCOG - Nordic Urothelial Cancer Oncology Group (NUCOG)
Abstract
Vinflunine is to date the only registered agent for second-line treatment of metastatic urothelial cell carcinoma (UCC) in Europe. However, the effect is modest. Pemetrexed has demonstrated some single-agent activity in this disease entity. In order to improve treatment possibilities for UCC patients, a phase I trial (VINTREX) was undertaken to assess the safety of vinflunine and pemetrexed in metastatic UCC patients. A dose escalation design was planned to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of a vinflunine/pemetrexed combination. Pemetrexed was added to vinflunine dosed at 280 mg/m2 on day 1 of a 21-day cycle. Three levels of pemetrexed were planned starting at 400 mg/m2. Four patients were enrolled with a mean age of 66 years and with a mean number of prior GC-cycles of 6,8. Two DLT's were observed at the lowest dose-level in cohort 1. One patient experienced grade 4 thrombocytopenia and a second demonstrated hepatobiliary toxicity grade 3 with an increase in alanine aminotransaminase. Most common grade 3 and 4 adverse events were anemia, thrombocytopenia and neutropenia. Three out of four patients received 3 cycles of pemetrexed and vinflunine, all had progressive disease. Based on these observations and due to protocol design, the study was interrupted at dose level 1 for safety reasons. The combined therapy of vinflunine (Javlor®, Pierre Fabre Pharma) and pemetrexed (Alimta®, Eli Lilly) is poorly tolerated in metastatic UCC patients. The combination cannot be recommended for further investigations in metastatic UCC.
PMID: 29081023 [PubMed - as supplied by publisher]
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Combination chemotherapy with irinotecan and gemcitabine for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancer: a multicenter phase I/II trial (GOGO-Ov 6).
Cancer Chemother Pharmacol. 2017 Oct 28;:
Authors: Yoshino K, Kamiura S, Yokoi T, Nakae R, Fujita M, Takemura M, Adachi K, Wakimoto A, Nishizaki T, Shiki Y, Tsutsui T, Kanda Y, Kobayashi E, Hashimoto K, Mabuchi S, Ueda Y, Sawada K, Tomimatsu T, Kimura T
Abstract
PURPOSE: To develop a new therapeutic strategy for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancers, we evaluated the feasibility and efficacy of irinotecan and gemcitabine combination chemotherapy.
METHODS: Patients with taxane/platinum-resistant/refractory cancer received escalating doses of irinotecan and gemcitabine (level 1: 80 and 800 mg/m(2), respectively; level 2: 100 and 1000 mg/m(2)) on days 1 and 8 on a 21-day cycle. Genotyping for UGT1A1*6 and *28 polymorphisms was performed for possible adverse irinotecan sensitivity.
RESULTS: A total of 35 patients were enrolled. The recommended dose was defined as 100 mg/m(2) irinotecan and 1000 mg/m(2) gemcitabine (level 2). The observed common grade 3/4 toxicities were neutropenia (60%), anemia (17.1%), diarrhea (8.6%), thrombocytopenia (5.7%) and nausea (5.7%). Groups homozygous for UGT1A1*6 or *28 were associated with grade 3/4 neutropenia and diarrhea. Objective responses were 20%, including one complete response and six partial responses. In 29 patients treated with the recommended dose, the median progression-free survival and overall survival were 3.8 months (95% CI 2.1-6.0 months) and 17.4 months (95% CI 9.9-21.9 months), respectively, while the 1-year survival rate was 58.6%.
CONCLUSIONS: Combination chemotherapy with irinotecan and gemcitabine represents a safe and effective treatment combination for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancers.
PMID: 29080971 [PubMed - as supplied by publisher]
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Preventing chemotherapy-induced nausea and vomiting in patients with lung cancer: efficacy of NEPA (netupitant-palonosetron), the first combination antiemetic.
Support Care Cancer. 2017 Oct 28;:
Authors: Hesketh PJ, Palmas M, Nicolas P
Abstract
PURPOSE: Patients receiving platinum-based chemotherapy are at high risk of chemotherapy-induced nausea and vomiting (CINV), a distressing side effect of treatment. This post-hoc subgroup analysis of two pivotal trials evaluated the efficacy of NEPA in preventing CINV in subsets of patients with lung cancer who received cisplatin or carboplatin.
METHODS: In each study, the efficacy endpoints complete response (CR; defined as no emetic episodes and no rescue medication) and no significant nausea (NSN; defined as a score of < 25 mm on a visual analog scale of 0-100 mm) during the acute (0-24 h), delayed (25-120 h), and overall (0-120 h) phases post-chemotherapy in cycle 1 (study 1) and cycles 1-4 (study 2) were assessed. Safety was evaluated by recording treatment-emergent adverse events (AEs) and treatment-related AEs.
RESULTS: NEPA treatment resulted in high CR rates across the acute, delayed, and overall phases (cisplatin: > 88% overall CR; carboplatin: > 75% overall CR), with higher CR rates for NEPA-treated patients than those receiving palonosetron; moreover, CR rates were sustained over multiple chemotherapy cycles (> 75%). High rates of NSN observed during cycle 1 (> 79%) were also maintained over multiple chemotherapy cycles. NEPA was well tolerated in all patients.
CONCLUSIONS: NEPA appears to be effective and well tolerated in patients with lung cancer receiving platinum-based chemotherapy, across the acute, delayed, and overall phases and throughout multiple cycles. As a highly effective oral combination antiemetic agent administered as a single dose once per cycle, NEPA may offer a convenient, simplified prophylactic antiemetic.
PMID: 29080920 [PubMed - as supplied by publisher]
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Supramolecular Delivery Systems for Non-Platinum Metal-Based Anticancer Drugs.
Crit Rev Ther Drug Carrier Syst. 2017;34(2):149-183
Authors: Ringhieri P, Morelli G, Accardo A
Abstract
Stimulated by the enormous success of the inorganic complex cisplatin in tumor treatment, interest in metal complexes has recently grown. Within cells, metal complexes can participate in reactions that are not possible with conventional organic substances, and most of them have promising efficacy as anticancer drugs. However, to be effective in vivo metal complexes need adequate delivery systems able to increase their water solubility, the in vivo bioavailability, and the safe delivery to target organs. The present review reports on the state of the art of these new, nonplatinum, anticancer metallodrugs delivered by nanosized vehicles. The development of complexes of ruthenium, gold, cobalt, copper, gallium, and others that show promising antitumor efficacy is reported, and we emphasize the different approaches in the individuation of the most appropriate delivery system for each of them.
PMID: 28605318 [PubMed - indexed for MEDLINE]
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Safety and efficacy of lobaplatin combined with 5-fluorouracil as first-line induction chemotherapy followed by lobaplatin-radiotherapy in locally advanced nasopharyngeal carcinoma: preliminary results of a prospective phase II trial.
BMC Cancer. 2017 Feb 15;17(1):134
Authors: Ke LR, Xia WX, Qiu WZ, Huang XJ, Yang J, Yu YH, Liang H, Liu GY, Ye YF, Xiang YQ, Guo X, Lv X
Abstract
BACKGROUND: Due to improvements in imaging and radiological techniques as well as the use of chemotherapy, distant metastasis has become the predominant mode of treatment failure in patients with locally advanced nasopharyngeal carcinoma (LA-NPC). Platinum-based systemic chemotherapy has shown survival benefits and is now the standard strategy for systemic therapy in patients with LA-NPC. Notably, the third-generation platinum reagent lobaplatin has shown anti-tumor effects in several solid tumors with lower incidences of gastrointestinal, hepatic and renal toxicity relative to other platinum drugs. However, the safety and efficacy of lobaplatin as a first-line regimen in patients with LA-NPC are undetermined.
METHODS: Patients with stage III-IVa-b NPC received lobaplatin at a dose of 30 mg/m2 on days 1 and 22 combined with a continuous 120-h intravenous injection of 5-fluorouracil at a dose of 4 g/m2 followed by lobaplatin at a dose of 50 mg/m2 on days 43 and 64 concomitant with intensity-modulated radiation therapy. Objective response rates and acute toxicity were assessed based on RECIST (1.1) and CTCAE v.3.0, respectively. Kaplan-Meier analysis was used to calculate survival rates.
RESULTS: Fifty-nine patients were enrolled, and 44 patients (74.6%) received allocated cycles of chemotherapy. The objective response rates were 88.1% (95% confidence interval [CI], 0.77 to 0.95) and 100% after induction chemotherapy (ICT) and concurrent chemoradiotherapy (CRT), respectively. With a median follow-up period of 44 months, the 3-year estimated progression-free survival and overall survival were 86.4% (95% CI, 69.8 to 98.8) and 94.9% (95% CI, 89.5 to 100), respectively. The most common grade 3-4 toxicities were neutropenia (8.5%) and thrombocytopenia (40.7%) after ICT and CRT, respectively.
CONCLUSION: Lobaplatin combined with 5-fluorouracil followed by lobaplatin-RT treatment showed encouraging anti-tumor effects with tolerable toxicities in patients with LA-NPC. Randomized controlled trials of lobaplatin in patients with LA-NPC are warranted.
TRIAL REGISTRATION: This trial was registered with the Chinese Clinical Trials Registry and approved on March 31(st), 2012, number ChiCTR-ONC-12002060 .
PMID: 28202000 [PubMed - indexed for MEDLINE]
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Programmed cell death-ligand 1 (PD-L1) expression and fibroblast growth factor receptor 1 (FGFR1) amplification in stage III/IV lung squamous cell carcinoma (SQC).
Thorac Cancer. 2017 Mar;8(2):73-79
Authors: Guo Q, Sun Y, Yu S, Bai H, Zhao J, Zhuo M, Wang J
Abstract
BACKGROUND: This study was conducted to explore programmed cell death-ligand-1 (PD-L1) expression and fibroblast growth factor receptor 1 (FGFR1) amplification in stage IIIB/IV lung squamous cell carcinoma (SQC). Correlations between PD-L1 and FGFR1, and with clinicopathological characteristics, efficacy of platinum-based chemotherapy, and prognosis were analyzed.
METHODS: One hundred and twenty-eight consecutive stage III/IV SQC patients were enrolled in this study from 2009 to 2014. Seventy-eight patients received platinum-based chemotherapy. Immunohistochemistry was used to assess PD-L1 expression and fluorescence in situ hybridization was applied to detect FGFR1 amplification.
RESULTS: PD-L1 expression was detected in 61.7% (79/128) of lung SQC patients. Smokers had significantly higher PD-L1 expression rates than non-smokers (66.1% vs. 44.0%, P = 0.042, respectively). The objective response and disease control rates for platinum-based chemotherapy were not significantly different between PD-L1 negative and positive patients (43.3% vs. 36.2%, P = 0.434; 80.0% vs. 78.7% P = 0.840, respectively); however, overall survival in PD-L1-negative patients was significantly longer than in PD-L1-positive patients (41.5 vs. 19.3 months, P = 0.001). Twenty-five percent (32/128) of patients displayed FGFR1 amplification, with a lower rate in stage III patients compared to stage IV (17.1% vs. 36.5%, P = 0.013, respectively). There was no significant difference in FGFR1 amplification levels between overall response, disease control or overall survival rates. No correlation was observed between PD-L1 expression and FGFR1 amplification ( P = 0.916).
CONCLUSION: PD-L1 expression may function as a prognostic factor in Chinese stage III/IV SQC patients. FGFR1 amplification is more prevalent in late stage SQC patients but does not predict chemotherapy response. There is no apparent correlation between PD-L1 expression and FGFR1 amplification.
PMID: 28008744 [PubMed - indexed for MEDLINE]
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Supramolecular PEGylated Dendritic Systems as pH/Redox Dual-Responsive Theranostic Nanoplatforms for Platinum Drug Delivery and NIR Imaging.
Theranostics. 2016;6(9):1293-305
Authors: Li Y, Li Y, Zhang X, Xu X, Zhang Z, Hu C, He Y, Gu Z
Abstract
Recently, self-assembling small dendrimers into supramolecular dendritic systems offers an alternative strategy to develop multifunctional nanoplatforms for biomedical applications. We herein report a dual-responsive supramolecular PEGylated dendritic system for efficient platinum-based drug delivery and near-infrared (NIR) tracking. With a refined molecular/supramolecular engineering, supramolecular dendritic systems were stabilized by bioreducible disulfide bonds and endowed with NIR fluorescence probes, and PEGylated platinum derivatives coordinated onto the abundant peripheral groups of supramolecular dendritic templates to generate pH/redox dual-responsive theranostic supramolecular PEGylated dendritic systems (TSPDSs). TSPDSs markedly improved the pharmacokinetics and biodistribution of platinum-based drugs, owing to their stable nanostructures and PEGylated shells during the blood circulation. Tumor intracellular environment (low pH value and high glutathione concentration) could trigger the rapid disintegration of TSPDSs due to acid-labile coordination bonds and redox-cleavable disulfide linkages, and then platinum-based drugs were delivered into the nuclei to exert antitumor activity. In vivo antitumor treatments indicated TSPDSs not only provided high antitumor efficiency which was comparable to clinical cisplatin, but also reduced renal toxicity of platinum-based drugs. Moreover, NIR fluorescence of TSPDSs successfully visualized in vitro and in vivo fate of nanoplatforms and disclosed the intracellular platinum delivery and pharmacokinetics. These results confirm tailor-made supramolecular dendritic system with sophisticated nanostructure and excellent performance is a promising candidate as smart theranostic nanoplatforms.
PMID: 27375780 [PubMed - indexed for MEDLINE]
StatPearls
Book. 2017 06
Authors:
Abstract
Doxorubicin (Adriamycin) is an antibiotic derived from the Streptomyces peucetius bacterium. It has been widely used as a chemotherapeutic agent since the 1960s. Doxorubicin is part of the anthracycline group of chemotherapeutic agents; other anthracyclines include daunorubicin, idarubicin, and epirubicin. Commonly, doxorubicin is used in the treatment of solid tumors in adult and pediatric patients. Doxorubicin may be used to treat soft tissue and bone sarcomas as well as cancers of the breast, ovary, bladder, and thyroid. It is also used in the treatment of acute lymphoblastic leukemia, acute myeloblastic leukemia, Hodgkin lymphoma, and small cell lung cancer. The liposomal formulation of doxorubicin, Doxil, is FDA-approved for the treatment of ovarian cancer in patients who have failed platinum-based chemotherapy, AIDS-related Kaposi sarcoma, and multiple myeloma.
PMID: 29083582
Frailty: the missing piece of the pre- hematopoietic cell transplantation assessment?
Bone Marrow Transplant. 2017 Oct 30;:
Authors: Hegde A, Murthy HS
Abstract
Hematopoietic stem cell transplantation (HSCT) represents a curative option for those afflicted with numerous hematologic malignancies and bone marrow failure syndromes. Advances and refinement of the HSCT process have resulted in increasing number of transplants performed on older patients in the recent years. Pre-transplant assessments (PTA) function to risk stratify patients prior to undergoing HSCT in an effort to predict those at higher risk of treatment-related toxicity, to inform risk/benefit assessments and to aid clinical decision making. Traditionally used risk stratification parameters such as chronologic age, comorbidity and performance status may not fully capture physical function, physiologic fitness, highlighting a need for improvement in PTA. Incorporation of frailty measurements in pre-HSCT assessments, particularly in elderly transplant candidates, may result in improving predictive ability of existing tools such as the Hematopoietic Cell Transplantation Comorbidity Index and Karnofsky performance status. Here, we review existing pre-HSCT assessment tools, measures of frailty that may aid in risk stratification for patients undergoing HSCT and directions for future research using frailty in the pre-HSCT setting.Bone Marrow Transplantation advance online publication, 30 October 2017; doi:10.1038/bmt.2017.192.
PMID: 29084201 [PubMed - as supplied by publisher]
Ethnobotanic, Ethnopharmacologic Aspects and New Phytochemical Insights into Moroccan Argan Fruits.
Int J Mol Sci. 2017 Oct 30;18(11):
Authors: Khallouki F, Eddouks M, Mourad A, Breuer A, Owen RW
Abstract
This review summarizes available data on argan fruit botany, geographical distribution, traditional uses, environmental interest, socioeconomic role, phytochemistry, as well as health beneficial effects and examination of future prospects. In particular, ethnomedical uses of argan fruits are carried out throughout Morocco where it has been used against various diseases. Different classes of bioactive compounds have been characterized including essential oils, fatty acids, triacylglycerols, flavonoids and their newly reported acylglycosyl derivatives, monophenols, phenolic acids, cinnamic acids, saponins, triterpenes, phytosterols, ubiquinone, melatonin, new aminophenols along with vitamin E among other secondary metabolites. The latter have already shown a wide spectrum of in vitro, and ex vivo biologicalactivities including antioxidant, anti-inflammatory, anti-diabetic, antihypertensive, anti-hypercholesterolemia, analgesic, antimicrobial, molluscicidal anti-nociceptive and anticancer potential. Argan flesh (pulp) contains a broad spectrum of polyphenolic compounds which may have utility for incorporation into nutraceuticals and cosmeceuticals relevant to the food, cosmetic and health industries. Further research is recommended, especially on the health beneficial effects of the aminophenols.
PMID: 29084170 [PubMed - in process]
Determinants of physical, affective, and cognitive fatigue: During breast cancer therapy and 12 months follow-up.
Int J Cancer. 2017 Oct 30;:
Authors: Schmidt ME, Wiskemann J, Schneeweiss A, Potthoff K, Ulrich CM, Steindorf K
Abstract
Fatigue is common in cancer survivors but often insufficiently treated. Due to its complexity a one-size-fits-all treatment seems not appropriate. To gain more information on influencing factors and sub-dimensions of fatigue we investigated potential determinants and correlates of physical, affective, and cognitive fatigue in breast cancer survivors during and after adjuvant therapy. Within the follow-up of two randomized controlled trials physical, affective, and cognitive fatigue were repeatedly assessed during and up to 12 months after cancer therapy with the 20-item Fatigue Assessment Questionnaire in 255 breast cancer survivors. Determinants of the different fatigue dimensions over time were explored with linear mixed models. Chemotherapy appeared as significant precipitating factor for physical fatigue. However, type of cancer therapy had no impact on fatigue one year post-treatment. Obesity was significantly associated with increased physical fatigue throughout all time points (Δ=15.5 at 12 months) whereas exercise appeared to be beneficial (Δ=-6.3). In contrast, affective fatigue was significantly associated with poor social support and worries about the future. In addition, poor sleep quality and previous use of psychopharmaceuticals were significantly associated with physical, affective, as well as cognitive fatigue. Further, hot flashes were associated with increased physical and cognitive fatigue. In conclusion, the broad diagnosis "fatigue" in cancer survivors needs to be recognized as a diversity of symptoms determined by specific characteristics and likely different etiologies. Taking potential influencing factors such as obesity, physical inactivity, sleep problems, hot flashes, lack of social support, or psychological disorders into consideration might enable a better, individually-tailored fatigue treatment. This article is protected by copyright. All rights reserved.
PMID: 29082588 [PubMed - as supplied by publisher]
Bilateral Breast Cancer with Neurofibromatosis Type 1 Patient: Case Report.
Eur J Breast Health. 2017 Oct;13(4):213-215
Authors: Dursun D, Aktaş S, Altun Z, Olgun N
Abstract
Neurofibromatosis type 1 (NF1) is autosomal dominant and it is the most common hereditary disease. This case report is about a woman and her daughter. Both of them are NF1 and mother also has metachronous bilateral breast carcinoma. We analyzed expressions of 84 genes related with DNA Repair by Real Time PCR (AB Applied Biosystem 7000 Sequence Detection System; Thermo Fisher, Foster City, CA, USA). We also performed NF1 sequencing analyzing in exon 9 of the NF1 gene for mother. In Real Time PCR analysis of DNA Repair Genes, expression chances were predominant both in mother and daughter compared with control group. When the mother and daughter's expression profiles were compared, similar DNA repair array gene expression profiles were observed and the expression of DDB2, MGMT, MLH1, POLB UNG, XPA genes were high in both mother and daughter. In sequencing analysis, we obtained a mutation in c.1246 C>T. This mutation is reported to be common in NF1 cases with breast carcinoma. Our results indicate that the daughter with NF1 is probably prone to have malignancy in her future life. She should be carefully followed up for early diagnosis of a probable malignancy.
PMID: 29082380 [PubMed]
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Clinical implications of in silico mathematical modeling for glioblastoma: a critical review.
J Neurooncol. 2017 Oct 28;:
Authors: Protopapa M, Zygogianni A, Stamatakos GS, Antypas C, Armpilia C, Uzunoglu NK, Kouloulias V
Abstract
Glioblastoma remains a clinical challenge in spite of years of extensive research. Novel approaches are needed in order to integrate the existing knowledge. This is the potential role of mathematical oncology. This paper reviews mathematical models on glioblastoma from the clinical doctor's point of view, with focus on 3D modeling approaches of radiation response of in vivo glioblastomas based on contemporary imaging techniques. As these models aim to provide a clinically useful tool in the era of personalized medicine, the integration of the latest advances in molecular and imaging science and in clinical practice by the in silico models is crucial for their clinical relevance. Our aim is to indicate areas of GBM research that have not yet been addressed by in silico models and to point out evidence that has come up from in silico experiments, which may be worth considering in the clinic. This review examines how close these models have come in predicting the outcome of treatment protocols and in shaping the future of radiotherapy treatments.
PMID: 29081039 [PubMed - as supplied by publisher]
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MicroRNA Expression in Laser Micro-dissected Breast Cancer Tissue Samples - a Pilot Study.
Pathol Oncol Res. 2017 Oct 28;:
Authors: Seclaman E, Narita D, Anghel A, Cireap N, Ilina R, Sirbu IO, Marian C
Abstract
Breast cancer continues to represent a significant public health burden despite outstanding research advances regarding the molecular mechanisms of cancer biology, biomarkers for diagnostics and prognostic and therapeutic management of this disease. The studies of micro RNAs in breast cancer have underlined their potential as biomarkers and therapeutic targets; however most of these studies are still done on largely heterogeneous whole breast tissue samples. In this pilot study we have investigated the expression of four micro RNAs (miR-21, 145, 155, 92) known to be involved in breast cancer, in homogenous cell populations collected by laser capture microdissection from breast tissue section slides. Micro RNA expression was assessed by real time PCR, and associations with clinical and pathological characteristics were also explored. Our results have confirmed previous associations of miR-21 expression with poor prognosis characteristics of breast cancers such as high stage, large and highly proliferative tumors. No statistically significant associations were found with the other micro RNAs investigated, possibly due to the small sample size of our study. Our results also suggest that miR-484 could be a suitable endogenous control for data normalization in breast tissues, these results needing further confirmation by future studies. In summary, our pilot study showed the feasibility of detecting micro RNAs expression in homogenous laser captured microdissected invasive breast cancer samples, and confirmed some of the previously reported associations with poor prognostic characteristics of breast tumors.
PMID: 29081035 [PubMed - as supplied by publisher]
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Glutamine for the treatment of vincristine-induced neuropathy in children and adolescents with cancer.
Support Care Cancer. 2017 Mar;25(3):701-708
Authors: Sands S, Ladas EJ, Kelly KM, Weiner M, Lin M, Ndao DH, Dave A, Vahdat LT, Bender JG
Abstract
BACKGROUND: Vincristine is an integral treatment component of many childhood tumors with potentially dose-limiting sensory and/or motor neuropathy. Results from a pilot study on the incidence of vincristine-induced peripheral neuropathy (VIPN) as well as the efficacy and safety of glutamine in reducing signs and symptoms of VIPN in children with cancer are presented.
METHODS: Fifty-six patients between the ages of 5-21 with newly diagnosed leukemia, lymphoma, extracranial solid tumor or medulloblastoma and expected to receive a minimum cumulative dose of 6 mg/m(2) of vincristine over a 30-week period were eligible. Patients' neurological functioning was monitored every 3 weeks using clinical history, exam, and assessment of motor functioning. Upon identification of neuropathy, patients were randomized to either glutamine (6 g/m(2) per dose twice daily, maximum 10 g/dose) or placebo for a 3-week period followed by 3-week wash out period (Time 3).
RESULTS: Forty-nine patients were fully evaluable and 100 % developed neuropathy per study definitions. No significant differences in demographics or side effects were noted between the randomized groups. The distribution of sensory neuropathy scores between the two groups was statistically significant after the intervention (p = 0.022). Children receiving glutamine also rated their quality of life (QoL) as 8.42 points higher on the PedsQL total score than those receiving placebo (p = 0.031).
CONCLUSIONS: Glutamine supplementation is well tolerated and associated with improvements in sensory function and self-reported overall quality of life. Future studies are warranted to confirm the efficacy of glutamine for the treatment of vincristine-related sensory neuropathy in pediatric cancer patients.
PMID: 27830395 [PubMed - indexed for MEDLINE]