Downregulation of IGF1R Expression Inhibits Growth and Enhances Cisplatin Sensitivity of Head and Neck Squamous Cell Carcinoma Cells In Vitro

Abstract

A lentivirus-mediated doxycycline-inducible pTRIPZ shRNAmir plasmid targeting IGF1R transcript was transfected into two head and neck squamous cell carcinoma (HNSCC) cell lines to silence IGF1R expression and to assess the effect of its downregulation on cisplatin sensitivity in vitro. In Cal27-regIGF1R and SCC25-regIGF1R cell lines, IGF1R protein expression was reduced by more than 90% after 72 h of incubation with doxycycline. Both basal and IGF-stimulated pIGF1R, pAKT, and pERK were significantly reduced, without influence on total AKT and ERK expression. Downregulation of the IGF1R was associated with decreased proliferation and cell viability in both cell lines. Reduced IGF1R expression was also associated with increased sub-G0/G1-phase and G0/G1-phase populations and decreased S-phase and G2/M-phase populations. IGF1R downregulation enhanced sensitivity to cisplatin with decrease of cisplatin IC₅₀ from 15 to 7.1 in Cal27-regIGF1R cells and from 11 to 6.3 in SCC25-regIGF1R cells. Cisplatin exhibited increased pro-apoptotic activity by annexin V staining and PARP cleavage in both cells lines when cultured in doxycycline. Thus, in two HNSCC cell lines in vitro, reduced IGF1R expression results in reduced growth rate and increased sensitivity to cisplatin. Thus, IGF1R downregulation and/or inhibition may serve as a useful adjunct to platinum-based cytotoxic chemotherapy.

https://ift.tt/2O3Vlu8

Safety of trifluridine/tipiracil in an open-label expanded-access program in elderly and younger patients with metastatic colorectal cancer

Abstract

Purpose

Trifluridine/tipiracil (FTD/TPI; TAS-102, Lonsurf®), a novel form of chemotherapy for metastatic colorectal cancer (mCRC), has shown clinical benefit in the global, phase III RECOURSE trial, regardless of patient age. Here, we report the safety and tolerability profile of FTD/TPI from an expanded-access program (EAP) in the US patients with mCRC whose disease has progressed on the standard therapies.

Methods

A total of 549 patients (≥ 18 years) with histologically confirmed mCRC following two or more regimens of standard therapy and an Eastern Cooperative Oncology Group performance status of 0 or 1 participated in this open-label EAP. During the 28-day treatment cycle, patients took FTD/TPI 35 mg/m² twice daily for 5 days followed by 2 days of rest for 2 weeks, with a 14-day rest period. Data were collected for therapy duration, treatment discontinuation, and adverse events. Age-based post hoc analysis was performed to determine the safety of FTD/TPI in elderly (≥ 65 years) versus younger (< 65 years) patients.

Results

FTD/TPI-treated patients in this EAP had a similar therapy duration and time to treatment discontinuation to those in the RECOURSE trial. The safety profile in elderly patients was consistent with that in younger patients, with no unexpected safety concerns.

Conclusions

This USA-based, open-label EAP has confirmed a similar safety and tolerability profile for FTD/TPI to that observed in the RECOURSE trial. Furthermore, FTD/TPI is well tolerated and can be considered as a treatment option in elderly patients with mCRC.

Trial registration

NCT02286492.

https://ift.tt/2R5lvi0

Left ventricular geometry and periodontitis in patients with the metabolic syndrome

Abstract

Objective

The presence of periodontal disease (PD) in subjects affected by the metabolic syndrome (MetS) may affect their risk of developing cardiovascular disease. The aim of this cross-sectional study was to investigate the systemic impact of PD in MetS, by assessing measures of sub-clinical atherosclerosis and left ventricular mass and geometry.

Materials and methods

A total of 103 patients undergoing treatment for MetS were examined for confirmation of diagnosis, blood sampling, and measures of pulse wave velocity (PWV), carotid intima-media thickness (c-IMT), left ventricular mass index (LVM), and relative wall thickness (RWT). All subjects underwent a detailed dental assessment, including measurements of DMFT (decayed-missing-filled teeth) and periodontal parameters.

Results

Ten patients (10%) were diagnosed with healthy-mild periodontitis, 38 patients (37%) were diagnosed in the moderate periodontitis group, and 55 (53%) had severe periodontitis. A total of 37% of subjects were affected by dental caries. Linear regression analysis revealed that patients with severe PD had increased average ventricular RWT (adjusted p = 0.032). Average full mouth probing pocket depth (PPD) was also associated with RWT (adjusted p = 0.006). No associations between PD and c-IMT, PWV, and LVM were detected after adjusted analyses.

Conclusion

This study suggests that periodontitis may be associated with concentric left ventricular remodeling, a predictive index of cardiovascular events.

Clinical relevance

The presence of periodontitis in patients with MetS might have an effect on left ventricular geometry. These findings stress the importance of prevention, diagnosis, and management of periodontitis in patients with MetS.

Trail registration

NCT03297749

https://ift.tt/2ysU2Qu

Letter to the Editor Regarding Diagnostic Accuracy of the McGill Thyroid Nodule Score in Pediatric Patients

Clinical Endocrinology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2R1WCDy

Role of fibroblast growth factor 21 in gestational diabetes mellitus: A mini‐review

Clinical Endocrinology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2q4InT9

Impact of Intraoperative Parathyroid Hormone Monitoring on the Management of Patients with Primary Hyperparathyroidism

Clinical Endocrinology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2R1Wq7i

Laparoscopic Hand Assisted Adrenalectomy for Tumours larger than 5cm

Clinical Endocrinology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2q85oV7

Bismuth‐containing quadruple therapy versus concomitant quadruple therapy as first‐line treatment for Helicobacter Pylori infection in an area of high resistance to clarithromycin: A prospective, cross‐sectional, comparative, open trial

Helicobacter, EarlyView.


https://ift.tt/2Ao4UAn

Pre-Operative Pregabalin for Post-Operative Pain in Head and Neck Cancer Surgery

Conditions:   Head and Neck Cancer;   Pain, Postoperative
Interventions:   Drug: Pregabalin 150mg;   Other: Placebo
Sponsor:   Augusta University
Not yet recruiting

https://ift.tt/2NVWDak

Study on Association Between Treatment of Allergic Rhinitis and Cognitive Ability in Children

Condition:   Allergic Rhinitis
Intervention:   Other: No intervention
Sponsor:   Chinese University of Hong Kong
Recruiting

https://ift.tt/2q7Lslf

Robotic-assisted Esophagectomy vs. Video-Assisted Thoracoscopic Esophagectomy(REVATE) Trial

Condition:   Esophageal Squamous Cell Carcinoma
Interventions:   Procedure: Robot esophagectomy (RE);   Procedure: Video-assisted thoracoscopic esophagectomy (VATE)
Sponsor:   Chang Gung Memorial Hospital
Not yet recruiting

https://ift.tt/2NVJ8HD

Stellate Ganglion Block in Head and Neck Cancer Surgery

Conditions:   Head and Neck Cancer;   Pain, Postoperative
Intervention:   Procedure: Stellate ganglion block
Sponsor:   Augusta University
Not yet recruiting

https://ift.tt/2q3LUB1

Exposure of remote organs and associated cancer risks from tangential and multi-field breast cancer radiotherapy

Abstract

Purpose

With the ever-increasing cure rates in breast cancer, radiotherapy-induced cancers have become an important issue. This study aimed to estimate secondary cancer risks for different treatment techniques, taking into account organs throughout the body.

Material and methods

Organ doses were evaluated for a tangential three-dimensional conformal (3D-CRT) and a multi-field intensity-modulated radiotherapy (IMRT) plan using a validated, Monte Carlo-based treatment planning system. Effects of wedges and of forward versus inverse planning were systematically investigated on the basis of phantom measurements. Organ-specific cancer risks were estimated using risk coefficients derived from radiotherapy patients or from the atomic bomb survivors.

Results

In the 3D-CRT plan, mean organ doses could be kept below 1 Gy for more remote organs than the lung, heart, and contralateral breast, and decreased to a few cGy for organs in the lower torso. Multi-field IMRT led to considerably higher mean doses in organs at risk, the difference being higher than 50% for many organs. Likewise, the peripheral radiation burden was increased by external wedges. No difference was observed for forward versus inverse planning. Despite the lower doses, the total estimated secondary cancer risk in more remote organs was comparable to that in the lung or the contralateral breast. For multi-field IMRT it was 75% higher than for 3D-CRT without external wedges.

Conclusion

Remote organs are important for assessment of radiation-induced cancer risk. Remote doses can be reduced effectively by application of a tangential field configuration and a linear accelerator set-up with low head scatter radiation.

https://ift.tt/2S8QRFF

Susceptibility mapping of the dural sinuses and other superficial veins in the brain

Publication date: Available online 21 October 2018

Source: Magnetic Resonance Imaging

Author(s): Sagar Buch, Yongsheng Chen, E. Mark Haacke

Abstract

Quantitative susceptibility mapping (QSM) is a means to obtain direct measurements of local tissue susceptibility distribution. Usually the focus is on imaging tissues in the brain, and the region of the brain studied is dictated by an eroded skull stripped mask. Producing the pristine local phase behavior for regions at the edge of the brain has been difficult in the past. For structures such as the superior sagittal sinus (SSS) that run alongside the surface of the brain and under the skull bones, a considerable part of the external phase from the dipole effect is lost due to the short T2* of the bones. In this paper, we propose a method that seeks to reconstruct the susceptibility distribution inside the dural sinuses by ensuring that the entire geometry of the dural sinuses is preserved with the help of an MR angiogram and venogram (MRAV). Having a geometrical model of the vessels makes it possible to estimate the missing phase outside the brain as well, by using the forward phase model and, hence, allowing a complete phase map to be reconstructed. Fifteen healthy volunteers were scanned using a susceptibility weighted imaging (SWI) sequence with interleaved rephased-dephased echoes. QSM results were compared between the conventional techniques and the proposed method of phase preservation outside the brain and inside the dural sinuses. This method demonstrates the reconstruction of the SSS, whereas conventional methods are either unable to preserve this structure or unable to provide complete phase information. The mean and standard deviation inside the SSS for all volunteers was 435 ± 5 ppb (this is the inter-subject error). To validate the proposed approach, the mean susceptibility inside the straight sinus showed good agreement between conventional approach and the proposed method. The results presented in this study indicate the potential of generating the susceptibility map for the whole brain, including the SSS (as well as potentially all the cortical veins).

https://ift.tt/2PM3d4R

Phase I trial of afatinib and 3-weekly trastuzumab with optimal anti-diarrheal management in patients with HER2-positive metastatic cancer

Abstract

Background

Trastuzumab is the mainstay of therapy for patients with HER2-positive breast and gastric cancer but resistance frequently occurs. Afatinib, an irreversible oral ErbB family blocker, shows clinical activity in trastuzumab-refractory HER2-positive metastatic breast cancer.

Materials and methods

This phase I study used a modified 3 + 3 dose escalation design to determine the maximum tolerated dose (MTD) of oral once-daily afatinib in combination with 3-weekly intravenous trastuzumab (8 mg/kg week 1; 6 mg/kg 3-weekly thereafter) for patients with confirmed advanced or metastatic HER2-positive cancer.

Results

Of the 13 patients treated, 6 received daily afatinib 20 mg and 7 received 30 mg. One patient who received afatinib 30 mg developed a tumor lysis syndrome and was not evaluable for dose-limiting toxicity (DLT). Two of the six remaining patients receiving afatinib 30 mg and 1 of the 6 patients receiving afatinib 20 mg experienced DLTs (all CTCAE ≥ grade 2 diarrhea despite optimal management) in the first treatment cycle. The most common drug-related adverse events were diarrhea (n = 13, 100%), asthenia (n = 8, 61.5%), rash (n = 7, 53.8%) and paronychia (n = 5, 38.5%). No pharmacokinetic interaction was observed. One patient (7.7%) had an objective response (20 mg afatinib cohort). Nine patients (69.2%) experienced clinical benefit.

Conclusions

Despite optimal management of diarrhea including treatment of grade I symptoms, it was not possible to treat the patients above a dose of 20 mg of afatinib daily in combination with 3-weekly trastuzumab. The MTD of afatinib in combination with the recommended 3-weekly dose of trastuzumab was 20 mg daily.

https://ift.tt/2NWpcEo

Scholar : Atlantic Studies, Volume 15, Issue 4, December 2018 is now available online on Taylor & Francis Online

The online platform for Taylor & Francis Online content Atlantic Studies, Volume 15, Issue 4, December 2018 is now available online on Taylor & Francis Online. This new issue contains the following articles: Articles "All shall be happy by land and by sea": Thomas Spence as an Atlantic thinker Matilde Cazzola Pages: 431-450 | DOI: 10.1080/14788810.2017.1372927 Print, religion and identity: The cultural significance of Thomas Gage Catherine Armstrong Pages: 451-475 | DOI: 10.1080/14788810.2017.1372968 A flexible quill: Abbé de Lahaye's role in late colonial Saint-Domingue, 1787–1791 – the legend and the life Chris Bongie Pages: 476-503 | DOI: 10.1080/14788810.2017.1422095 Flour for pesos: Precarious Atlantic financial interdependency and the provisioning of the Leclerc Expedition, 1802–1803 Cynthia A. Bouton Pages: 504-522 | DOI: 10.1080/14788810.2017.1411455 From fishery limits to limits to capital: Gendered appropriation and spectres of North Atlantic fishery collapse in The Silver Darlings and Sylvanus Now Michael Paye Pages: 523-538 | DOI: 10.1080/14788810.2017.1316462 The monarchical engagement of Portuguese immigrants in Brazil: A case of nineteenth-century transnational politics Isabel Corrêa da Silva Pages: 539-558 | DOI: 10.1080/14788810.2017.1410671 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Biophysical properties of striae rubra and striae alba in human skin: Comparison with normal skin

Skin Research and Technology, EarlyView.


https://ift.tt/2OGWEnR

The role of in vivo reflectance confocal microscopy in assessing the stability of vitiligo vulgaris prior to cellular grafting

Skin Research and Technology, EarlyView.


https://ift.tt/2NXuWxK

Micro‐relief analysis with skin capacitive imaging

Skin Research and Technology, EarlyView.


https://ift.tt/2OCNDfs

Water adsorption with relative humidity changes for keratin and collagen as studied by infrared (IR) micro‐spectroscopy

Skin Research and Technology, EarlyView.


https://ift.tt/2NW9064