Mutation-Targeted siRNA Therapy for Connexin 26-Associated Keratitis-Ichthyosis-Deafness Syndrome

ConclusionTo that end, a KID syndrome cell line (KID-KC) was established from primary keratinocytes of a KID syndrome patient with heterozygous p.D50N mutation, which displayed impaired gap junction intercellular communication and hyperactive hemichannels, confirmed by dye transfer, patch clamp and neurobiotin uptake assays. In KID-KCs, treatment with AS-siRNA led to robust inhibition of the mutant GJB2 allele without altering expression of the wildtype allele. This resulted in correction of both gap junction intercellular communication and hemichannel activity. Furthermore, AS-siRNA treatment caused only low-level off-target effects in KID-KCs, as detected by genome-wide RNA sequencing. Our data provide an important proof-of-concept for the potential use of AS-siRNA in treating KID syndrome, and in other genetic conditions due to dominant mutations.
Source: Cytotherapy - Category: Cytology Source Type: research

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Authors: Higashihara T, Okada A, Nakamura Y, Saigusa H, Homma S, Matsumura M, Kusano T, Shimizu A, Takano H Abstract We performed a renal biopsy for nephrotic syndrome in a patient with squamous cell lung carcinoma, which can worsen the prognosis. Chemoradiation therapy was effective for the cancer and proteinuria; we thus inferred that the nephrotic syndrome had been closely associated with the carcinoma. A pathological analysis of the kidney showed monoclonality for λ chain, satisfying the diagnostic criteria of proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID); however, con...
Source: Internal Medicine - Category: Internal Medicine Tags: Intern Med Source Type: research
ConclusionsThe results of this study showed that lung volume changes were not a cause for concern in breast cancer patients. There are three reasons to support this conclusion. Lung volume changes and percentage reductions in LVP for each Gy increase of MLD and each percentage increase of V20 in each lobe were small; patients were asymptomatic during the follow-up period; and LVP showed partial improvements after 6 months.
Source: Reports of Practical Oncology and Radiotherapy - Category: Cancer & Oncology Source Type: research
ConclusionUsing robust optimization for skin flash in breast IMRT planning is feasible. Further investigation is warranted to confirm the clinical effectiveness of this novel approach.
Source: Practical Radiation Oncology - Category: Cancer & Oncology Source Type: research
AbstractThe use of conventional chemotherapy in the treatment of cancer has been restricted by the lack of cell specificity, which causes toxicity regarding healthy cells resulting in limiting side effects responsible for low therapeutic efficiency. To overcome these drawbacks, the design of prodrugs has evolved and improved by covalently linking the drug through a degradable spacer. The use of these prodrugs as drug delivery systems, which are able to inactivate the drug during its biodistribution to specifically deliver the drug to its target, is an important breakthrough in cancer therapy. This strategy consisting in th...
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
ConclusionsThe exposure –response analysis suggested that intermittent 7-day veliparib 120 mg BID dosing in a 21-day cycle provided additional efficacy without meaningfully impacting the safety and tolerability when co-administered with carboplatin and paclitaxel in patients with BRCA-deficient breast cancer. A higher d ose of veliparib is unlikely to provide greater benefit in this combination in patients with BRCA-deficient recurrent or metastatic breast cancer.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
AbstractThioredoxin (Trx), thioredoxin reductase (TrxR), and NADPH are key members of the Trx system that is involved in redox regulation and antioxidant defense. In recent years, several researchers have provided information about the roles of the Trx system in cancer development and progression. These reports indicated that many tumor cells express high levels of Trx and TrxR, which can be responsible for drug resistance in tumorigenesis. Inhibition of the Trx system may thus contribute to cancer therapy and improving chemotherapeutic agents. There are now a number of effective natural and synthetic inhibitors with chemo...
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
Date: Wednesday, 10 16, 2019; Speaker: Rowan Chlebowski, MD, PhD, Chief and Senior Investigator, Harbor-UCLA Medical Center; Building: Building 10 (Clinical Center); Lipsett Amphitheater
Source: NIH Calendar of Events - Category: American Health Source Type: events
Date: Thursday, 11 14, 2019; Speaker: Ulrike Lorenz, Ph.D., Associate Professor, Dept. of Microbiology, Immunology, and Cancer Biology, University of Virginia; Building: Building 6B; 4B-429
Source: NIH Calendar of Events - Category: American Health Source Type: events
The prostate cancer community mourns the loss of Gerald Chodak, MD, an influential and iconic figure in urology.Medscape Urology
Source: Medscape Hematology-Oncology Headlines - Category: Cancer & Oncology Tags: Urology News Source Type: news
Abstract Skin cancer has become the most common type of cancer worldwide as a result of environmental exposure and medical treatments. A small group of patients are genetically predisposed to skin cancer and this article is intended as a diagnostic tool when encountering patients with multiple skin cancer lesions. The disorders are described with clinical characteristics, genetics and management. The most common syndromes associated with basal cell carcinoma are: Gorlin-Goltz syndrome, Rombo syndrome, and Bazex-Dupré-Christol syndrome. Multiple squamous cell carcinomas can be related to: xeroderma pigmentos...
Source: Acta Dermato-Venereologica - Category: Dermatology Authors: Tags: Acta Derm Venereol Source Type: research
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