Search results for "22"

A common SNP in the UNG gene decreases ovarian cancer risk in BRCA2 mutation carriers

2018

Single nucleotide polymorphisms (SNPs) in DNA glycosylase genes involved in the base excision repair (BER) pathway can modify breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We previously found that SNP rs34259 in the uracil-DNA glycosylase gene (UNG) might decrease ovarian cancer risk in BRCA2 mutation carriers. In the present study, we validated this finding in a larger series of familial breast and ovarian cancer patients to gain insights into how this UNG variant exerts its protective effect. We found that rs34259 is associated with significant UNG downregulation and with lower levels of DNA damage at telomeres. In addition, we found that this SNP is associated with…

Childhood Cancer: Occurrence, Treatment and Risk of Second Primary Malignancies

2021

Simple Summary Childhood cancers are mostly of unknown etiology and represent devastating diagnoses. The clinical benefits of steadily increasing tumor control and survival rates are countered by severe and fatal health consequences from genotoxic therapies in long-term survivors of pediatric cancers. Among them, iatrogenic second primary malignancies represent the heaviest burden for the patient. Therefore, particularly in pediatric tumor patients, the reduction of genotoxic treatments and the use of targeted or immune-based oncologic strategies are of high clinical interest. The knowledge of therapy-associated as well as intrinsic risk factors for late sequelae of antineoplastic treatment…

A Pathology-Based Combined Model to Identify PAM50 Non-luminal Intrinsic Disease in Hormone Receptor-Positive HER2-Negative Breast Cancer

2019

No luminal; Subtipus intrínsec; Càncer de mama No luminal; Subtipo intrínseco; Cáncer de mama Non-luminal; Intrinsic subtype, Breast cancer Background: In hormone receptor-positive (HR+)/HER2-negative breast cancer, the HER2-enriched and Basal-like intrinsic subtypes are associated with poor outcome, low response to anti-estrogen therapy and high response to chemotherapy. To date, no validated biomarker exists to identify both molecular entities other than gene expression. Methods: PAM50 subtyping and immunohistochemical data were obtained from 8 independent studies of 1,416 HR+/HER2-negative early breast tumors. A non-luminal disease score (NOLUS) from 0 to 100, based on percentage of estr…

Fatal Liver and Bone Marrow Toxicity by Combination Treatment of Dichloroacetate and Artesunate in a Glioblastoma Multiforme Patient: Case Report and…

2016

A 52-year-old male patient was treated with standard radiochemotherapy with temozolomide for glioblastoma multiforme (GBM). After worsening of his clinical condition, further tumor-specific treatment was unlikely to be successful, and the patient seeked help from an alternative practitioner, who administered a combination of dichloroacetate (DCA) and artesunate (ART). A few days later, the patient showed clinical and laboratory signs of liver damage and bone marrow toxicity (leukopenia, thrombocytopenia). Despite successful restoration of laboratory parameters upon symptomatic treatment, the patient died 10 days after the infusion. DCA bears a well-documented hepatotoxic risk, while ART can…

The role of surgery in platinum-resistant ovarian cancer: A call to the scientific community.

2021

Abstract In the last decade, a growing attention has been focused on identifying effective therapeutic strategies also in the orphan clinical setting of women with platinum-resistant disease. In this context, secondary cytoreductive surgery (SCS) remains a potential approach only in women with platinum sensitive relapse, but experimental data have been published supporting the role of SCS also in patients with platinum-resistant recurrence. In particular, surgery is emerging as a potential option in specific subgroups of women, such as those patients with low-grade serous histology, or low-volume relapse with disease located in the so-called pharmacological sanctuaries. Furthermore, contras…

Abstract P1-19-46: A phase Ib dose escalation study evaluating the mutant selective PI3K-alpha inhibitor GDC-0077 (G) in combination with letrozole (…

2020

Abstract Background: Dysregulation of the PI3K/AKT/mTOR signaling pathway occurs in solid tumor malignancies. GDC-0077 (G) is a potent p110α-selective, p110α-mutant degrading inhibitor with anti-tumor activity in PIK3CA-mutant breast cancer xenograft models as a single agent and in combination with endocrine therapies (ET) with or without a CDK4/6 inhibitor (i). An open-label, Phase I dose escalation study of Galone and in combination with ET and P is underway in patients (pts) with locally advanced or metastatic PIK3CA-mutant solid tumors. Data from the combinations of G and L with and without P in pts with PIK3CA-mutant HR+/HER2- breast cancer are presented herein. Methods: This study (NC…

Accuracy of five intraocular lens formulas in eyes with trifocal lens implant.

2020

Accuracy of intraocular lens (IOL) calculation formulas SRK/T, Hoffer Q, Holladay 1, Haigis and Barrett Universal II were compared in prediction of postoperative refraction for multifocal and implants using a single optical biometry device. The authors included 88 refractive lens exchange and cataract surgeries, with AcrySof IQ PanOptix implant (Alcon Laboratories, Inc.). All eyes were divided into three groups based on axial length (AL), group 1: 24.5 mm (6 eyes). The refractive prediction error (RPE) and mean absolute error (MAE) were calculated for 5 different formulas: SRK/T, Hoffer Q, Holladay 1, Haigis and Barrett Universal II. For eyes with the AL between 22 mm and 24.5 mm the greate…

Repurposing of artemisinin-type drugs for the treatment of acute leukemia.

2020

Cancer treatment represents an unmet challenge due to the development of drug resistance and severe side effects of chemotherapy. Artemisinin (ARS)-type compounds exhibit excellent antimalarial effects with few side effects and drug-resistance. ARS and its derivatives were also reported to act against various tumor types in vitro and in vivo, including acute leukemia. Therefore, ARS-type compounds may be exquisitely suitable for repurposing in leukemia treatment. To provide comprehensive clues of ARS and its derivatives for acute leukemia treatment, their molecular mechanisms are discussed in this review. Five monomeric molecules and 72 dimers, trimers and hybrids based on the ARS scaffold …

2017

AbstractInterleukin-4 plays a critical role in the regulation of immune responses and has been detected at high levels in the tumour microenvironment of cancer patients, where concentrations correlate with the grade of malignancy. In prostate cancer, interleukin-4 has been associated with activation of the androgen receptor, increased proliferation and activation of survival pathways such as Akt and NF-κB. However, its role in therapy resistance has not yet been determined. Here we investigate the influence of interleukin-4 on primary epithelial cells from prostate cancer patients. Our data demonstrate an increase in the clonogenic potential of these cells when cultured in the presence of i…

Role of Surgical Versus Clinical Staging in Chemoradiated FIGO Stage IIB-IVA Cervical Cancer Patients—Acute Toxicity and Treatment Quality of the Ute…

2015

The Uterus-11 trial was designed to evaluate the role of surgical staging in patients with cervical cancer before primary chemoradiation therapy (CRT). The present report provides the toxicity data stratified by the treatment arm and technique.A total of 255 patients with carcinoma of the uterine cervix (International Federation of Gynecology and Obstetrics stage IIB-IVA) were randomized to either surgical staging followed by CRT (arm A) or clinical staging followed by CRT (arm B). Patients with para-aortic metastases underwent extended field radiation therapy (RT). Brachytherapy was mandatory. The present report presents the acute therapy-related toxicities stratified by treatment arm and …