Canagliflozin mediates tumor suppression alone and in combination with radiotherapy in non-small cell lung cancer (NSCLC) through inhibition of HIF-1α.

Non-small cell lung cancer (NSCLC) has a poor prognosis, and effective therapeutic strategies are lacking. The diabetes drug canagliflozin inhibits NSCLC cell proliferation and the mammalian target of rapamycin (mTOR) pathway, which mediates cell growth and survival, but it is unclear whether this drug can enhance response rates when combined with cytotoxic therapy. Here, we evaluated the effects of canagliflozin on human NSCLC response to cytotoxic therapy in tissue cultures and xenografts.

Review of brachytherapy complications - Upper gastrointestinal tract.

While brachytherapy applications are not widely used for cancer diagnoses in the upper GI tract (including the esophagus, liver, stomach, and pancreas), they have a clear role in palliation and symptom management and occasionally definitive locoregional treatment. With the increasing use of image-guided techniques, the incidence of side effects and complications has shown to be lower than many other alternative treatment modalities, making brachytherapy approaches a preferred treatment option. This review examines procedural complications and acute and chronic adverse effects from radiation associated with esophageal, hepatobiliary, and pancreatic brachytherapy and their management.

Low-dose non-targeted radiation effects in human esophageal adenocarcinoma cell lines.

Purpose: To investigate non-targeted radiation effects in esophageal adenocarcinoma cell lines (OE19 and OE33) using human keratinocyte and colorectal cancer cell reporters following γ-ray exposure.

Materials And Methods: Both clonogenic assays and ratiometric calcium endpoints were used to check for the occurrence of bystander signals in reporter cells.

Results: We report data suggesting that γ-irradiation increases cell killing over the expected linear quadratic (LQ) model levels in the OE19 cell line exposed to doses below 1 Gy, i.

Assessing patient characteristics and radiation-induced non-targeted effects in vivo for high dose-rate (HDR) brachytherapy.

Purpose: To test whether blood, urine, and tissue based colony-forming assays are a useful clinical detection tool for assessing fractionated treatment responses and non-targeted radiation effects in bystander cells.

Materials And Methods: To assess patients' responses to radiation treatments, blood serum, urine, and an esophagus explant-based in vivo colony-forming assay were used from oesophageal carcinoma patients. These patients underwent three fractions of high dose rate (HDR) intraluminal brachytherapy (ILBT).

Endotracheal brachytherapy alone: An effective palliative treatment for tracheal tumors.

Background: Tracheal tumors are rare. They are usually unresectable and treated primarily with external beam radiation. The use of palliative endotracheal brachytherapy (ETBT) alone in treating patients with tracheal tumors has not been reported.

The involvement of serum serotonin levels producing radiation-induced bystander effects for an in vivo assay with fractionated high dose-rate (HDR) brachytherapy.

Purpose: The primary goal of this investigation was to observe whether measurable levels of bystander factor(s) can be detected in esophageal carcinoma patients' urine samples taken after undergoing high dose rate (HDR) intraluminal brachytherapy (ILBT). However, a small pilot study was developed to evaluate whether serotonin [5-Hydroxytryptamine (5-HT)] serum levels play an active role in the mechanisms of radiation-induced bystander effects (RIBE) at high doses.

Materials And Methods: In the present study, a colony-forming in vivo assay was developed and used for the detection of non-targeted effects.

Adding external beam to intra-luminal brachytherapy improves palliation in obstructive squamous cell oesophageal cancer: a prospective multi-centre randomized trial of the International Atomic Energy Agency.

Background: Whether the combination of high dose-rate brachytherapy (HDRBT) and External Beam Radiation Therapy (EBRT) is superior to HDRBT alone for the palliation of oesophageal cancer has only been explored in a previous IAEA pilot randomized trial.

Methods: Two hundred and nineteen patients were randomized to adding EBRT or not, after receiving two fractions of HDRBT within 1 week. Each HDRBT consisted of 8 Gy prescribed at 1cm from source centre.

Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival.

Background: Previous results from our phase 3 randomised trial showed that adding cetuximab to primary radiotherapy increased overall survival in patients with locoregionally advanced squamous-cell carcinoma of the head and neck (LASCCHN) at 3 years. Here we report the 5-year survival data, and investigate the relation between cetuximab-induced rash and survival.

Methods: Patients with LASCCHN of the oropharynx, hypopharynx, or larynx with measurable disease were randomly allocated in a 1:1 ratio to receive either comprehensive head and neck radiotherapy alone for 6-7 weeks or radiotherapy plus weekly doses of cetuximab: 400 mg/m(2) initial dose, followed by seven weekly doses at 250 mg/m(2).

Motexafin gadolinium combined with prompt whole brain radiotherapy prolongs time to neurologic progression in non-small-cell lung cancer patients with brain metastases: results of a phase III trial.

Purpose: To determine the efficacy of motexafin gadolinium (MGd) in combination with whole brain radiotherapy (WBRT) for the treatment of brain metastases from non-small-cell lung cancer.

Methods And Materials: In an international, randomized, Phase III study, patients with brain metastases from non-small-cell lung cancer were randomized to WBRT with or without MGd. The primary endpoint was the interval to neurologic progression, determined by a centralized Events Review Committee who was unaware of the treatment the patients had received.

Preliminary report on the effect of brachytherapy on expression of p53, bc1-2 and apoptosis in squamous cell carcinoma of the oesophagus.

Pre-brachytherapy biopsies and post-brachytherapy oesophagectomy specimens of 10 patients with early squamous cell carcinoma of the middle third of the oesophagus were examined for the expression of p53, bcl-2 and apoptosis using immunohistochemical markers. There was no expression of p53 in one patient in both pre- and post-brachytherapy specimens. In 8 patients, p53 staining was strongly positive (3+) with approximately 50% or more cells, and with diffuse and no specific pattern in the pre-brachytherapy biopsies.

Prospective randomized trial of HDR brachytherapy as a sole modality in palliation of advanced esophageal carcinoma--an International Atomic Energy Agency study.

Background: Previous studies from South Africa have established that fractionated high-dose-rate (HDR) brachytherapy gives the best results in terms of palliation and survival in advanced esophageal cancer. A multicenter, prospective randomized study was therefore conducted under the auspices of the International Atomic Energy Agency to evaluate two HDR regimens.

Methods And Materials: Surgically inoperable patients with histologically proven squamous cell cancer of the esophagus, tumor >5 cm in length on barium swallow and/or endoscopy, Karnofsky performance score >50, age 17-70 years, primary disease in the thoracic esophagus, no prior malignancy within the past 5 years, and any N or M status were included in the study.