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Zarogoulidis P.,Aristotle University of Thessaloniki | Lampaki S.,Aristotle University of Thessaloniki | Francis Turner J.,Western Regional Medical Center | Huang H.,Shanghai University | And 3 more authors.
Oncology Letters | Year: 2014

Mammalian target of rapamycin (mTOR) is a protein serine/threonine kinase that was initially identified as the cellular target of rapamycin. This kinase regulates cell growth, proliferation, motility and survival, as well as the gene transcription and protein synthesis that are activated in response to hormones, growth factors and nutrients. Results from preclinical studies have indicated that factors antagonizing the mTOR pathway exert an antitumor effect on lung cancer. Furthermore, primary clinical trials of mTOR inhibitors have demonstrated that the inhibitors may be effective against lung carcinoma. The present study explores the association between mTOR and lung carcinogenesis and describes the clinical trials of mTOR inhibitors. © 2014, Spandidos Publications. All rights reserved.


PubMed | Western Regional Medical Center, National and Kapodistrian University of Athens, Aristotle University of Thessaloniki, Democritus University of Thrace and Shanghai University
Type: Journal Article | Journal: Oncology letters | Year: 2014

Mammalian target of rapamycin (mTOR) is a protein serine/threonine kinase that was initially identified as the cellular target of rapamycin. This kinase regulates cell growth, proliferation, motility and survival, as well as the gene transcription and protein synthesis that are activated in response to hormones, growth factors and nutrients. Results from preclinical studies have indicated that factors antagonizing the mTOR pathway exert an antitumor effect on lung cancer. Furthermore, primary clinical trials of mTOR inhibitors have demonstrated that the inhibitors may be effective against lung carcinoma. The present study explores the association between mTOR and lung carcinogenesis and describes the clinical trials of mTOR inhibitors.


PubMed | Helfgott Research Institute, Denver Naturopathic Clinic, Tahoma Clinic, Western Regional Medical Center and 4 more.
Type: Journal Article | Journal: Integrative cancer therapies | Year: 2016

Naturopathic oncology is a relatively new and emerging field capable of providing professional integrative or alternative services to cancer patients. Foundational research is critical to identify topics in the clinical and research development of naturopathic oncology for future growth of the field.This study implements a modified Delphi protocol to develop expert consensus regarding ethics, philosophy, and research development in naturopathic oncology.The modified protocol implements a nomination process to select a panel of 8 physicians and to assist in question formulation. The protocol includes an in-person discussion of 6 questions with multiple iterations to maintain the concept of the Delphi methodology as well as a postdiscussion consensus survey.The protocol identified, ranked, and established consensus for numerous themes per question. Underlying key topics include integration with conventional medicine, evidence-based medicine, patient education, patient safety, and additional training requirements for naturopathic oncologists.The systematic nomination and questioning of a panel of experts provides a foundational and educational resource to assist in clarification of clinical ethics, philosophy, and research development in the emerging field of naturopathic oncology.


PubMed | University of Pennsylvania, Germans Trias i Pujol Health science Institute and Hospital, Yale University, Western Regional Medical Center and 5 more.
Type: Journal Article | Journal: The Lancet. Oncology | Year: 2016

Anaplastic lymphoma kinase (ALK) gene rearrangements are oncogenic drivers of non-small-cell lung cancer (NSCLC). Brigatinib (AP26113) is an investigational ALK inhibitor with potent preclinical activity against ALK mutants resistant to crizotinib and other ALK inhibitors. We aimed to assess brigatinib in patients with advanced malignancies, particularly ALK-rearranged NSCLC.In this ongoing, single-arm, open-label, phase 1/2 trial, we recruited patients from nine academic hospitals or cancer centres in the USA and Spain. Eligible patients were at least 18 years of age and had advanced malignancies, including ALK-rearranged NSCLC, and disease that was refractory to available therapies or for which no curative treatments existed. In the initial dose-escalation phase 1 stage of the trial, patients received oral brigatinib at total daily doses of 30-300 mg (according to a standard 3+3 design). The phase 1 primary endpoint was establishment of the recommended phase 2 dose. In the phase 2 expansion stage, we assessed three oral once-daily regimens: 90 mg, 180 mg, and 180 mg with a 7 day lead-in at 90 mg; one patient received 90 mg twice daily. We enrolled patients in phase 2 into five cohorts: ALK inhibitor-naive ALK-rearranged NSCLC (cohort 1), crizotinib-treated ALK-rearranged NSCLC (cohort 2), EGFRBetween Sept 20, 2011, and July 8, 2014, we enrolled 137 patients (79 [58%] with ALK-rearranged NSCLC), all of whom were treated. Dose-limiting toxicities observed during dose escalation included grade 3 increased alanine aminotransferase (240 mg daily) and grade 4 dyspnoea (300 mg daily). We initially chose a dose of 180 mg once daily as the recommended phase 2 dose; however, we also assessed two additional regimens (90 mg once daily and 180 mg once daily with a 7 day lead-in at 90 mg) in the phase 2 stage. four (100% [95% CI 40-100]) of four patients in cohort 1 had an objective response, 31 (74% [58-86]) of 42 did in cohort 2, none (of one) did in cohort 3, three (17% [4-41]) of 18 did in cohort 4, and five (83% [36-100]) of six did in cohort 5. 51 (72% [60-82]) of 71 patients with ALK-rearranged NSCLC with previous crizotinib treatment had an objective response (44 [62% (50-73)] had a confirmed objective response). All eight crizotinib-naive patients with ALK-rearranged NSCLC had a confirmed objective response (100% [63-100]). Three (50% [95% CI 12-88]) of six patients in cohort 5 had an intracranial response. The most common grade 3-4 treatment-emergent adverse events across all doses were increased lipase concentration (12 [9%] of 137), dyspnoea (eight [6%]), and hypertension (seven [5%]). Serious treatment-emergent adverse events (excluding neoplasm progression) reported in at least 5% of all patients were dyspnoea (ten [7%]), pneumonia (nine [7%]), and hypoxia (seven [5%]). 16 (12%) patients died during treatment or within 31 days of the last dose of brigatinib, including eight patients who died from neoplasm progression.Brigatinib shows promising clinical activity and has an acceptable safety profile in patients with crizotinib-treated and crizotinib-naive ALK-rearranged NSCLC. These results support its further development as a potential new treatment option for patients with advanced ALK-rearranged NSCLC. A randomised phase 2 trial in patients with crizotinib-resistant ALK-rearranged NSCLC is prospectively assessing the safety and efficacy of two regimens assessed in the phase 2 portion of this trial (90 mg once daily and 180 mg once daily with a 7 day lead-in at 90 mg).ARIAD Pharmaceuticals.


PubMed | Aristotle University of Thessaloniki, Cancer Treatment Centers of America, Western Regional Medical Center and U.S. National Institutes of Health
Type: Journal Article | Journal: Case reports in oncology | Year: 2014

A 31-year-old white male with a known history of colon carcinoma was referred to the Interventional Pulmonary service for right lower lobe infiltrates and mucous plugging on computed tomography with concern for pneumonia. Bronchoscopy was performed revealing a broad based mass completely obstructing the bronchus intermedius. It was possible to pass a probe into the right lower lobe, and subsequent photoablation and mechanical debulking revealed that the mass was arising near the origin of the superior basal segment of the right lower lobe (RB6) and could be resected. Pathology confirmed this was consistent with the patients known primary colon carcinoma. The potential for endobronchial metastasis in patients with colorectal carcinoma should be investigated in those patients with new or worsening pulmonary symptoms and signs.


PubMed | University of Würzburg, Aristotle University of Thessaloniki, Goethe University Frankfurt, U.S. Army and 5 more.
Type: | Journal: OncoTargets and therapy | Year: 2015

Lung cancer remains the leading cause of death in cancer patients. Severe treatment side effects and late stage of disease at diagnosis continue to be an issue. We investigated whether local treatment using 2-diethylaminoethyl-dextran methyl methacrylate copolymer with p53 (DDMC-p53) with or without cisplatin and/or microwave ablation enhances disease control in BALBC mice. We used a Lewis lung carcinoma cell line to inoculate 140 BALBC mice, which were divided into the following seven groups; control, cisplatin, microwave ablation, DDMC-p53, DDMC-p53 plus cisplatin, DDMC-p53 plus microwave, and DDMC-p53 plus cisplatin plus microwave. Microwave ablation energy was administered at 20 W for 10 minutes. Cisplatin was administered as 1 mL/mg and the DDMC-p53 complex delivered was 0.5 mL. Increased toxicity was observed in the group receiving DDMC-p53 plus cisplatin plus microwave followed by the group receiving DDMC-p53 plus cisplatin. Infection after repeated treatment administration was a major issue. We conclude that a combination of gene therapy using DDMC-p53 with or without cisplatin and microwave is an alternative method for local disease control. However, more experiments are required in a larger model to identify the appropriate dosage profile.


PubMed | Cancer Treatment Centers of America, Western Regional Medical Center and Drexel University
Type: Journal Article | Journal: Case reports in oncology | Year: 2014

Cyclophosphamide is an alkylating agent widely used in antineoplastic and immunosuppressive therapies. Symptomatic hyponatremia can be a rare but life-threatening complication in patients treated with cyclophosphamide.We report 2 patients who presented with severe acute hyponatremic encephalopathy after receiving their first cycles of a low-dose cyclophosphamide-containing regimen for breast cancer. In case 1, a 58-year-old female received the combination of docetaxel and cyclophosphamide, and in case 2, a 56-year-old female received the combination of doxorubicin and cyclophosphamide. Both patients recovered after correction of their serum sodium concentration without neurological deficits. Future cycles of chemotherapy were well tolerated without recurrence of hyponatremia after cyclophosphamide was discontinued from the respective regimens.Clinicians must always keep in mind that acute hyponatremic encephalopathy can be induced by low-dose cyclophosphamide.


New findings that may impact patient care to be presented at annual World Conference on Lung Cancer (PHOENIX, Arizona - Dec. 6, 2016) - Lung cancer-based studies conducted at Cancer Treatment Centers of America® (CTCA) will be presented at the 17th International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer in Vienna, Austria, Dec. 4-7. These studies represent research conducted by members of the research team at Western Regional Medical Center led by Dr. Glen Weiss as they search for treatment options for varying types of lung cancer. "Lung cancer remains the leading cause of cancer-related death, and it is critical we commit research to ways in which we can identify new avenues for drug targets that may help more of these patients," said Dr. Weiss, Director of Clinical Research and Phase I and Phase II clinical trials at CTCA® at Western Regional Medical Center (Western). "It's an honor to be included among this year's participants at the World Conference on Lung Cancer," Weiss added. "It is our hope that this shared knowledge and research will benefit many lung cancer patients worldwide." More than 224,000 Americans will be diagnosed this year with some type of lung cancer, and more than 158,000 will succumb to this disease in 2016, making it by far the leading cause of cancer-related death in the U.S. For more details on these studies, visit: http://library. . For more information about CTCA trials currently available, visit http://www. , email WesternTrials@ctca-hope.com or call 888-841-9129. Cancer Treatment Centers of America Global, Inc. (CTCA), headquartered in Boca Raton, Fla., is a national network of five hospitals that serves adult patients who are fighting cancer. CTCA® offers an integrative approach to care that combines advancements in genomic testing and precision cancer treatment, surgery, radiation, immunotherapy and chemotherapy, with evidence-informed supportive therapies designed to help patients physically and emotionally by enhancing their quality of life while managing side effects both during and after treatment. CTCA serves patients from around the world at its hospitals in Atlanta, Chicago, Philadelphia, Phoenix and Tulsa. Consistently rated among U.S. hospitals that deliver the highest quality of care and patient experience, CTCA provides patients and their families with comprehensive information about their treatment options and encourages their active participation in treatment decisions. For more information, visit cancercenter.com, Facebook.com/cancercenter and Twitter.com/cancercenter.


Quan W.D.Y.,Western Regional Medical Center | Quan F.M.,Loma Linda University
Cancer Biotherapy and Radiopharmaceuticals | Year: 2014

Outpatient daily intravenous infusions of interleukin-2 (IL-2) have been developed to maintain anticancer activity and decrease toxicity of this agent against kidney cancer. Lymphokine activated killer cell (LAK) numbers are increased with these IL-2 schedules. Famotidine may enhance the LAK activity by increasing IL-2 internalization by the IL-2 receptor on lymphocytes. Fifteen patients with metastatic clear cell kidney cancer received IL-2 18 million IU/M2 intravenously over 15-30 minutes preceded by famotidine 20 mg IV daily for 3 days for 6 consecutive weeks as outpatients. Cycles were repeated every 8 weeks. Patient characteristics were seven males/eight females, median age 59 (range: 28-70), median Eastern Cooperative Oncology Group (ECOG) performance status-1; common metastatic sites were lungs (14), lymph nodes (9), liver (4), bone (4), and pancreas (4). Prior systemic therapies were oral tyrosine kinase inhibitor (8), IL-2 (6), and mTor inhibitor (2). Most common toxicities were rigors, arthralgia/myalgia, nausea/emesis, fever, and hypotension. All episodes of hypotension were reversible with intravenous fluid. No patients required hospitalization due to toxicity. One complete response (7%) and four partial responses (26%) were seen (total response rate=33%; 95% confidence interval: 15%-59%). Responses occurred in the lungs, liver, lymph nodes, and bone. Outpatient intravenous IL-2 with famotidine has activity in metastatic clear cell kidney cancer. © Mary Ann Liebert, Inc.


PubMed | Western Regional Medical Center
Type: Journal Article | Journal: Cancer biotherapy & radiopharmaceuticals | Year: 2014

Outpatient daily intravenous infusions of interleukin-2 (IL-2) have been developed to maintain anticancer activity and decrease toxicity of this agent against kidney cancer. Lymphokine activated killer cell (LAK) numbers are increased with these IL-2 schedules. Famotidine may enhance the LAK activity by increasing IL-2 internalization by the IL-2 receptor on lymphocytes. Fifteen patients with metastatic clear cell kidney cancer received IL-2 18 million IU/M intravenously over 15-30 minutes preceded by famotidine 20 mg IV daily for 3 days for 6 consecutive weeks as outpatients. Cycles were repeated every 8 weeks. Patient characteristics were seven males/eight females, median age 59 (range: 28-70), median Eastern Cooperative Oncology Group (ECOG) performance status-1; common metastatic sites were lungs (14), lymph nodes (9), liver (4), bone (4), and pancreas (4). Prior systemic therapies were oral tyrosine kinase inhibitor (8), IL-2 (6), and mTor inhibitor (2). Most common toxicities were rigors, arthralgia/myalgia, nausea/emesis, fever, and hypotension. All episodes of hypotension were reversible with intravenous fluid. No patients required hospitalization due to toxicity. One complete response (7%) and four partial responses (26%) were seen (total response rate=33%; 95% confidence interval: 15%-59%). Responses occurred in the lungs, liver, lymph nodes, and bone. Outpatient intravenous IL-2 with famotidine has activity in metastatic clear cell kidney cancer.

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