Prolonged complete response following gemcitabine-erlotinib combined therapy in advanced pancreatic cancer.

Pancreatic cancer is one of the most lethal types of malignant solid tumor and is typically associated with a poor prognosis. The majority of patients are diagnosed with advanced-stage disease, therefore, the median survival period is <6 months. Recently, a number of basic research projects and clinical trials were undertaken with the aim of improving treatment outcomes in pancreatic cancer; however, only one agent, erlotinib, passed the clinical trials. Erlotinib is an inhibitor of epidermal growth factor receptor, which when overexpressed in cancer, promotes angiogenesis, cell proliferation and inhibits apoptosis. The US Food and Drug Administration and European Medicines Agency approved erlotinib in combination with gemcitabine for the first-line treatment of advanced pancreatic cancer. To the best of our knowledge, the current study is the first to report a case of pancreatic cancer treated with this regimen alone to achieve a complete response (CR). A 40-year-old male with a medical history of chronic pancreatitis and hypertension was diagnosed with medically inoperable adenocarcinoma of the pancreas. Following palliative surgery, the patient began palliative gemcitabine and erlotinib chemotherapy. After three months, this treatment strategy resulted in a CR, as determined by imaging studies. Therapy was discontinued after 14 months due to the development of peritoneal metastases and the patient was referred for treatment with the folinic acid, 5-fluorouracil, irinotecan and oxaliplatin regimen. A CR is rarely reported in pancreatic cancer, however, a treatment strategy of gemcitabine and erlotinib may induce rapid regression of advanced-stage disease.

Impaired glucose metabolism treatment and carcinogenesis.

Carbohydrate metabolism disorders increase the risk of carcinogenesis. Diabetes mellitus alters numerous physiological processes that may encourage cancer growth. However, treating impaired glucose homeostasis may actually promote neoplasia; maintaining proper glucose plasma concentrations reduces metabolic stresses, however, certain medications may themselves result in oncogenic effects. A number of previous studies have demonstrated that metformin reduces the cancer risk. However, the use of sulfonylurea derivatives correlates with an increased risk of developing a malignancy. Another form of treatment, insulin therapy, involves using various forms of insulin that differ in pharmacodynamics, pharmacokinetics and efficacy. Previous studies have indicated that certain insulin variants also affect the cancer risk. The results from analyses that address the safety of long-lasting insulin types raise the most concern regarding the increased risk of malignancy. Rapid development of novel diabetic medications and their widespread use carries the risk of potentially increased rates of cancer, unnoticeable in limited, randomized, controlled trials. In the present review, the results of clinical and epidemiological studies are evaluated to assess the safety of anti-hyperglycemic medications and their effect on cancer risk and outcomes.

Molecular basis of carcinogenesis in diabetic patients (review).

The most important molecular mechanisms promoting carcinogenesis in patients with diabetes mellitus (DM) include oxidative stress, excessive generation of free radicals and nitrous oxide, damage to cellular membranes and DNA, overproduction of lactate, overabundance of protein glycosylation storage products, overexpression of pathological enzyme isoforms, and leakage of cytochromes from organelles. Additionally, dysfunctional signal transduction pathways, especially in pathways involving phosphoinositide 3­kinase (PI3K)/phosphatase and tensin homolog (PTEN)/Akt, RAS/Raf/ERK, and mammalian target of rapamycin (mTOR), have been implicated in malignant transformation and progression. Obesity and metabolic disorders, such as DM, may contribute to a dysfunctional immune system with a suppressed immune response by inducing a chronic inflammatory state, abnormal humoral and cellular mediated immunity, and lower counts and activity levels of natural killer (NK) cells and natural killer T cells (NKT cells). Recent advances in molecular biology will allow for better understanding of abnormal cellular pathways, as well as elucidating how metabolic disorders contribute to oncogenesis. Knowledge gained through these studies may lead to more efficacious oncologic therapies.

Tracheal adenoid cystic carcinoma mimicking a thyroid tumor: A case report.

At present, only eight cases of tracheal adenoid cystic carcinomas (ACCs) mimicking thyroid tumors have been reported. Since there are no guidelines available regarding their diagnosis and treatment, they present a significant clinical challenge. In the present study, patient treatment was analyzed to deliver the first concise summary of treatment options in patients with ACC mimicking a thyroid tumor. In addition, all available data regarding molecular abnormalities of this disease have been discussed. The current study presents a case of a 17-year-old patient with a tracheal ACC mimicking a thyroid tumor. The patient was diagnosed in 2007 with a pathological mass between the left lobe of the thyroid and the trachea, and underwent surgery and radiotherapy. In 2010, multiple lesions in the lungs were diagnosed and pulmonary metastasectomy was performed. Following surgery, the patient has been disease-free for almost 30 months. Thyroid tumor biopsy may reveal ACCs. This pathological report requires further investigation of the head and neck in order to confirm if the disease is of tracheal origin. Patients may present with a neck swelling, hoarseness of voice or dysphagia. Surgery must be considered as first-line therapy for all patients with local disease as it may be curative. For palliative treatment chemoradiotherapy based on cisplatin may be effective. The identification of cytogenetics, tumor suppressor genes, oncogenes, epigenetic alterations and mitochondrial abnormalities specific for ACCs is critical to the development of targeted therapies. Thus far, large studies have only reported the transcriptional activator Myb and mammalian target of rapamycin signaling pathway to be disrupted in ACCs.