Isolated limb perfusion with melphalan, tumour necrosis factor-alpha and oncolytic vaccinia virus improves tumour targeting and prolongs survival in a rat model of advanced extremity sarcoma.

Isolated limb perfusion (ILP) is a treatment for advanced extremity sarcoma and in-transit melanoma. Advancing this procedure by investigating the addition of novel agents, such as cancer-selective oncolytic viruses, may improve both the therapeutic efficacy of ILP and the tumour-targeted delivery of oncolytic virotherapy. Standard in vitro assays were used to characterise single agent and combinatorial activities of melphalan, tumour necrosis factor-alpha (TNF-α) and Lister strain vaccinia virus (GLV-1h68) against BN175 rat sarcoma cells.

Optimising measles virus-guided radiovirotherapy with external beam radiotherapy and specific checkpoint kinase 1 inhibition.

Background And Purpose: We previously reported a therapeutic strategy comprising replication-defective NIS-expressing adenovirus combined with radioiodide, external beam radiotherapy (EBRT) and DNA repair inhibition. We have now evaluated NIS-expressing oncolytic measles virus (MV-NIS) combined with NIS-guided radioiodide, EBRT and specific checkpoint kinase 1 (Chk1) inhibition in head and neck and colorectal models.

Materials And Methods: Anti-proliferative/cytotoxic effects of individual agents and their combinations were measured by MTS, clonogenic and Western analysis.

Oncolytic reovirus type 3 (Dearing) as a novel therapy in head and neck cancer.

Introduction: Locally advanced head and neck cancer carries a poor prognosis, even with standard combination (surgery, radiotherapy, chemotherapy) treatment regimens. There is a pressing need for novel therapies with activity against this tumour type. Oncolytic reovirus type 3 (Dearing) is preferentially cytotoxic in tumour cells with an activated Ras signalling pathway and represents a promising novel therapy with relevance in head and neck cancer.

Reovirus exerts potent oncolytic effects in head and neck cancer cell lines that are independent of signalling in the EGFR pathway.

Background: Reovirus exploits aberrant signalling downstream of Ras to mediate tumor-specific oncolysis. Since ~90% squamous cell carcinomas of the head and neck (SCCHN) over-express EGFR and SCCHN cell lines are sensitive to oncolytic reovirus, we conducted a detailed analysis of the effects of reovirus in 15 head and neck cancer cell lines. Both pre- and post-entry events were studied in an attempt to define biomarkers predictive of sensitivity/resistance to reovirus.

Phase I/II trial of carboplatin and paclitaxel chemotherapy in combination with intravenous oncolytic reovirus in patients with advanced malignancies.

Purpose: Reovirus type 3 Dearing (RT3D) replicates preferentially in Ras-activated cancers. RT3D shows synergistic in vitro cytotoxicity in combination with platins and taxanes. The purpose of this phase I/II study was to assess RT3D combined with carboplatin/paclitaxel in patients with advanced cancers.

The need for third-line treatment in non-small cell lung cancer: an overview of new options.

As a result of improved effectiveness of first-, second-line and maintenance therapeutic regimens in non-small cell lung cancer, there is need for new options as third-line treatment. Erlotinib and gefitinib are currently the only drugs of proven efficacy in the third-line setting. Chemotherapy drugs, such as pemetrexed, are being investigated, as are many new agents, such as cetuximab, sunitinib, sorafenib, everolimus, enzastaurin, afilbercept.

Two-stage phase I dose-escalation study of intratumoral reovirus type 3 dearing and palliative radiotherapy in patients with advanced cancers.

Purpose: To determine the safety and feasibility of combining intratumoral reovirus and radiotherapy in patients with advanced cancer and to assess viral biodistribution, reoviral replication in tumors, and antiviral immune responses.

Experimental Design: Patients with measurable disease amenable to palliative radiotherapy were enrolled. In the first stage, patients received radiotherapy (20 Gy in five fractions) plus two intratumoral injections of RT3D at doses between 1 x 10(8) and 1 x 10(10) TCID(50).

Metastin is not involved in metastatic potential of non-small cell lung cancer.

Metastin, the product of the KISS-1 gene, seems to represent a strong suppressant of metastasis for some types of cancer. The aim of this study is to explore whether circulating levels of metastin could be used as a marker for the metastatic potential of non-small cell lung cancer (NSCLC) as well as a diagnostic marker in NSCLC patients. The possible correlation between metastin and leptin circulating levels was also evaluated.

Targeted therapeutic approaches for hormone-refractory prostate cancer.

Prostate cancer is one of the leading causes of cancer related death in men, and remains incurable in the metastatic setting. Despite the initial response to androgen deprivation, the disease gradually progresses to a hormone-refractory state due to cumulative genetic alterations in tumour cells or the microenvironment. Docetaxel represents the first chemotherapeutic agent with a small survival benefit for metastatic hormone-refractory prostate cancer (HRPC).

Carboplatin-pemetrexed adjuvant chemotherapy in resected non-small cell lung cancer (NSCLC): a phase II study.

Background: The aim of this study was to determine the progression-free survival (PFS) and toxicity associated with adjuvant administration of carboplatin and pemetrexed for completely resected patients with stage IB, II and IIIA non-small cell lung cancer (NSCLC).

Patients And Methods: Forty-five eligible NSCLC patients received surgical resection for pathological stage IB, II or IIIA followed by postoperative adjuvant chemotherapy with carboplatin AUC5 and pemetrexed administered on days 1 and 14 on a 28-day cycle. Recombinant human granulocyte colony-stimulating factor (rhG-CF) was given prophylactically.

Hypersensitivity reactions to oxaliplatin: a retrospective study and the development of a desensitization protocol.

Background: We recorded the epidemiologic and clinical features of hypersensitivity reactions (HSRs) to oxaliplatin in colorectal cancer (CRC) patients in order to provide information on the management of these patients. We also developed a desensitization protocol and evaluated its clinical application. For these reasons, we analyzed retrospectively the records of 215 CRC patients treated with oxaliplatin-containing regimens either as an adjuvant, first-line, second-line, or more.

The clinical significance of serum markers of bone turnover in NSCLC patients: surveillance, management and prognostic implications.

The purpose of this study was to investigate various serum markers of bone turnover in non-small cell lung cancer patients (NSCLC) in the presence or absence of bone metastasis. Our retrospective study included 79 newly diagnosed NSCLC patients. Group A included 51 patients with bone metastasis and group B included 28 patients that never developed bone metastasis.

Hypersensitivity reactions to oxaliplatin: a retrospective study and the development of a desensitization protocol.

Background: We recorded the epidemiologic and clinical features of hypersensitivity reactions (HSRs) to oxaliplatin in colorectal cancer (CRC) patients in order to provide information on the management of these patients. We also developed a desensitization protocol and evaluated its clinical application. For these reasons, we analyzed retrospectively the records of 215 CRC patients treated with oxaliplatin-containing regimens either as an adjuvant, first-line, second-line, or more.

Serum bone turnover markers may be involved in the metastatic potential of lung cancer patients.

The aim of this study was to investigate several bone markers in Non-Small Cell Lung (NSCLC) and Small Cell Lung (SCLC) patients experiencing or not secondary bony disease. Fasting serum levels of bone formation, bone resorption, and osteoclastogenesis markers were determined in 22 NSCLC patients with bone metastases, 18 without bone metastasis, and 28 SCLC patients. A total of 29 healthy volunteers were also included in the study.

Erlotinib-induced skin rash in patients with non-small-cell lung cancer: pathogenesis, clinical significance, and management.

The human epidermal growth factor receptor (EGFR) signaling is overexpressed in many solid malignancies, making it an appealing target for biologic agents. A number of agents that target this receptor are in use or in development. A specific adverse effect common to this class of agents is an acneiform-like skin rash that has been related to EGFR inhibition in the skin.

Therapy-induced toxicity of the lungs: an overview.

Unlabelled: Pulmonary toxicity induced by novel antineoplastic agents has not been well characterized because of the simultaneous or sequential use of drugs and a multimodality therapeutic approach. To further investigate this topic, relevant studies were identified through Medline. The generic names of novel antineoplastic agents and the key words pulmonary toxicity, dyspnea and pneumonitis were used for the search.

Increased serum levels of ghrelin at diagnosis mediate body weight loss in non-small cell lung cancer (NSCLC) patients.

Objective: Ghrelin is an orexigenic peptide implicated in body weight regulation, while cachexia is a multifactorial effect of non-small cell lung cancer (NSCLC) presented in patients with advanced disease. The aim of this study was to detect the role of ghrelin in cachexia and systemic inflammation of advanced NSCLC patients as well as its role as a diagnostic and prognostic tool.

Methods: Ghrelin serum levels were measured in 101 inoperable NSCLC patients before receiving any therapy (75 patients with weight loss and 26 without weight loss) and 60 healthy control volunteers.

Heat shock protein inhibitors and vaccines as new agents in cancer treatment.

Background: Heat shock proteins (HSP) play an essential role as molecular chaperones by assisting correct holding and folding in human cells. At the same time they present implications in tumor cell proliferation, differentiation, matrix invasion, angiogenesis, metastasis and cell death. They also possess the ability to present tumor molecules to the immune system and elicit an immune response.

Head and neck cancer in the elderly: an overview on the treatment modalities.

The percentage of elderly people with head and neck cancers (HNC) is rising due to increasing average lifespan. As with younger patients, elderly patients require a multidisciplinary approach in order to optimise treatment results. The biological, not the chronological, age should be defined individually based on co-morbidities and performance status.

The role of mTOR in the management of solid tumors: an overview.

Mammalian target of rapamycin (mTOR) is a key protein kinase controlling signal transduction from various growth factors and upstream proteins to the level of mRNA and ribosome with a regulatory effect on cell cycle progression, cellular proliferation and growth. TOR genes were discovered rather serendipitously while investigating the cause of resistance to immunosuppressant rapamycin in yeast. In normal cells, mTOR controls brilliantly the load of signals from its effectors resulting in a normal cell function.

Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) detection in cancer patients: a prognostic marker for lung metastases from solid malignancies.

Unlabelled: The aim of the study was to evaluate the serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) levels in breast, lung and colorectal cancer patients in correlation with clinical variables.

Patients And Methods: A total of 59 patients with a median age of 64 years and histologically confirmed breast 14, colorectal 15 or lung cancer 30 were evaluated. Five patients with breast cancer, 7 patients with colorectal cancer and 8 patients with lung cancer had lung metastases.

The significance of leptin, adiponectin, and resistin serum levels in non-small cell lung cancer (NSCLC).

Adipose tissue secretes adipokines with proinflammatory and anti-inflammatory properties. Our aim was to assess the role of adipose tissue in generalized inflammatory state of advanced NSCLC patients and the possible use of leptin, adiponectin and resistin as diagnostic and prognostic markers. Correlation of adipose tissue with weight loss in advanced NSCLC patients was also studied.