Conserved Interferon-γ Signaling Drives Clinical Response to Immune Checkpoint Blockade Therapy in Melanoma.

We analyze the transcriptome of baseline and on-therapy tumor biopsies from 101 patients with advanced melanoma treated with nivolumab (anti-PD-1) alone or combined with ipilimumab (anti-CTLA-4). We find that T cell infiltration and interferon-γ (IFN-γ) signaling signatures correspond most highly with clinical response to therapy, with a reciprocal decrease in cell-cycle and WNT signaling pathways in responding biopsies. We model the interaction in 58 human cell lines, where IFN-γ in vitro exposure leads to a conserved transcriptome response unless cells have IFN-γ receptor alterations.

Interferon gamma, an important marker of response to immune checkpoint blockade in non-small cell lung cancer and melanoma patients.

Background: Programmed death-ligand 1 (PD-L1) may be induced by oncogenic signals or can be upregulated interferon gamma (IFN-γ). We have explored whether the expression of IFNG, the gene encoding IFN-γ, is associated with clinical response to the immune checkpoint blockade in non-small cell lung cancer (NSCLC) and melanoma patients. The role of inflammation-associated transcription factors STAT3, IKBKE, STAT1 and other associated genes has also been examined.

SEOM clinical guideline for the management of malignant melanoma (2017).

All melanoma suspected patients must be confirmed histologically and resected. Sentinel node biopsy must be done when tumor is over 1 mm or if less with high-risk factors. Adjuvant therapy with interferon could be offered for patients with high-risk melanoma and in selected cases radiotherapy can be added.

Local and systemic diffusion of antineoplastic drugs following vertebroplasty using acrylic cement mixed with cisplatin or methotrexate: experimental study in pigs.

Purpose: To determine the efficacy of cisplatin- or methotrexate-containing acrylic cement for local and systemic antineoplastic drug diffusion. Among the uses of acrylic cement or Polymethylmethacrylate (PMMA), there is the possibility to employ it as vehicle for drug diffusion. This capability is of interest in the treatment of pathological fractures: The curative effects of the cement (cytotoxicity of the monomer and increased temperature) are added to the antineoplastic effect of the drugs.

Pharmacogenetics and pharmacogenomics as tools in cancer therapy.

Pharmacogenetics and pharmacogenomics (PGx) are rapidly growing fields that aim to elucidate the genetic basis for the interindividual differences in drug response. PGx approaches have been applied to many anticancer drugs in an effort to identify relevant inherited or acquired genetic variations that may predict patient response to chemotherapy and targeted therapies. In this article, we discuss the advances in the field of cancer pharmacogenetics and pharmacogenomics, driven by the recent technological advances and new revolutionary massive sequencing technologies and their application to elucidate the genetic bases for interindividual drug response and the development of biomarkers able to personalize drug treatments.

SEOM guidelines for the management of Malignant Melanoma 2015.

All melanoma patients must be confirmed histologically and resected according to Breslow. Sentinel node biopsy must be done when tumor is over 1 mm or if less with high-risk factors. Adjuvant therapy with interferon must be offered for patients with high-risk melanoma and in selected cases radiotherapy can be added.

Melanoma early detection and awareness: how countries developing melanoma awareness programs could benefit from melanoma-proficient countries.

Risk factors for melanoma are well known and have guided plans for primary and secondary prevention. The presentation of the disease, however, varies widely depending on the geographic area, ethnicity, and socioeconomic status. For this reason, many countries have developed specific strategies to increase public awareness and favor early diagnosis.

Randomized pharmacokinetic study comparing subcutaneous and intravenous palonosetron in cancer patients treated with platinum based chemotherapy.

Background: Palonosetron is a potent second generation 5- hydroxytryptamine-3 selective antagonist which can be administered by either intravenous (IV) or oral routes, but subcutaneous (SC) administration of palonosetron has never been studied, even though it could have useful clinical applications. In this study, we evaluate the bioavailability of SC palonosetron.

Patients And Methods: Patients treated with platinum-based chemotherapy were randomized to receive SC or IV palonosetron, followed by the alternative route in a crossover manner, during the first two cycles of chemotherapy.

Adjuvant interferon alfa in malignant melanoma: an interdisciplinary and multinational expert review.

Interferon alfa (IFNα) and pegylated IFNα2b (PegIFNα2b) are the only agents currently approved for the adjuvant treatment of resected melanoma at high risk of recurrence. Meta-analyses showed statistically significant disease-free survival (DFS) and overall survival (OS) benefits versus controls but did not clarify optimal dose/duration. We review data from all recent clinical trials to provide the latest information on dose, duration, and potential predictive factors of treatment success.

[Extracorporeal circulation in no-cardiac surgery: experience at the Clinica Universidad de Navarra].

Aim: Analyse the use of the Extra-Corporeal Circulation (ECC) in no-cardiac operations at the Clinica Universidad de Navarra.

Material Of Study: Between 1985 and 2009, the ECC has been involved in 28 operations for retroperitoneal tumour with inferior vena cava thrombus, in 43 isolated hyperthermic perfusion of a limb for locally advanced cancer and in 8 cases of chest mass with invasion of the pulmonary veins or bronchial carina.

Results: The intraoperative mortality for renal cancer has been of 7% while the 28% of patients showed a major complication.

Immunotherapy of distant metastatic disease.

Immunotherapy of metastatic melanoma consists of various approaches leading to specific or non-specific immunomodulation. The use of FDA-approved interleukin (IL)-2 alone, in combination with interferon alpha, and/or with various chemotherapeutic agents (biochemotherapy) is associated with significant toxicity and poor efficacy that does not improve overall survival of 96% of patients. Many studies with allogeneic and autologous vaccines have demonstrated no clinical benefit, and some randomised trials even showed a detrimental effect in the vaccine arm.

Long-term results after resection for soft tissue sarcoma pulmonary metastases.

Isolated pulmonary metastases from soft tissue sarcomas (STS) occur in approximately 20% of the cases. Chemotherapy and surgical resection are the current standard treatment options for these patients. Our goal was to identify any prognostic factors for these patients as well as to estimate their long-term survival rate.

Fine-needle aspiration cytology and immunocytochemistry in the diagnosis of 24 gastrointestinal stromal tumors: a quick, reliable diagnostic method.

The diagnosis of gastrointestinal stromal tumors (GISTs) is generally established on histopathologic examination of surgical specimens. Fine-needle aspiration (FNA), performed under the guidance of ultrasound or computed tomography, is being used with increasing frequency in an attempt to diagnose primary and/or metastatic GISTs before surgery. The present study was undertaken to characterize the cytological appearance of these tumors and to assess the role of cytology, together with immunocytochemistry (ICC), in the diagnosis of GISTs.

Second-line chemotherapy with irinotecan and vinorelbine in stage IIIB and IV non-small-cell lung cancer: a phase II study.

The purpose of this study was to evaluate the efficacy and tolerance of combined irinotecan and vinorelbine in previously treated patients with stage IIIB and IV non-small-cell lung cancer (NSCLC). Thirty-three patients with NSCLC (7 stage IIIB and 26 stage IV) were enrolled. All had been previously treated with cisplatin, paclitaxel, and gemcitabine as first-line chemotherapy.

Oligonucleotides complementary to c-myb messenger RNA inhibit growth and induce apoptosis in human Burkitt lymphoma cells.

A 24-mer (antisense) phosphorothioate oligonucleotide (ODN) corresponding to the codons 2-9 of the c-myb gene was evaluated for its effects on the growth of a human Burkitt lymphoma cell line (Raji) in vitro. Raji cells incubated with different concentrations of c-myb antisense ODN (5-15 mu g/ml) for 24-72 h showed a significant dose-dependent decrease in growth. The same concentrations of control (sense) or scrambled c-myb phosphorothioate ODNs did not inhibit Raji cell growth.

Clinical trials with anticoagulant and antiplatelet therapies.

Clinical trials of drugs that influence coagulation and fibrinolysis pathways have been undertaken in patients with malignancy because these pathways are capable of influencing malignant progression. The validity of this concept was originally confirmed in experimental animal models of malignancy. Earlier pilot studies in human disease have been succeeded by definitive prospective randomized clinical trials that have revealed heterogeneity of responsiveness to anticoagulant and fibrinolytic agents that may be attributable to differences in mechanisms of interaction of the tumor cells of various types of malignancy with these pathways in vivo.

Oat cell carcinoma of the larynx. A study of six new cases.

Clinicopathological details of six oat cell carcinomas of the larynx are presented. Five patients were male and heavy smokers. Only two patients had lymph node metastases at diagnosis.

Undifferentiated epithelial-rich invasive malignant thymoma: complete response to cisplatin, vinblastine, and bleomycin therapy.

Two cases of complete remission plus one almost complete and another partial response of undifferentiated, invasive epithelial malignant thymoma using the combination of cisplatin, vinblastine, and bleomycin (PVB), are reported in four patients treated with this combination. Radiotherapy was instituted after completing the fourth course of chemotherapy in three patients. One patient died from intercurrent infection after the fourth cycle of combination chemotherapy.

Combination chemotherapy of cisplatin and 5-FU in advanced colorectal carcinoma.

Thirty-two patients with advanced colorectal carcinoma were treated with cisplatin (100 mg/m2) by infusion over 24 hours on Day 1 and 5-FU (1000 mg/m2/day) by infusion over 24 hours on Days 2-6 every 28 days. Ten of the 32 patients had received prior chemotherapy consisting of either 5-FU alone or 5-FU combination regimens. Objective response was observed in 13 patients (two complete and 11 partial responses).

Functional and ultrastructural studies of granulocyte adherence in the newborn.

Polymorphonuclear leukocyte (PMN) adherence to nylon was studied in the umbilical cord blood of 33 full-term, healthy newborns (NBs) during delivery. The results were compared to the adherence of PMN of peripheral blood in 50 healthy adult blood bank donors. PMN adherence in the NBs (56.