Systematic review of adoption, reporting and impact of health-related quality of life in phase III non-inferiority trials of systemic oncology treatments.

Background: Quality of life (QoL) assessment and patient-reported outcomes appear to be crucial in the rationale and interpretation of non-inferiority (NI) trials. The aim of this study was to assess the inclusion of QoL among endpoints in phase III NI oncology trials and the relevance of QoL results in the reporting and interpretation of these studies.

Materials And Methods: By PubMed search and hand-search of 11 selected journals, we identified phase III NI trials in adult patients affected by solid tumours, published between 2012 and 2021.

Gender-related differences in patients with carcinoid syndrome: new insights from an Italian multicenter cohort study.

Background: The incidence of neuroendocrine neoplasm (NEN) and related carcinoid syndrome (CaS) has increased markedly in recent decades, and women appear to be more at risk than men. As per other tumors, gender may be relevant in influencing the clinical and prognostic characteristics of NEN-associated CS. However, specific data on carcinoid syndrome (CaS) are still lacking.

Lynch syndrome-associated endometrial cancer patient with a rare novel germline likely pathogenic variant of MSH2 gene: A case report.

The Lynch syndrome (LS) is an autosomal dominant condition usually characterized by germline pathogenic variants in DNA mismatch repair (MMR) genes. Despite the guidelines now available, determining the pathogenicity of rare variants remains challenging, as the clinical significance of a genetic variant could be uncertain, but it may represent a disease-associated variation in the aforementioned genes. In this case report we will describe the case of a 47 years-old female affected by endometrial cancer (EC) with an extremely rare germline heterozygous variant in the MSH2 gene (c.

Catheter-related complications in onco-hematologic children: A retrospective clinical study on 227 central venous access devices.

Background: The use of central venous access devices (CVADs) is of paramount importance to safely deliver antiblastic and support therapies in children with cancer. Though, in pediatric patients, as much as in adults, CVADs are potentially associated with severe complications which may result in unscheduled interruption of therapy, hospitalization, increased morbidity/mortality, and increased cost of care.

Methods: We have reviewed retrospectively our experience with CVADs in children with solid tumors and hematologic diseases, with the purpose of verifying if the adoption of well-defined insertion and maintenance bundles might be effective in reducing catheter-related complications, and in particular catheter-related thrombosis.

Intratumoral delivery of docetaxel enhances antitumor activity of Ad-p53 in murine head and neck cancer xenograft model.

Purpose: The aim of this study is to determine the ability of intratumorally delivered docetaxel to enhance the antitumor activity of adenovirus-mediated delivery of p53 (Ad-p53) in murine head and neck cancer xenograft model.

Materials And Methods: A xenograft head and neck squamous cell carcinoma mouse model was used. Mice were randomized into 4 groups of 6 mice receiving 6 weeks of biweekly intratumoral injection of (a) diluent, (b) Ad-p53 (1 x 10(10) viral particles per injection), (c) docetaxel (1 mg/kg per injection), and (d) combination of Ad-p53 (1 x 10(10) viral particles per injection) and docetaxel (1 mg/kg per injection).

An acute toxicology study with INGN 007, an oncolytic adenovirus vector, in mice and permissive Syrian hamsters; comparisons with wild-type Ad5 and a replication-defective adenovirus vector.

Oncolytic (replication-competent) adenoviruses as anticancer agents provide new, promising tools to fight cancer. In support of a Phase I clinical trial, here we report safety data with INGN 007 (VRX-007), an oncolytic adenovirus with increased anti-tumor efficacy due to overexpression of the adenovirus-encoded ADP protein. Wild-type adenovirus type 5 (Ad5) and a replication-defective version of Ad5 were also studied as controls.

INGN 007, an oncolytic adenovirus vector, replicates in Syrian hamsters but not mice: comparison of biodistribution studies.

Preclinical biodistribution studies with INGN 007, an oncolytic adenovirus (Ad) vector, supporting an early stage clinical trial were conducted in Syrian hamsters, which are permissive for Ad replication, and mice, which are a standard model for assessing toxicity and biodistribution of replication-defective (RD) Ad vectors. Vector dissemination and pharmacokinetics following intravenous administration were examined by real-time PCR in nine tissues and blood at five time points spanning 1 year. Select organs were also examined for the presence of infectious vector/virus.

Dialysis and concentration of protein solutions.

Conventional dialysis separates small molecules from large molecules by allowing diffusion of only the small molecules through selectively permeable membranes. This appendix describes dialysis of large- and small-volume samples using cellulose membranes with pore sizes designed to exclude molecules above a selected molecular weight. A Support Protocol describes preparation of membranes for dialysis and discusses issues related to the selection of membranes including commercial kits.

Dialysis.

This appendix describes dialysis of large- and small-volume samples using cellulose membranes with pore sizes designed to exclude molecules above a selected molecular weight. A support protocol describes preparation of membranes for dialysis.

Dialysis and ultrafiltration.

The first section of this unit describes dialysis of large- and small-volume samples using cellulose membranes with pore sizes designed to exclude molecules above a selected molecular weight. A support protocol describes preparation of membranes for dialysis. The second section describes protocols for ultrafiltration, and the third section describes simple methods of concentrating solutions.

Dialysis and concentration of protein solutions.

Conventional dialysis separates small molecules from large molecules by allowing diffusion of only the small molecules through selectively permeable membranes. Dialysis is usually used to change the salt (small-molecule) composition of a macromolecule-containing solution. This unit describes dialysis of large- and small-volume samples using cellulose membranes with pore sizes designed to exclude molecules above a selected molecular weight.

p53 therapy in a patient with Li-Fraumeni syndrome.

Li-Fraumeni syndrome is an autosomal dominant disorder that greatly increases the risk of developing multiple types of cancer. The majority of Li-Fraumeni syndrome families contain germ-line mutations in the p53 tumor suppressor gene. We describe treatment of a refractory, progressive Li-Fraumeni syndrome embryonal carcinoma with a p53 therapy (Advexin) targeted to the underlying molecular defect of this syndrome.

Adenoviral-mediated PTEN expression radiosensitizes non-small cell lung cancer cells by suppressing DNA repair capacity.

Expression of the PTEN tumor suppressor gene is abnormal in many human cancers. Loss of PTEN expression leads to the activation of downstream signaling pathways that have been associated with resistance to radiation. In non-small cell lung carcinoma (NSCLC), suppressed expression of PTEN is frequently due to methylation of its promoter region.

Enhancement of Ad-p53 therapy with docetaxel in head and neck cancer.

Objective: The objective of this project was to determine the mechanisms in which docetaxel enhances Ad-p53 tumor suppressive effects in head and neck cancer.

Background: In advanced head and neck squamous cell carcinoma (HNSCC), the 5-year survival rate is less than 40%. Because patients with advanced HNSCC have a high rate of local-regional failure (40-60%) with existing treatment modalities, aggressive local therapy approaches need to be developed.

5-Fluorouracil or gemcitabine combined with adenoviral-mediated reintroduction of p16INK4A greatly enhanced cytotoxicity in Panc-1 pancreatic adenocarcinoma cells.

Background: Pancreatic cancer is one of the most lethal of all the common gastrointestinal malignancies. Although surgery offers the best chance for survival, it is not appropriate for all cases. The only adjuvant treatment to show promise is chemotherapy.

Adenovirus-mediated PTEN treatment combined with caffeine produces a synergistic therapeutic effect in colorectal cancer cells.

The tumor suppressor phosphatase and tensin homologue deleted from chromosome 10 (PTEN) gene is a negative regulator of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt/PKB) signaling pathway. Overexpression of PTEN in cancer cells results in cell-cycle arrest and cell death through inhibition of PI3K. Caffeine, a xanthine analogue, is well known to enhance the cytocidal and growth-inhibitory effects of DNA-damaging agents such as radiation, UV light, and anticancer agents on tumor cells by abrogating DNA-damage checkpoints through inhibition of ataxia-telangiectasia-mutated (ATM), and ATM and Rad3-related (ATR) kinase activity.

Adenovirus-mediated transfer of the PTEN gene inhibits human colorectal cancer growth in vitro and in vivo.

The tumor-suppressor gene PTEN encodes a multifunctional phosphatase that is mutated in a variety of human cancers. PTEN inhibits the phosphatidylinositol 3-kinase pathway and downstream functions, including activation of Akt/protein kinase B (PKB), cell survival, and cell proliferation in tumor cells carrying mutant- or deletion-type PTEN. In such tumor cells, enforced expression of PTEN decreases cell proliferation through cell-cycle arrest at G1 phase accompanied, in some cases, by induction of apoptosis.

PI3 kinase blockade by Ad-PTEN inhibits invasion and induces apoptosis in RGP and metastatic melanoma cells.

Background: Melanoma is an aggressive tumor with a propensity to rapidly metastasize. The PTEN gene encodes a phosphatase with an unusual dual specificity for proteins and lipids. Mutations of PTEN have been found in various human cancers, including glioblastoma, prostate, breast, lung, and melanoma.

Inhibition of human lung cancer growth following adenovirus-mediated mda-7 gene expression in vivo.

Overexpression of the melanoma differentiation associated gene-7 (mda-7) in vitro results in suppression of lung cancer cell proliferation. However, the ability of MDA-7 to suppress lung cancer in vivo has not been previously demonstrated. In this study, we investigated the possibility of inducing overexpression of the mda-7 gene in human non-small cell lung carcinoma cells in vivo and its effects on tumor growth.

Phosphatase and tensin analog gene overexpression engenders cellular death in human malignant mesothelioma cells via inhibition of AKT phosphorylation.

Background: Abnormal phosphatase and tensin analog (PTEN) gene expression has been noted in neoplasms. The PTEN protein cleaves phosphate groups from cellular growth kinases, inhibiting tumor propagation. A downstream target of PTEN is AKT, a serine-threonine kinase that when activated inhibits apoptosis.

Dialysis and concentration of protein solutions.

Conventional dialysis separates small molecules from large molecules by allowing diffusion of only the small molecules through selectively permeable membranes. Dialysis is usually used to change the salt (small-molecule) composition of a macromolecule-containing solution. The solution to be dialyzed is placed in a sealed dialysis membrane and immersed in a selected buffer; small solute molecules then equilibrate between the sample and the dialysate.

Adenovirus-mediated transfer of p53 and p16(INK4a) results in pancreatic cancer regression in vitro and in vivo.

Pancreatic cancer has a very poor prognosis. Current chemotherapy and radiotherapy regimens are only moderately successful. The tumour suppressor genes p53 and p16(INK4a)encode cell cycle regulatory proteins that are important candidates for gene replacement therapy.

Adenovirus-mediated wild-type p53 gene expression radiosensitizes non-small cell lung cancer cells but not normal lung fibroblasts.

Purpose: We compared the ability of adenoviral-mediated wild-type p53 RPR/INGN201(Ad5/CMV/p53) to radiosensitize non-small cell lung carcinoma (NSCLC) and normal lung fibroblast cells.

Materials And Methods: NSCLC cell lines (A549 and H322) and human lung fibroblast cells (MRC-9 and CCD-16) were used in this study. Radiosensitivity was determined by clonogenic assay and tumor growth delay.

Bivariate analysis of the p53 pathway to evaluate Ad-p53 gene therapy efficacy.

Background: Gene therapy of human tumors with adenovirus vectors presents a clinical research challenge and a potential opportunity in cancer therapy. One of the research challenges is that endpoints like tumor reduction, time to recurrence, and survival do not provide information about whether a potential therapeutic infects the targeted cells or whether the transferred gene functions or induces a cellular response. Therefore, a flow cytometric approach was developed for a wildtype, p53 encoding adenoviral vector (Ad-p53) that provides (1) the relative level of p53 transferred by p53 immunoreactivity, (2) mdm2 immunoreactivity as an assay of p53 activity, and (3) estimates of the percentage of infected cells by dual parameter analysis (p53 versus mdm2).