Anti-inflammatory mechanisms in cancer research: Characterization of a distinct M2-like macrophage model derived from the THP-1 cell line.

Aims: Macrophages play an essential role in cancer development. Tumor-associated macrophages (TAMs) have predominantly M2-like attributes that are associated with tumor progression and poor patient survival. Numerous methods have been reported for differentiating and polarizing macrophages in vitro, but there is no standardized and validated model for creating TAMs.

Obesity hormones and itaconate mediating inflammation in human colon cancer cells - Another lead to early-onset colon cancer?

Background: Chronic inflammation is a key feature of obesity and a hallmark of colon cancer (CC). The obesity-related hormones leptin and adiponectin alter inflammatory gene profiles in cancer, but their specific role in CC is unclear. We have previously studied the effects of leptin and the macrophage-specific mediator itaconate on M2-like macrophages.

Mask On, Mask Off: Risk Perceptions for COVID-19 and Compliance with COVID-19 Safety Measures.

Since early 2020, COVID-19 has spread throughout the United States (US), killing more than 700,000. Mask-wearing, social-distancing, and hand hygiene can curb the spread of COVID-19 and other infectious diseases. However, the adherence to COVID-19 safety measures varies considerably among the US public, likely due to disparate perceptions of COVID-19's risk.

Itaconate and leptin affecting PPARγ in M2 macrophages: A potential link to early-onset colorectal cancer.

Background: Along with the rising incidence of obesity, there has been an increase in patients diagnosed with early-onset colorectal cancer (<50 years old). In colorectal cancer, worse patient survival is associated with certain cytokine expression and downregulation of peroxisome proliferator activated receptor gamma expression. The effects of the obesity hormone leptin and macrophage-specific metabolite itaconate on these mechanisms are poorly understood.

Macrophage Differentiation and Polarization into an M2-Like Phenotype using a Human Monocyte-Like THP-1 Leukemia Cell Line.

Tumor-associated macrophages (TAM) can switch their expression and cytokine profile according to external stimuli. This remarkable plasticity enables TAM to adapt to ongoing changes within the tumor microenvironment. Macrophages can have either primarily pro-inflammatory (M1-like) or anti-inflammatory (M2-like) attributes and can continually switch between these two main states.

Cutaneous oncocytoma - a report of three cases and review of the literature.

The oncocyte is a cell characterized by capacious, eosinophilic, finely granular cytoplasm, and lesions composed primarily of oncocytes are termed oncocytomas. Whereas oncocytic metaplasia has been reported in various cutaneous neoplasms, oncocytomas typically occur in the kidneys, thyroid and salivary glands and are uncommon in the dermatopathology literature. We present three cases of cutaneous oncocytoma so that dermatopathologists are cognizant of this uncommon entity.

On modelling the flow controls on macrophyte and epiphyte dynamics in a lowland permeable catchment: the River Kennet, southern England.

A new in-stream model of phosphorus (P) and macrophyte dynamics, the Kennet Model, was applied to a reach of the River Kennet to investigate the impacts of changing flow conditions on macrophyte growth. The investigation was based on the assessment of two flow change scenarios, which both included the simulation of decreasing total phosphorus concentrations from a sewage treatment works due to improved effluent treatment. In the first scenario, the precipitation and potential evaporation outputs from a climate change model (HadCM2 GGx) where input into the catchment model INCA to predict the mean daily flows in the reach.

Macrophyte and periphyton dynamics in a UK Cretaceous Chalk stream: the river Kennet, a tributary of the Thames.

An initial study to observe the seasonal trends and to determine the factors influencing macrophyte and periphyton growth patterns was undertaken on a representative reach of the River Kennet (UK) over a 2-year period (1998-2000). Maximum average macrophyte and average periphyton dry matter biomass recorded during the growing season were 200 and 21 g m(-2), respectively. The relationships between macrophyte and periphyton percentage cover and biomass data with physico-chemical variables were investigated.

Evaluation of pulmonary alveolar epithelial integrity by the detection of restriction to diffusion of hydrophilic solutes of different molecular sizes.

The rate of transfer of a hydrophilic solute from the alveoli to pulmonary blood following inhalation as an aerosol depends on the molecular size of the solute and the permeability of the alveolar epithelium. The value of this measurement for assessing damage to the epithelium in lung disease is compromised by cigarette smoking, which accelerates clearance by unknown mechanisms. The rates of clearance of (99m)Tc-labelled diethylenetriaminepenta-acetic acid (DTPA) (molecular mass 492 Da) and (113m)In-labelled biotinylated DTPA (B-DTPA) (molecular mass 1215 Da) were monitored simultaneously by dynamic gamma-radiation camera imaging following simultaneous inhalation, and compared between eight normal non-smoking subjects and nine habitual cigarette smokers.

Direct technetium-99m labeling of three anticancer monoclonal antibodies: stability, pharmacokinetics and imaging.

Unlabelled: Monoclonal antibodies (MAbs) directly labeled with 99mTc have been used in a number of clinical immunoscintigraphic investigations. Three anti-cancer MAbs were radiolabeled with 99mTc using a reduction-mediated technique. The stability, biodistribution and in vivo pharmacokinetics were assessed and compared with the same antibodies labeled with 125I.

Anti-chelate antibodies after intraperitoneal yttrium-90-labeled monoclonal antibody immunoconjugates for ovarian cancer therapy.

Unlabelled: The development of stable chelating agents for metal isotopes (e.g., 90Y) such as CITC-DTPA, a benzyl-analog of DTPA, allowed us to evaluate the efficacy of 90Y-labeled HMFG1 MAb administered intraperitoneally in patients with ovarian cancer.

90Y-labeled antibody uptake by human tumor xenografts and the effect of systemic administration of EDTA.

Purpose: A human tumor xenograft model was used to compare the tumor and normal tissue uptake of a tumor-associated monoclonal antibody radiolabeled with 125I or 90Y.

Methods And Materials: Nude mice bearing SC xenografts of the human colon adenocarcinoma, HT29, were injected with a mixture of 125I- and 90Y-DTPA-labeled AUA1 monoclonal antibody, which recognizes an antigen expressed on the surface of the tumor cells. In addition, the effect of systemic ethylenediaminetetraacetic acid (EDTA) administration on 90Y-labeled antibody clearance, tumor uptake of antibody and bone accumulation of 90Y was studied in a nude mouse model of intraperitoneal cancer.

Pharmacokinetics and toxicity of an yttrium-90-CITC-DTPA-HMFG1 radioimmunoconjugate for intraperitoneal radioimmunotherapy of ovarian cancer.

Background: The intracavitary route for the administration of monoclonal antibodies is used in a variety of locally spreading cancers. The authors have been treating patients with ovarian cancer in Phase I and II studies assessing toxicity and response to improved radioimmunoconjugates.

Methods: Nineteen patients, 34-65 years of age, were treated with a new radioimmunoconjugate, 90Y-CITC-DTPA-HMFG1, instilled in the peritoneal cavity after second-look laparoscopy.

Targeting of tumours with murine and reshaped human monoclonal antibodies against placental alkaline phosphatase: immunolocalisation, pharmacokinetics and immune response.

Anti-tumour monoclonal murine and humanised (reshaped human) antibodies (H17E2 and Hu2PLAP, respectively) against placental alkaline phosphatase (PLAP), radioactively labelled with indium-111 (111In) and iodine-123 (123I), were evaluated for their ability to localise mainly testicular and ovarian tumours in sequential pilot studies of the Hammersmith Oncology Group. 33 patients with active primary and/or metastatic testicular cancer were studied with the [111In]- or [123I]H17E2 antibody. 8 patients with testicular cancer were studied with the same antibody after being rendered free of disease after induction chemotherapy and surgical resection of residual tumour.

Adjuvant therapy of ovarian cancer with radioactive monoclonal antibody.

Fifty-two patients with epithelial ovarian cancer were treated with yttrium-90-labelled monoclonal antibody HMFG1 administered intraperitoneally following conventional surgery and chemotherapy as part of an extended phase I-II trial. The treatment was well tolerated and the only significant toxicity observed was reversible myelosuppression as previously described. Following conventional surgery and chemotherapy, 21 out of the 52 patients had no evidence of residual disease and were regarded as receiving treatment in an adjuvant setting.

Technetium-99m-labeled antibodies. Stability compared to 125I labeled antibodies.

It is essential in any method for radiolabeling antibody with 99mTc that the labeling procedure is rapid and reliable, producing a highly stable 99mTc-antibody complex with minimal effect on the immunoreactivity of the antibody. In the present study, analysis of the stability and homogeneity of radiolabeled (99mTc and 125I) antibodies (HMFG1 and PR1A3) was carried out by fast protein liquid chromatography (FPLC) using superose-6 and S-200 columns, and by polyacrylamide gel electrophoresis (PAGE) followed by autoradiography. Superose 6 and S-200 gel filtration analysis showed the radiolabel (99mTc or 125I) eluting with a retention time identical to that of native antibody.

Development of humoral immune responses against a macrocyclic chelating agent (DOTA) in cancer patients receiving radioimmunoconjugates for imaging and therapy.

The development of stable immunoconjugates by the advent of macrocyclic metal chelating agents (DOTA) has enabled us to study the ability of 111In-DOTA-labeled monoclonal antibodies to detect tumor lesions in a pilot radioimmunolocalization study, as well as to evaluate the kinetics, toxicity, and efficacy of i.p. administered 90Y-DOTA-labeled murine monoclonal antibody in a Phase I/II clinical trial of advanced ovarian cancer.

Tumour localisation with a radioactively labelled reshaped human monoclonal antibody.

A genetically reshaped human IgG1 monoclonal antibody (Hu2PLAP) with anti-tumour specificity, was radiolabelled with Indium-111 by chelation with a new macrocyclic compound (DOTA) which allows the production of stable radioimmunoconjugates for in vivo application. This was used to image seven patients with malignant disease, of whom two had been previously exposed to mouse monoclonal antibodies and had developed human anti-mouse antibodies (HAMA). Successful tumour localisation was seen in the four patients with active disease and antigen positive tumours.

Quantitative measurement of monoclonal antibody distribution and blood flow using positron emission tomography and 124iodine in patients with breast cancer.

The uptake and in vivo quantitation of monoclonal antibodies (MAbs) has been measured non-invasively using positron emission tomography (PET) and 124iodine in 9 patients with breast ductal carcinoma. Blood-flow measurements were also made using 15oxygen-labelled water and PET to evaluate antibody delivery; 7 patients were studied with HMFGI antibody and 2 patients with a non-specific antibody. Tumour uptake ranged from 2-7.

Intraperitoneal yttrium-90-labeled monoclonal antibody in ovarian cancer.

From March 1987 to March 1988, a phase I to II study was carried out in 25 patients with ovarian cancer. They received escalating doses of intraperitoneally (IP) administered yttrium-90 (Y-90)-labeled monoclonal antibody, HMFG1, against a tumor cell-surface antigen. Myelosuppression prevented an escalation of the administered Y-90 activity above 25 mCi.

Imaging of tumor in patients with indium-111-labeled biotin and streptavidin-conjugated antibodies: preliminary communication.

Tumor localization in patients has been achieved through the in vivo use of streptavidin and biotin. In these preliminary studies, the monoclonal antibody HMFG1 was conjugated with streptavidin and 1 mg was administered intravenously to each of 10 patients with documented squamous cell carcinoma of the lung. Two to 3 days later, 111In-labeled biotin was also administered intravenously.

Immunolocalisation of testicular tumours using radiolabelled monoclonal antibody to placental alkaline phosphatase.

Tumour associated monoclonal antibody against placental alkaline phosphatase (H17E2) was radiolabelled with Indium-111 and Iodine-123 and administered intravenously in 33 patients with primary and/or metastatic testicular tumour, as well as in 8 patients who were in complete remission after surgical excision of the tumour. The presence of a tumour was confirmed and correlated well with conventional diagnostic techniques and, in addition, the antibody scan revealed the presence of active disease in 2 patients with negative conventional imaging and with elevated serum markers. In addition, in one patient the CT produced a false positive result where the antibody scan was negative.

Preparation and in vivo study of 124I-labelled monoclonal antibody H17E2 in a human tumour xenograft model. A prelude to positron emission tomography (PET).

Positron emission tomography (PET) is a powerful nuclear medicine technique which, unlike conventional gamma camera tomography, relies on the coincidental detection of the two 511 keV gamma photons produced from the annihilation of a single positron. Hence good spatial resolution and accurate quantitation may be achieved. 124I (t1/2 = 4 days), a positron-emitting isotope of iodine, was chosen for our initial PET studies because the techniques of antibody radio-iodination are well established.

Intraperitoneally administered 90Y-labelled monoclonal antibodies as a third line of treatment in ovarian cancer. A phase 1-2 trial: problems encountered and possible solutions.

A phase 1-2 trial of 90Y-labelled monoclonal antibody, HMFG1 administered intraperitoneally to 30 patients with ovarian carcinoma is presented. The problems encountered with myelotoxicity are described, and the steps which have so far been taken to overcome this and to increase the dose of 90Y to an estimated tumouricidal level. Bone deposition of free 90Y limits the dose which can be administered without severe bone marrow toxicity.