Medullary Thyroid Carcinoma: Recent Updates on the Diagnosis and Management

Medullary thyroid carcinoma is a hormone-producing malignant tumor that synthesizes calcitonin. MTC can be sporadic or familial. It has a malignant behavior. Our chapter has 3 parts: 1.Updates on the diagnosis of MTC -in this part we review the clinical findings in MTC: isolated thyroid nodule, palpable cervical lymph nodes and systemic manifestations. Fine needle aspiration, serum calcitonin, computed tomography (CT) and fludeoxyglucose - positron emission tomograpyh (FDG-PET) are summarized. Biomarkers with prognostic value are be described in detail: plasma calcitonin, carcino-embryonic antigen, germ-line RET mutation and matrix metalloproteinase. 2. Updates on the management and treatment of MTC -we discuss the surgical treatment, radiation therapy, systemic therapy with angiogenesis inhibitors and transcatheter arterial embolization to prevent extension of the tumor. Based on the characteristics of MTC a new approach using gene therapy has been developed to obtain complete remission of the carcinoma. 3. We describe a typical case of MTC from the oncology department, with cervical lymph nodes and a thyroid nodule. Immunohistochemistry staining showed calcitonin in the tumor cells. Thyroid ultrasound with fine needle aspiration biopsy confirmed the MTC. CT images of the cervical lymph nodes and thyroid nodule as well as microscopy images are presented. Chemotherapy with Dacarbazine was initiated with favorable outcome

Molecular basis and therapeutic targets in prostate cancer: A comprehensive review

Prostate cancer is one of the most significant causes of morbidity and mortality in male patients. The incidence increases with age, and it is higher among African Americans. The occurrence of prostate cancer is associated with many risk factors, including genetic and hereditary predisposition. The most common genetic syndromes associated with prostate cancer risk are BRCA-associated hereditary breast and ovarian cancer (HBOC) and Lynch syndrome. Local-regional therapy, i.e., surgery is beneficial in early-stage prostate cancer management. Advanced and metastatic prostate cancers require systemic therapies, including hormonal inhibition, chemotherapy, and targeted agents. Most prostate cancers can be treated by targeting the androgen-receptor pathway and decreasing androgen production or binding to androgen receptors (AR). Castration-resistant prostate cancer (CRPC) usually involves the PI3K/AKT/mTOR pathway and requires targeted therapy. Specific molecular therapy can target mutated cell lines in which DNA defect repair is altered, caused by mutations of BRCA2, partner and localizer of BRCA2 (PALB2), and phosphatase and tensin homolog (PTEN) or the transmembrane protease serine 2-ERG (TMPRSS2-ERG) fusion. Most benefits were demonstrated in cyclin dependent-kinase 12 (CDK12) mutated cell lines when treated with anti-programmed cell death protein 1 (PD1) therapy. Therapies targeting p53 and AKT are the subject of ongoing clinical trials. Many genetic defects are listed as diagnostic, prognostic, and clinically actionable markers in prostate cancer. Androgen receptor splice variant 7 (AR-V7) is an important oncogenic driver and an early diagnostic and prognostic marker, as well as a therapeutic target in hormone-resistant CRPC. This review summarizes the pathophysiological mechanisms and available targeted therapies for prostate cancer

Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial

Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population

Stretching and Compression of Double Dusty Plasma Vortex

The interest in complex plasmas is increasing due to the multiple applications they target (astrophysics, plasma fusion, industry, etc.). A crystal with two vortexes made of spherical microparticles that levitates in an rf plasma interacts with a gas jet. The crystal is displaced in the jet propagation direction due to the neutral pushing force, maintaining its vortex structure. The crystal shift also involves a change of its shape, especially at the level of the two vortexes. One vortex is stretched, and the other one is compressed. During the three phases of modification of the shape of the crystal, its length is approximately constant, about 12.5 mm, this being a consequence of the fact that electric forces and ion drag forces are preserved. The orderly structure of the crystal lasts until the particles begin to fall on the bottom electrode. The changing of the vorticity in the crystal regions can be attributed to the neutral push force

Splitting CO₂ in Intense Pulsed Plasma Jets

The splitting of CO2 was studied in a pulsed plasma discharge produced in a coaxial gun at voltages between ~1 and 2 kV and peak discharge currents of 7 to 14 kA. The plasma was ejected from the gun at a speed of a few km/s and had electron temperatures between 11 and 14 eV with peak electron densities ~2.4 × 1021 particles m−3. Spectroscopic measurements were carried out in the plasma plume produced at pressures between 1 and 5 Torr, and evidence of CO2 dissociation into oxygen and CO was found. An increased discharge current led to the observation of more intense spectra lines and the presence of new oxygen lines, which implies more dissociation channels. Several dissociation mechanisms are discussed, the main candidate being the splitting of the molecule by direct electron impact. Estimates of dissociation rates are made based on measured plasma parameters and interaction cross-sections available in the literature. A possible application of this technique is in future Mars missions where the coaxial plasma gun running in the atmosphere could be able to produce oxygen at a rate of the order of over 100 g per hour in a highly repetitive regime

IoT solution for monitoring indoor climate parameters in open space offices

Although there are numerous high performance BMS (Building Management System), which monitor the indoor climate parameters, data access, sensor positioning, and other aspects may not be under control. On the other hand, IoT (Internet of Things) is experiencing exponential growth, as more and more devices and sensors are connected to the cloud. Thus, a sensor monitoring solution for indoor climate parameters was developed. The proposed solution is not expensive, and it is based on a Raspberry Pi board endowed with temperature, humidity, and pressure sensors. The developed application reads the values detected by the sensors, processes the date, and afterwards transmit the information to the IoT ThingSpeak platform. The large area is characteristic of open space offices, so the influence of radiant walls is small, and the operative temperature can be approximate with air temperature. This type of building is conditioned by the air conditioning system, so the air speed in this indoor environment is usually low and could be approximated by the design. So, with the data read by the developed solution the thermal comfort parameters can be approximated. If inadequate values are found, teams that carry out complex and precise measurements could be sent to the site. To achieve this goal a PMV calculator software is developed. Its validity is tested in accordance with the European standard ISO 7730. After that, the PMV computer is used with data read from sensors. Both the data read from the sensors and the newly calculated PMV are sent to the ThingSpeak IoT platform

Synthesis and Bioinformatic Characterization of New Schiff Bases with Possible Applicability in Brain Disorders

(1) Background: The research aims to find new treatments for neurodegenerative diseases, in particular, Alzheimer’s disease. (2) Methods: This article presents a bioinformatics and pathology study of new Schiff bases, (EZ)-N′-benzylidene-(2RS)-2-(6-chloro-9H-carbazol-2-yl)propanehydrazide derivatives, and aims to evaluate the drug-like, pharmacokinetic, pharmacodynamic and pharmacogenomic properties, as well as to predict the binding to therapeutic targets by applying bioinformatics, cheminformatics and computational pharmacological methods. (3) Results: We obtained these Schiff bases by condensing (2RS)-2-(6-chloro-9H-carbazol-2-yl)propanehydrazide with aromatic aldehydes, using the advantages of microwave irradiation. The newly synthesized compounds were characterized spectrally, using FT-IR and NMR spectroscopy, which confirmed their structure. Using bioinformatics tools, we noticed that all new compounds are drug-likeness features and may be proposed as potentially neuropsychiatric drugs (4) Conclusions: Using bioinformatics tools, we determined that the new compound 1e had a high potential to be used as a good candidate in neurodegenerative disorders treatment

Low Blue Dose Photodynamic Therapy with Porphyrin-Iron Oxide Nanoparticles Complexes: In Vitro Study on Human Melanoma Cells

The purpose of this study was to investigate the effectiveness in photodynamic therapy of iron oxide nanoparticles (γ-Fe2O3 NPs), synthesized by laser pyrolysis technique, functionalized with 5,10,15,20-(Tetra-4-sulfonatophenyl) porphyrin tetraammonium (TPPS) on human cutaneous melanoma cells, after only 1 min blue light exposure. The efficiency of porphyrin loading on the iron oxide nanocarriers was estimated by using absorption and FTIR spectroscopy. The singlet oxygen yield was determined via transient characteristics of singlet oxygen phosphorescence at 1270 nm both for porphyrin functionalized nanoparticles and rose bengal used as standard. The irradiation was performed with a LED (405 nm, 1 mW/cm2) for 1 min after melanoma cells were treated with TPPS functionalized iron oxide nanoparticles (γ-Fe2O3 NPs_TPPS) and incubated for 24 h. Biological tests revealed a high anticancer effect of γ-Fe2O3 NPs_TPPS complexes indi-cated by the inhibition of tumor cell proliferation, reduction of cell adhesion, and induction of cell death through ROS generated by TPPS under light exposure. The biological assays were combined with the pharmacokinetic prediction of the porphyrin

Bemarituzumab as first-line treatment for locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma: final analysis of the randomized phase 2 FIGHT trial.

BACKGROUND: We report the final results of the randomized phase 2 FIGHT trial that evaluated bemarituzumab, a humanized monoclonal antibody selective for fibroblast growth factor receptor 2b (FGFR2b), plus mFOLFOX6 in patients with FGFR2b-positive (2 + /3 + membranous staining by immunohistochemistry), HER-2-negative gastric or gastroesophageal junction cancer (GC). METHODS: Patients received bemarituzumab (15 mg/kg) or placebo once every 2 weeks with an additional bemarituzumab (7.5 mg/kg) or placebo dose on cycle 1 day 8. All patients received mFOLFOX6. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, and safety. Efficacy was evaluated after a minimum follow-up of 24 months. RESULTS: In the bemarituzumab-mFOLFOX6 (N = 77) and placebo-mFOLFOX6 (N = 78) arms, respectively, 59.7% and 66.7% of patients were FGFR2b-positive in ≥ 10% of tumor cells. The median PFS (95% confidence interval [CI]) was 9.5 months (7.3-13.7) with bemarituzumab-mFOLFOX6 and 7.4 months (5.7-8.4) with placebo-mFOLFOX6 (hazard ratio [HR], 0.72; 95% CI 0.49-1.08); median OS (95% CI) was 19.2 (13.6-24.2) and 13.5 (9.3-15.9) months, respectively (HR 0.77; 95% CI 0.52-1.14). Observed efficacy in FGFR2b-positive GC in ≥ 10% of tumor cells was: PFS: HR 0.43 (95% CI 0.26-0.73); OS: HR 0.52 (95% CI 0.31-0.85). No new safety findings were reported. CONCLUSIONS: In FGFR2b-positive advanced GC, the combination of bemarituzumab-mFOLFOX6 led to numerically longer median PFS and OS compared with mFOLFOX6 alone. Efficacy was more pronounced with FGFR2b overexpression in ≥ 10% of tumor cells. Confirmatory phase 3 trials are ongoing (NCT05052801, NCT05111626). CLINICAL TRIAL REGISTRATION: NCT03694522