Highly selective behaviour of colon adenoma after administration of EMR composition and its HCT116-based model.

When applying the improved composition of the solution used during endoscopic mucosal resection (EMR), we observed unexpectedly large and quantitatively significant differences in adenoma response vs. healthy tissue of the surrounding GIT tract, namely, the selective reaction enhancing the adenoma volume and differentiated colour. The in vitro experiments on the model neoplasia cell line HCT116 suggest that the robust differences in the response of starving cells can be traced down principally to tetrastarch digestion and the enhanced metabolic rate of neoplastic cells. The neoplastic tissue grows into several intestine layers so that submucosal injection of iso-oncotic tetrastarch compound leads to degradation of starch and production of oncotic molecules in submucosa transported by facilitated transport into the neoplastic tissue. The colour distinction is due to concentration differences of the reporting dye between three separated compartments, further enhancing the utility of the contrasting mixture. The diffusion dynamics shall be tuneable by optimizing starch composition, improving desirable pharmacokinetics.

Nasal mucoepidermoid carcinoma after radiotherapy: Case report

Introduction Mucoepidermoid carcinoma (MEC) is a tumor originated from the epithelium of the glandular excretory ducts and has highly variable biological potential. It is the most prevalent cancer of the salivary glands. The present report aims to describe a case of nasal mucoepidermoid carcinoma that developed after adjuvant radiotherapy (RT) treatment of a recurrent pituitary macroadenoma. Case Report Male patient, 62 years old, presented with recurrent nasal epistaxis on the right, associated with intense pulsatile headache, visual analogical scale (VAS) 10/10, with improvement only with the use of opioids and morphine. After undergoing oncological screening and study by imaging exams, the presence of an expansive seal lesion with suprasellar extension was seen, involving the medial wall of the cavernous segment of the right carotid artery and the anterior cerebral artery, as well as the presence of a new expansive lesion in the right nasal cavity, with ethmoid bone invasion superiorly and medial orbit wall invasion laterally, compressing the ipsilateral optic nerve canal. Discussion Sinonasal neoplasms represent a small portion of all malignancies of the upper aerodigestive tract, accounting for < 5% of these neoplasms. The development of MEC involves risk factors such as occupational issues, history of trauma and surgery involving the nasal area, and radiation exposure, as in previous RT. Conclusion Mucoepidermoid carcinoma is an uncommon neoplasia and can be associated with RT treatment, as used in cases of recurrent pituitary macroadenoma. In general, surgical resection to obtain free margins of neoplastic tissue is the aimed treatment, seeking better prognosis.

Highly selective behaviour of colon adenoma after administration of EMR composition and its HCT116-based model.

When applying the improved composition of the solution used during endoscopic mucosal resection (EMR), we observed unexpectedly large and quantitatively significant differences in adenoma response vs. healthy tissue of the surrounding GIT tract, namely, the selective reaction enhancing the adenoma volume and differentiated colour. The in vitro experiments on the model neoplasia cell line HCT116 suggest that the robust differences in the response of starving cells can be traced down principally to tetrastarch digestion and the enhanced metabolic rate of neoplastic cells. The neoplastic tissue grows into several intestine layers so that submucosal injection of iso-oncotic tetrastarch compound leads to degradation of starch and production of oncotic molecules in submucosa transported by facilitated transport into the neoplastic tissue. The colour distinction is due to concentration differences of the reporting dye between three separated compartments, further enhancing the utility of the contrasting mixture. The diffusion dynamics shall be tuneable by optimizing starch composition, improving desirable pharmacokinetics.

Histopathologic and MR Imaging Appearance of Spontaneous and Radiation-Induced Necrosis in Uveal Melanomas: Initial Results

Necrosis in uveal melanomas can be spontaneous or induced by radiotherapy. The purpose of our study was to compare the histopathologic and MRI findings of radiation-induced necrosis of a group of proton beam-irradiated uveal melanomas with those of spontaneous necrosis of a control group of patients undergoing primary enucleation. 11 uveal melanomas who had undergone proton beam radiotherapy, MRI and secondary enucleation, and a control group of 15 untreated uveal melanomas who had undergone MRI and primary enucleation were retrospectively identified. Within the irradiated and nonirradiated group, 7 and 6 eyes with histological evidence of necrosis respectively, were furtherly selected for the final analysis; the appearance of necrosis was assessed at histopathologic examination and MRI. Irradiated melanomas showed a higher degree of necrosis as compared with nonirradiated tumors. Irradiated and nonirradiated lesions differed based on the appearance and distribution of necrosis. Irradiated tumors showed large necrotic foci, sharply demarcated from the viable neoplastic tissue; nonirradiated tumors demonstrated small, distinct foci of necrosis. Radiation-induced necrosis, more pigmented than surrounding viable tumor, displayed high signal intensity on T1-weighted and low signal intensity on T2-weighted images. The hemorrhagic/coagulative necrosis, more prevalent in nonirradiated tumors (4 out of 6 vs. 1 out of 7 cases), appeared hyperintense on T2-weighted and hypointense on T1-weighted images. Our study boosts the capability to recognize radiation-induced alterations in uveal melanomas at MRI and may improve the accuracy of radiologists in the evaluation of follow-up MR examination after radiotherapy.

Positive ROS (Reactive Oxygen Species) Modulator Engineered Device Support Skin Treatment in Locally Advanced Breast Cancer (LABC) Enhancing Patient Quality of Life

The development of research in genetic and biochemical fields has made it possible to investigate certain metabolic aspects of the microenvironment of chronic skin lesions, including altered cell signalling, highlighting its importance in determining the blockage of repair processes. The purpose of this prospective observational study is to evaluate the efficacy of a medical device consisting of a polyester scaffold enriched with an oleic matrix with controlled release of ROS in the management of LABC skin lesions. During the period from October 2018 to March 2020, 20 patients with locally advanced breast cancer were enrolled and ten were treated with the devices abovementioned. After 30 days of treatment all patients treated reported a general improvement in local conditions with reduction in ulceration area, exudate and odour. The results suggest that the application of these devices even in particular conditions (healthy and neoplastic tissue) does not lead to the onset of negative effects due to the release of ROS, though their role in tissue repair requires further study to fully understand their potential and increase the fields of application of the device by exploiting its modulation capabilities.

Paired 18F-Fluorodeoxyglucose (18F-FDG), and 64Cu-Copper(II)-diacetyl-bis(N(4)-methylthiosemicarbazone) (64Cu-ATSM) PET Scans in Dogs with Spontaneous Tumors and Evaluation for Hypoxia-Directed Therapy

Hypoxia is associated with neoplastic tissue, protecting cancer cells from death by irradiation and chemotherapy. Identification of hypoxic volume of tumors could optimize patient selection for hypoxia-directed medical, immunological, and radiation therapies. Clostridium novyi-NT (CNV-NT) is an oncolytic bacterium derived from attenuated wild-type Clostridium novyi spores, which germinates exclusively in the anaerobic core of tumors with low-oxygen content. The hypothesis was that 64Cu-ATSM would localize to regions of hypoxia, and that greater hypoxic volume would result in greater germination of Clostridium novyi-NT (CNV-NT). Tumor-bearing companion dogs were recruited to a veterinary clinical trial. Dogs received a CT scan, 18F-FDG PET scan (74 MBq) and 64Cu-ATSM PET scan (74 MBq). Scan regions of interest were defined as the highest 20% of counts/voxel for each PET scan, and regions with voxels overlapping between the two scans. Maximum standardized uptake value (MaxSUV) and threshold volume were calculated. Direct oximetry was performed in select tumors. Tumor types evaluated included nerve sheath tumor (10), apocrine carcinoma (1), melanoma (3) and oral sarcoma (6). MaxSUVATSM ranged from 0.3–6.6. Measured oxygen tension ranged from 0.05–89.9 mmHg. Inverse of MaxSUVATSM had a linear relationship with oxygen tension (R2 = 0.53, P = 0.0048). Hypoxia &lt;8 mmHg was associated with an SUVATSM &gt; 1.0. Hypoxic volume ranged from 0 to 100% of gross tumor volume (GTV) and MaxSUVATSM was positively correlated with hypoxic volume (R = 0.674; P = 0.0001), but not GTV (P = 0.182). Tumor hypoxic volume was heterogeneous in location and distribution. 64Cu-ATSM-avid regions were associated with differential CT attenuation. Hypoxic volume did not predict CNV-NT germination. 64Cu-ATSM PET scanning predicts hypoxia patterns within spontaneously occurring tumors of dogs as measured by direct oxymetry. Total tumor volume does not accurately predict degree or proportion of tumor hypoxia.

Comparison of Two Blood-Based Genotyping Tests to Investigate the KRAS G12C Mutation in Patients with Non-Small-Cell Lung Cancer at Failure of First-Line Treatments

Although molecular profiling at diagnosis has traditionally relied on direct sampling of neoplastic tissue, cancer clonal evolution represents a critical obstacle to use primary tissue biopsies to guide clinical decision-making at the time of progressive disease. Liquid biopsies might offer enormous advantages over tissue biopsies, tracking in real-time temporal-based tumor dynamics following each line of treatment. Here, we compared two liquid biopsy assays, specifically real-time polymerase chain reaction and next-generation sequencing, to track the KRAS G12C mutation at onset of progression from previous lines of therapy. The KRAS G12C mutation was acquired at the time of progressive disease in 24% of patients. Furthermore, all patients with KRAS G12C mutation-positive tissue became negative in ctDNA at progressive disease. The presence of other somatic mutations in all these samples confirmed the tumor origin of the circulating DNA. This pilot study suggests that in the assessment of the plasma KRAS G12C mutation as a druggable target, real-time PCR assay Idylla might be a suitable approach to better match patients to interventional biomarker-targeted therapies.

Dysregulation of Translation Factors EIF2S1, EIF5A and EIF6 in Intestinal-Type Adenocarcinoma (ITAC)

Intestinal-type adenocarcinoma (ITAC) is a rare cancer of the nasal cavity and paranasal sinuses that occurs sporadically or secondary to exposure to occupational hazards, such as wood dust and leather. Eukaryotic translation initiation factors have been described as promising targets for novel cancer treatments in many cancers, but hardly anything is known about these factors in ITAC. Here we performed in silico analyses, evaluated the protein levels of EIF2S1, EIF5A and EIF6 in tumour samples and non-neoplastic tissue controls obtained from 145 patients, and correlated these results with clinical outcome data, including tumour site, stage, adjuvant radiotherapy and survival. In silico analyses revealed significant upregulation of the translation factors EIF6 (ITGB4BP), EIF5, EIF2S1 and EIF2S2 (p < 0.05) with a higher arithmetic mean expression in ITAC compared to non-neoplastic tissue (NNT). Immunohistochemical analyses using antibodies against EIF2S1 and EIF6 confirmed a significantly different expression at the protein level (p < 0.05). In conclusion, this work identifies the eukaryotic translation initiation factors EIF2S1 and EIF6 to be significantly upregulated in ITAC. As these factors have been described as promising therapeutic targets in other cancers, this work identifies candidate therapeutic targets in this rare but often deadly cancer.

ACKR3 induces the perturbation of rRNA biogenesis: a novel mechanism of colorectal tumorigenesis

Atypical chemokine receptor 3 (ACKR3) has emerged as a key player in several biologic processes. However, much less is known the underlying mechanisms of ACKR3 in promoting tumorigenesis. We found, in human and animal model, that activation of ACKR3 promotes colorectal tumorigenesis through the NOLC1-induced perturbations of rRNA biogenesis. As compared with non-neoplastic tissue, human colonic cancer tissues demonstrated higher expression of ACKR3, and high ACKR3 expression was associated with increased severity of colonic cancer. Villin-ACKR3 transgenic mice demonstrated the characteristics of ACKR3-induced colorectal cancer, showing nuclear β-arrestin-1-activated perturbation of rRNA biogenesis. Activation of ACKR3 induced nuclear translocation of β-arrestin-1 (β-arr1), leading to the interaction of β-arr1 with nucleolar and coiled-body phosphoprotein 1 (NOLC1). As the highly phosphorylated protein in the nucleolus, NOLC1 further interacted with Fibrillarin, a highly conserved nucleolar methyltransferase responsible for ribosomal RNA methylation, leading to the increase of methylation in Histone H2A, resulting in the promotion of rRNA transcription of ribosome biogenesis. Conclusion: ACKR3 promotes colorectal tumorigenesis through the perturbation of rRNA biogenesis by nuclear β-arr1-induced interaction of NOLC1 with Fibrillarin.

Sebaceous Carcinoma of The Lip: Report of a Case and Literature Review.

Background Sebaceous carcinoma (SC) is a very rare, aggressive, malignant tumor arising in the adnexal epithelium of the sebaceous gland. SC in the oral cavity is extremely rare, in literature there are only 14 cases. We reported the 4th case of sebaceous carcinoma involving the lip Case presentation A 71-year-old male smoker presented an ulcerated lesion in the lateral region of the lower lip. The patient stated that the lesion had been present for 1 year. The past medical history was unremarkable. Extra-oral examination revealed a markedly ulcerated, exophytic, irregularly shaped, indurated mass of the lower right labial region, measuring 1.8 cm in size. The nodular lesion, located at the point of transition between mucosa and skin, showed a central ulceration. No other intraoral lesions were identified. The clinical differential diagnosis included squamous cell carcinoma, basal cell carcinoma with sebaceous differentiation and salivary gland neoplasms. The operation was performed under local anaesthesia. On histopathological examination, the tumor was composed by nodules or sheet of cells separated by a fibrovascolar stroma. The neoplastic tissue was deeply infiltrating, involving the submucosa and even the underlying muscle. Neoplastic cells showed a range of sebaceous differentiation with finely vacuolated rather than clear cytoplasm. Neoplastic cells were positive for S-100 protein, EMA, but negative for CEA. Therefore, based on these findings, a diagnosis of sebaceous carcinoma of the lower lip was rendered. Conclusion The histogenesis, differential diagnosis, and clinicopathologic conditions of this disease in the literature were reviewed. SC should be distinguished from other tumors full of vacuolated clear cells. Some useful biomarkers can be Ki-67, P53, CK, PAS, S-100, EMA, and AR.