Intraoperative Flow Cytometry for the Rapid Diagnosis and Validation of Surgical Clearance of Non-Melanoma Skin Cancer: A Prospective Clinical Feasibility Study.

Non-melanoma skin cancer (NMSC) is the most prevalent cancer in humans, with a high global incidence. We present a prospective clinical feasibility study on the use of intraoperative flow cytometry (iFC) for the instant diagnosis of NMSC and its complete surgical clearance. Flow cytometry, a laser-based technique, quantifies cell features, which has applications in cancer research. This study aim is to explore the potential applicability of iFC in detecting and characterizing NMSC and its surgical margins. In total, 30 patients who underwent diagnosis for NMSC were recruited. The method demonstrated high sensitivity (95.2%) and specificity (87.1%), with an accuracy of 91.1%, as confirmed with a receiver operating characteristic curve analysis. The results also indicated that most tumors were diploid, with two cases being hypoploid. The average G0/G1 fractions for normal and tumor tissue samples were 96.03 ± 0.30% and 88.03 ± 1.29%, respectively, with the tumor index escalating from 3.89 ± 0.30% to 11.95 ± 1.29% in cancerous cells. These findings underscore iFC's capability for precise intraoperative NMSC characterization and margin evaluation, promising enhanced complete tumor excision rates. Given the technique's successful application in various other malignancies, its implementation in NMSC diagnosis and treatment holds significant promise and warrants further research in clinical trials.

Towards non-invasive monitoring of non-melanoma skin cancer using spatially offset Raman spectroscopy.

BCC (basal cell carcinoma) and SCC (squamous cell carcinoma) account for the vast majority of cases of non-melanoma skin cancer (NMSC). The gold standard for the diagnosis remains biopsy, which, however, is an invasive and time-consuming procedure. In this study, we employed spatially offset Raman spectroscopy (SORS), a non-invasive approach, allowing the assessment of deeper skin tissue levels and collection of Raman photons with a bias towards the different layers of epidermis, where the non-melanoma cancers are initially formed and expand. Ex vivo Raman measurements were acquired from 22 skin biopsies using conventional back-scattering and a defocused modality (with and without a spatial offset). The spectral data were assessed against corresponding histopathological data to determine potential prognostic factors for lesion detection. The results revealed a positive correlation of protein and lipid content with the SCC and BCC types, respectively. By further correlating with patient data, multiple factor analysis (MFA) demonstrated a strong clustering of variables based on sex and age in all modalities. Specifically for the defocused modality (zero and 2 mm offset), further clustering occurred based on pathology. This study demonstrates the utility of the SORS technology in NMSC diagnosis prior to histopathological examination on the same tissue.

Pleomorphic dermal sarcoma: it might be rare but it exists.

Pleomorphic dermal sarcoma (PDS) is a rare mesenchymal tissue tumor. Its differential diagnosis from similar tumors, such as low differentiated squamous cell carcinoma, fibrosarcoma, desmoplastic melanoma, atypical fibroxanthoma (AFX), may be difficult, as they have similar clinical and histological presentation. We present a case of an 83-year-old man exhibiting an exophytic scalp lesion. Excision of the lesion was performed, ensuring clear surgical margins and pathologic examination revealed an invasive pleomorphic dermal sarcoma. This case highlights a rare case of a large pleomorphic dermal sarcoma, and it discusses the histological, molecular features, its differential diagnosis and management of PDS.

Circulating Tumor DNA in the Management of Early-Stage Breast Cancer.

Liquid biopsies refer to the isolation and analysis of tumor-derived biological material from body fluids, most commonly blood, in order to provide clinically valuable information for the management of cancer patients. Their non-invasive nature allows to overcome the limitations of tissue biopsy and complement the latter in guiding therapeutic decision-making. In the past years, several studies have demonstrated that circulating tumor DNA (ctDNA) detection can be used in the clinical setting to improve patient prognosis and monitor therapy response, especially in metastatic cancers. With the advent of significant technological advances in assay development, ctDNA can now be accurately and reliably identified in early-stage cancers despite its low levels in the bloodstream. In this review, we discuss the most important studies that highlight the potential clinical utility of ctDNA in early-stage breast cancer focusing on early diagnosis, detection of minimal residual disease and prediction of metastatic relapse. We also offer a concise description of the most sensitive techniques that are deemed appropriate for ctDNA detection in early-stage cancer and we examine their advantages and disadvantages, as they have been employed in various studies. Finally, we discuss future perspectives on how ctDNA could be better integrated into the everyday oncology practice.

TAMs and PD-1 Networking in Gastric Cancer: A Review of the Literature.

BACKGROUND: Gastric cancer (GC) is one of the most common and aggressive types of cancer. Immune checkpoint inhibitors (ICIs) have proven effective in treating various types of cancer. The use of ICIs in GC patients is currently an area of ongoing research. The tumor microenvironment (TME) also seems to play a crucial role in cancer progression. Tumor-associated macrophages (TAMs) are the most abundant population in the TME. TAMs are capable of displaying programmed cell death protein 1 (PD-1) on their surface and can form a ligand with programmed death ligand 1 (PD-L1), which is found on the surface of cancer cells. Therefore, it is expected that TAMs may significantly influence the immune response related to immune checkpoint inhibitors (ICIs). AIM OF THE STUDY: Understanding the role of TAMs and PD-1/PD-L1 networking in GC. METHODS: A systematic review of published data was performed using MEDLINE (PubMed), Embase, and Cochrane databases. We retrieved articles investigating the co-existence of TAMs and PD-1 in GC and the prognosis of patients expressing high levels of PD-1+ TAMs. RESULTS: Ten articles with a total of 2277 patients were included in the systematic review. The examined data suggest that the expression of PD-L1 has a positive correlation with the infiltration of TAMs and that patients who express high levels of PD-1+ TAMs may have a worse prognosis than those who express low levels of PD-1+ TAMs. CONCLUSIONS: TAMs play a pivotal role in the regulation of PD-1/PD-L1 networking and the progression of GC cells. Nevertheless, additional studies are needed to better define the role of TAMs and PD-1/PD-L1 networking in GC.

Flagellate dermatitis in a patient with testicular germ cell neoplasia on bleomycin.

Bleomycin, an antineoplastic antibiotic that inhibits DNA synthesis, is used to treat various malignant tumors such as Hodgkin's lymphoma, squamous cell carcinoma, and germ cell tumors. Flagellate erythema is a rare rash with a linear pattern that has been observed in association with bleomycin treatment. Herein, we present a 43-year-old patient with metastatic testicular cell neoplasms who developed a whiplash rash during treatment with a chemotherapy regimen that included bleomycin. A typical case of bleomycin-related flagellate dermatitis has been diagnosed and the main features of this characteristic adverse drug event are briefly discussed.

Eccrine Porocarcinoma of the Face is a Great Imitator With Aggressive Behavior.

Introduction: Eccrine porocarcinoma (EPC) is a rare subtype of non-melanoma skin cancer developing in the intraepithelial portion of eccrine sweat glands. It is branded with a highly metastatic potential and increased rate of local recurrence after treatment. EPC showcased a trend of developing on the extremities, with presentation on the face sparse. Objectives: Aim of the study was to evaluate the frequency, clinical features, and course of this malignancy presented on the face. Methods: A retrospective review of the skin cancers excised between January 2010 and June 2021 was conducted in the plastic surgery department of a tertiary hospital. Patients were included in the study if EPC on the face was histologically confirmed. A prospectively maintained clinic database and the pathological reports were used to collect data. Results: 4 EPC cases on the face out of 3984 confirmed skin cancers were identified. None of the cases was suspected clinically, but the diagnosis was established following the histopathologic examination. An aggressive postoperative behavior was confirmed in 2 cases. Conclusions: The variance in the clinical presentation and the non-specific characteristics are perplexing clinical diagnosis, with the histopathologic examination representing the current standard for confirmation. Early diagnosis and adequate surgical resection are recommended as treatment cornerstones. Clinical awareness ought to be raised and a definitive treatment protocol be established for optimized results.

Expression of orexin-A (hypocretin-A) in the hypothalamus after traumatic brain injury: A postmortem evaluation.

Traumatic brain injury (TBI) is one of the leading causes of mortality and morbidity. The key component of TBI pathophysiology is traumatic axonal injury (TAI), commonly referred to as diffuse axonal injury (DAI). Coma is a serious complication which can occur following traumatic brain injury (TBI). Recently, studies have shown that the central orexinergic/ hypocretinergic system exhibit prominent arousal promoting actions. Therefore, the purpose of this study is to investigate by immunohistochemistry the expression of beta-amyloid precursor protein (ß-APP) in white matter of parasagittal region, corpus callosum and brainstem and the expression of orexin-A (ORXA) in the hypothalamus after traumatic brain injury. RESULTS: DAI was found in 26 (53.06%) cases, assessed with ß-APP immunohistochemical staining in parasagittal white matter, corpus callosum and brainstem. Orexin-A immunoreactivity in hypothalamus was completely absent in 5 (10.2%) of the cases; moderate reduction of ORXA was observed in 9 (18.4%) of the cases; and severe reduction was observed in 7 (14.3%) of the cases. A statistically significant correlation was found between ß-APP immunostaining in white matter, corpus callosum and brainstem in relation to survival time (p < 0.002, p < 0.003 and p < 0.005 respectively). A statistically positive correlation was noted between ORX-A immunoreactivity in hypothalamus to survival time (p < 0.003). An inverse correlation was noted between the expression of ß-APP in the regions of brain studied to the expression of ORX-A in the hypothalamus of the cases studied (p < 0.005). CONCLUSIONS: The present study demonstrated by immunohistochemistry that reduction of orexin-A neurons in the hypothalamus, involved in coma status and arousal, enhanced the immunoexpression of ß-APP in parasagital white matter, corpus callosum and brainstem.

Antitumor Potential of Lippia citriodora Essential Oil in Breast Tumor-Bearing Mice.

Lippia citriodora is a flowering plant cultivated for its lemon-scented leaves and used in folk medicine for the preparation of tea for the alleviation of symptoms of gastrointestinal disorders, cold, and asthma. The oil extracted from the plant leaves was shown to possess antioxidant potential and to exert antiproliferative activity against breast cancer. The aim of this study was to further investigate potential antitumor effects of L. citriodora oil (LCO) on breast cancer. The in vitro antiproliferative activity of LCO was examined against murine DA3 breast cancer cells by the sulforhodamine B assay. We further explored the LCO's pro-apoptotic potential with the Annexin-PI method. The LCO's anti-migratory effect was assessed by the wound-healing assay. LCO was found to inhibit the growth of DA3 cells in vitro, attenuate their migration, and induce apoptosis. Finally, oral administration of LCO for 14 days in mice inhibited by 55% the size of developing tumors in the DA3 murine tumor model. Noteworthy, in the tumor tissue of LCO-treated mice the apoptotic marker cleaved caspase-3 was elevated, while a reduced protein expression of survivin was observed. These results indicate that LCO, as a source of bioactive compounds, has a very interesting nutraceutical potential.

Unusual abscess masquerading as poorly differentiated adenocarcinoma of the colon showing characteristics of choriocarcinoma.

Extragonadal non-gestational choriocarcinoma (ENC) is an uncommon malignant tumor occasionally found in the gastrointestinal tract. ENC is characterized by a biphasic tumor growth with distinct areas of adenocarcinoma and choriocarcinoma differentiation. Primary choriocarcinoma of the colon is extremely rare, with only 21 cases reported in the literature. Most of the perforation of colorectal cancers occurs in the abdominal cavity, while abdominal wall abscess is rare; the psoas abscess associated with colon carcinoma is even less observed. Herein, we report the case of a 61-year-old female with poorly differentiated adenocarcinoma of the ascending colon and sigmoid, with choriocarcinomatous differentiation, masquerading a psoas abscess formation. Unfortunately, despite the aggressive therapy, the patient's disease rapidly progressed, and she died within 2 months after the diagnosis. The typical morphological pattern, immunohistochemistry, and its correlation with serum ß-human chorionic gonadotropin enabled a correct diagnosis.

Immune Responses Raised in an Experimental Colon Carcinoma Model Following Oral Administration of Lactobacillus casei.

The role of dietary probiotic strains on host anticancer immune responses against experimental colon carcinoma was investigated. We have previously shown that Lactobacillus casei administration led to tumor growth suppression in an experimental colon cancer model. Here, we investigated the underlying immune mechanisms involved in this tumorgrowth inhibitory effect. BALB/c mice received daily live lactobacilli per os prior to the establishment of a syngeneic subcutaneous CT26 tumor. Tumor volume, cytokine production, T cell differentiation and migration, as well as tumor cell apoptosis were examined to outline potential immunomodulatory effects following L. casei oral intake. Probiotic administration in mice resulted in a significant increase in interferon gamma (IFNγ), Granzyme B and chemokine production in the tumor tissue as well as enhanced CD8+ T cell infiltration, accompanied by a suppression of tumor growth. Cytotoxic activity against cancer cells was enhanced in probioticfed compared to control mice, as evidenced by the elevation of apoptotic markers, such as cleaved caspase 3 and poly (ADPribose) polymerase 1 (PARP1), in tumor tissue. Oral administration of Lactobacillus casei induced potent Th1 immune responses and cytotoxic T cell infiltration in the tumor tissue of tumorbearing mice, resulting in tumor growth inhibition. Thus, the microorganism may hold promise as a novel dietary immunoadjuvant in raising protective anticancer immune responses.

Unusual abscess masquerading as poorly differentiated adenocarcinoma of the colon showing characteristics of choriocarcinoma

Extragonadal non-gestational choriocarcinoma (ENC) is an uncommon malignant tumor occasionally found in the gastrointestinal tract. ENC is characterized by a biphasic tumor growth with distinct areas of adenocarcinoma and choriocarcinoma differentiation. Primary choriocarcinoma of the colon is extremely rare, with only 21 cases reported in the literature. Most of the perforation of colorectal cancers occurs in the abdominal cavity, while abdominal wall abscess is rare; the psoas abscess associated with colon carcinoma is even less observed. Herein, we report the case of a 61-year-old female with poorly differentiated adenocarcinoma of the ascending colon and sigmoid, with choriocarcinomatous differentiation, masquerading a psoas abscess formation. Unfortunately, despite the aggressive therapy, the patient's disease rapidly progressed, and she died within 2 months after the diagnosis. The typical morphological pattern, immunohistochemistry, and its correlation with serum β-human chorionic gonadotropin enabled a correct diagnosis.

Effects of the Essential Oil from Pistacia lentiscus Var. chia on the Lateral Line System and the Gene Expression Profile of Zebrafish (Danio rerio).

Mastic essential oil exhibits anti-bacterial, anti-inflammatory, and anti-oxidant properties. With the growing interest of the use of mastic oil in the food and pharmaceutical industry, systematic in vivo studies are needed to address controlled usage and safety issues. In the present work we evaluated the safety of mastic oil using as a model the zebrafish lateral line system. In addition, we studied the gene expression profile of zebrafish fed with mastic oil-supplemented diet using microarray analysis. Our results showed that the hair cells of lateral line neuromasts are functional upon exposure of zebrafish larvae up to 20 ppm of mastic essential oil, while treatment with higher concentrations, 100 and 200 ppm, resulted in increased larvae mortality. Dietary supplementation of zebrafish with mastic essential oil led to differential expression of interferon response-related genes as well as the immune responsive gene 1 (irg1) that links cellular metabolism with immune defense. Notably, mucin 5.2, a constituent of the mucus hydrogel that protects the host against invading pathogens, was up-regulated. Our in vivo work provides information concerning the safety of mastic essential oil use and suggests dietary effects on gene expression related with the physical and immunochemical properties of the gastrointestinal system.

Thyroid Gland as a Target of Secondary Malignancies - an Autopsy Study and Review Data.

AIM: Secondary malignancies of the thyroid gland are rarely diagnosed but their incidence at autopsy is not uncommon. MATERIALS AND METHODS: To investigate the clinicopathological features of patients with metastatic tumours of the thyroid gland, we reviewed autopsy records and pathological features of 36 cases with thyroidal secondary tumours from 266 cases of malignant neoplasias (excluding cases of primary thyroid cancer), over a 16-year period. RESULTS: There were 19 men and 17 women in the study, ranging in age from 37 to 95 years (mean 70.4 years). The incidence of metastasis in thyroid gland was 0.9% in all autopsy cases, and 13.53% of the malignant tumours. The majority were carcinomas of epithelial origin. The lung was the most common primary tumour site (33.3%), followed by the breast (8.33%) and the kidney (8.33%). The most common non-epithelial malignancy was lymphoma, followed by leukaemia (total of both 25%). As for the microscopic morphological observations, diffuse infiltration pattern of tumour cells was noted in 63.89% of the cases, the formation of nodules in 33.33% of the cases and contiguous invasion in 2.79% of the cases. There were 35.71% cases of metastases associated with multinodular goitre and 28.57% cases associated with papillary microcarcinoma. CONCLUSION: Our study indicates that thyroid secondary malignancies are not infrequent and may constitute a diagnostic problem. Lung cancer is the most common neoplasm that metastasizes to the thyroid gland in north-western Greek population.

Hyperthermia Suppresses Post - In Vitro Proliferation and Tumor Growth in Murine Malignant Melanoma and Colon Carcinoma.

BACKGROUND: Several studies have highlighted hyperthermia's ability to enhance the effectiveness of radiation and chemotherapy in various in vitro and in vivo cancer models. MATERIALS AND METHODS: In vivo murine models of malignant melanoma and colon carcinoma were utilized for demonstrating hyperthermia's therapeutic effectiveness by examining levels of caspase 3, COX-2 and phospho-H2A.X (Ser139) as endpoints of apoptosis, proliferation and DNA damage respectively. RESULTS: Hyperthermia induced in vitro cytotoxicity in malignant melanoma (B16-F10) and colon carcinoma (CT26) cell lines. In addition, it reduced post-in vitro proliferation and suppression of tumor growth by inducing the expression of caspase-3 and phospho-H2A.X (Ser139) while reducing the expression of COX-2 in both murine cancer models. CONCLUSION: Hyperthermia can exert therapeutic effectiveness against melanoma and colon carcinoma by inhibiting a number of critical cellular cascades including apoptosis, proliferation and DNA damage.

Improving the Subcutaneous Mouse Tumor Model by Effective Manipulation of Magnetic Nanoparticles-Treated Implanted Cancer Cells.

Murine tumor models have played a fundamental role in the development of novel therapeutic interventions and are currently widely used in translational research. Specifically, strategies that aim at reducing inter-animal variability of tumor size in transplantable mouse tumor models are of particular importance. In our approach, we used magnetic nanoparticles to label and manipulate colon cancer cells for the improvement of the standard syngeneic subcutaneous mouse tumor model. Following subcutaneous injection on the scruff of the neck, magnetically-tagged implanted cancer cells were manipulated by applying an external magnetic field towards localized tumor formation. Our data provide evidence that this approach can facilitate the formation of localized tumors of similar shape, reducing thereby the tumor size's variability. For validating the proof-of-principle, a low-dose of 5-FU was administered in small animal groups as a representative anticancer therapy. Under these experimental conditions, the 5-FU-induced tumor growth inhibition was statistically significant only after the implementation of the proposed method. The presented approach is a promising strategy for studying accurately therapeutic interventions in subcutaneous experimental solid tumor models allowing for the detection of statistically significant differences between smaller experimental groups.

Dietary mastic oil extracted from Pistacia lentiscus var. chia suppresses tumor growth in experimental colon cancer models.

Plant-derived bioactive compounds attract considerable interest as potential chemopreventive anticancer agents. We analyzed the volatile dietary phytochemicals (terpenes) present in mastic oil extracted from the resin of Pistacia lentiscus var. chia and comparatively investigated their effects on colon carcinoma proliferation, a) in vitro against colon cancer cell lines and b) in vivo on tumor growth in mice following oral administration. Mastic oil inhibited - more effectively than its major constituents- proliferation of colon cancer cells in vitro, attenuated migration and downregulated transcriptional expression of survivin (BIRC5a). When administered orally, mastic oil inhibited the growth of colon carcinoma tumors in mice. A reduced expression of Ki-67 and survivin in tumor tissues accompanied the observed effects. Notably, only mastic oil -which is comprised of 67.7% α-pinene and 18.8% myrcene- induced a statistically significant anti-tumor effect in mice but not α-pinene, myrcene or a combination thereof. Thus, mastic oil, as a combination of terpenes, exerts growth inhibitory effects against colon carcinoma, suggesting a nutraceutical potential in the fight against colon cancer. To our knowledge, this is the first report showing that orally administered mastic oil induces tumor-suppressing effects against experimental colon cancer.

Genetic and epigenetic alterations in meningiomas.

Meningiomas originate from the arachnoid layer of the meninges and divided histologically into three grades: benign (grade I), atypical (grade II), and malignant meningiomas (grade III). Genetic alterations in grade I meningiomas include frequent deletions of chromosomal locus 22q12 and NF2 gene mutations and uncommon somatic SMARCB1 and SMARCE1gene mutations; In grade II meningiomas, chromosomal losses occur on 1p, 22q, 14q, 18q, 10, and 6q, and gains on 20q, 12q, 15q, 1q, 9q, and 17q; In grade III meningiomas, losses have been recognized on 6q, 10, and 14q and alterations of PTEN, CDKN2A and CDKN2B genes. Epigenetic alterations in meningiomas include hypermethylation of the tumor suppressor genes p73 in grade I meningiomas and TIMP3 GSTP1, MEG3, HOXA6, HOXA9, PENK, WNK2 and UPK3A genes with an increasing frequency according to grade. Abnormal expression of IGF signaling family genes and Wnt signaling pathway is associated with meningioma progression. MiRNA expression profiling of meningiomas show downregulation of miR-29c-3p, miR-200a, miR-145 and miR- 219-5p and upregulation of miR-21 miR-335 and miR-190a levels. In conclusion, extensive genetic and epigenetic alterations exist in meningiomas that may help assessing prognosis. In addition, since miRNA expression may be modified by artificial miRNAs, new effective therapeutic strategies may be developed especially for resistant or high grade meningiomas.

IFNs-signaling effects on lung cancer: an up-to-date pathways-specific review.

IFNs have found important applications in clinical medicine, including the treatment of lung malignancies. The biological effect of the IFN-receptor signaling is regulated essentially by three factors: the expression profile of the IFN itself, the profile of the receptor, and the expression of target genes. IFNs initiate their signaling by binding to specific receptors. The activated IFNs can directly induce gene transcription and/or multiple downstream signaling that both induce diverse cellular responses including the cell cycle arrest and the apoptosis in tumor cells. We provided evidence that IFN-γ enhances the pro cell death effects of Fas/CD95 in human neoplastic alveolar epithelial cell line, A549. We also found that p27 protein plays a pivotal role in the inducing cell death of IFNγ-CH-11-treated A549 cells, since it is involved in the Ras/Raf signaling pathway. This article discusses recent insights into these possible additional functions of IFNs in lung cancer treatment.