Regulation of Apoptosis during Environmental Skin Tumor Initiation

Skin cancer is more prevalent than any other cancer in the United States. Nonmelanoma skin cancers are the more common forms of skin cancer that affect individuals. The development of squamous cell carcinoma, the second most common type of skin cancer, can be stimulated by exposure of environmental carcinogens, such as chemical toxicants or UVB. It is developed by three distinct stages: initiation, promotion, and progression. During the initiation, the fate of DNA-damaged skin cells is determined by the homeostatic regulation of pro-apoptotic and antiapoptotic signaling pathways. The imbalance or disruption of either signaling will lead to the survival of initiated cells, resulting in the development of skin cancer. In this chapter, we will discuss signaling pathways that regulate apoptosis and the impact of their dysfunction during skin tumor initiation

Regulation of Apoptosis during Environmental Skin Tumor Initiation

Skin cancer is more prevalent than any other cancer in the United States. Nonmelanoma skin cancers are the more common forms of skin cancer that affect individuals. The development of squamous cell carcinoma, the second most common type of skin cancer, can be stimulated by exposure of environmental carcinogens, such as chemical toxicants or UVB. It is developed by three distinct stages: initiation, promotion, and progression. During the initiation, the fate of DNA-damaged skin cells is determined by the homeostatic regulation of pro-apoptotic and antiapoptotic signaling pathways. The imbalance or disruption of either signaling will lead to the survival of initiated cells, resulting in the development of skin cancer. In this chapter, we will discuss signaling pathways that regulate apoptosis and the impact of their dysfunction during skin tumor initiation

Protein Tyrosine Phosphatases as Potential Regulators of STAT3 Signaling

The signal transducer and activator of transcription 3 (STAT3) protein is a major transcription factor involved in many cellular processes, such as cell growth and proliferation, differentiation, migration, and cell death or cell apoptosis. It is activated in response to a variety of extracellular stimuli including cytokines and growth factors. The aberrant activation of STAT3 contributes to several human diseases, particularly cancer. Consequently, STAT3-mediated signaling continues to be extensively studied in order to identify potential targets for the development of new and more effective clinical therapeutics. STAT3 activation can be regulated, either positively or negatively, by different posttranslational mechanisms including serine or tyrosine phosphorylation/dephosphorylation, acetylation, or demethylation. One of the major mechanisms that negatively regulates STAT3 activation is dephosphorylation of the tyrosine residue essential for its activation by protein tyrosine phosphatases (PTPs). There are seven PTPs that have been shown to dephosphorylate STAT3 and, thereby, regulate STAT3 signaling: PTP receptor-type D (PTPRD), PTP receptor-type T (PTPRT), PTP receptor-type K (PTPRK), Src homology region 2 (SH-2) domain-containing phosphatase 1(SHP1), SH-2 domain-containing phosphatase 2 (SHP2), MEG2/PTP non-receptor type 9 (PTPN9), and T-cell PTP (TC-PTP)/PTP non-receptor type 2 (PTPN2). These regulators have great potential as targets for the development of more effective therapies against human disease, including cancer

Toxicity Studies on Secretio Bufonis: A Traditional Supplement in Asia

AbstractObjectivesThis study was performed to investigate the toxicity of Secretio Bufonis (SB) on male mice and assess its no-observed-adverse-effect-level (NOAEL).Materials and MethodsAfter feeding an aqueous solution of SB extracts to mice for either 1 or 8 weeks, their blood and urine were assayed and their liver and kidney morphology examined. The numerical data was analyzed by the Mann-Whitney U-test and analysis of variance test.ResultsMice administered SB in 50 mg/kg/day for 1 week had higher heart weights and higher aspartate transaminase activities; those administered SB in 0.01 and 0.05 mg/kg/day for 8 weeks had lower creatinine concentrations; and those administered SB in 0.5 mg/kg/day for 8 weeks had higher brain weights and higher blood urea nitrogen.ConclusionsThe extracts of SB had cardiac toxicity in the short term and hepatotoxicity in the long term. The NOAEL of the extract was under 5 mg/kg/day for 1 week and under 0.25 mg/kg/day for 8 weeks

Regulation of Apoptosis during Environmental Skin Tumor Initiation

Skin cancer is more prevalent than any other cancer in the United States. Non-melanoma skin cancers are the more common forms of skin cancer that affect individuals. The development of squamous cell carcinoma, the second most common type of skin cancer, can be stimulated by exposure of environmental carcinogens, such as chemical toxicants or UVB. It is developed by three distinct stages: initiation, promotion, and progression. During the initiation, the fate of DNA-damaged skin cells is determined by the homeostatic regulation of pro-apoptotic and anti-apoptotic signaling pathways. The imbalance or disruption of either signaling will lead to the survival of initiated cells, resulting in the development of skin cancer. In this chapter, we will discuss signaling pathways that regulate apoptosis and the impact of their dysfunction during skin tumor initiation

Resection of individually identified high-rate high-frequency oscillations region is associated with favorable outcome in neocortical epilepsy

Objectives: High-frequency oscillations (HFOs) represent a novel electrophysiologic marker of endogenous epileptogenicity. Clinically, this propensity can be utilized to more accurately delineate the resection margin before epilepsy surgery. Currently, prospective application of HFOs is limited because of a lack of an exact quantitative measure to reliably identify HFO-generating areas necessary to include in the resection. Here, we evaluated the potential of a patient-individualized approach of identifying high-rate HFO regions to plan the neocortical resection. Methods: Fifteen patients with neocortical seizure-onset zones (SOZs) underwent intracranial electroencephalographic monitoring. To identify interictal HFOs, we applied an automated, hypersensitive HFO-detection algorithm followed by post hoc processing steps to reject false detections. The spatial relationship between HFO distribution and the SOZ was evaluated. To address high interpatient variability in HFO properties, we evaluated the high-rate HFO region, an unbiased statistical parameter, in each patient. The relationship between resection of the high-rate HFO region and postoperative outcome was examined. Results: Grouped data demonstrated that the rate of ripple (60–200 Hz) and fast ripple (200–500 Hz) was increased in the SOZ (both p < 0.01). Intrapatient analysis of the HFO distribution localized the SOZ in 11 patients. High-rate HFO regions were determined in all patients by an individually adjusted threshold. Resection of high-rate HFO regions was significantly associated with a seizure-free outcome (p < 0.01). The extent/ratio of SOZ or spiking region resection did not differ between seizure-free and seizure-persistent groups. Significance: Intrapatient analysis of high-rate HFOs provides more detailed description of HFO-generating areas and can mark the areas of clinically significant epileptogenicity—a crucial component of the neocortical epileptic network that should be removed to achieve a good outcome. Validating and adopting an unbiased quantitative HFO parameter has the potential to propel wider and prospective utilization of HFOs in the surgical treatment of neocortical epilepsy and to improve its outcome

Suggested Indications for Enucleation of Solid Pseudopapillary Neoplasms in Pediatric Patients

Background: Solid pseudopapillary neoplasms (SPNs) are rare, low-grade, malignant neoplasms that can occur in pediatric patients. Although complete resection of the tumor is the principle treatment, SPN enucleation (EN) has been reported to be effective in children. This study aimed to examine the feasibility and safety of EN by comparing it with conventional pancreatectomy (CP), and to present the indications for its use in pediatric patients.Methods: We retrospectively reviewed the medical records of 66 patients who underwent surgery for SPN at our institution from October 1992 to April 2018. Surgical methods, postoperative complications, hospital stay, and recurrence were compared.Results: Of the 66 patients, 15 (22.7%) were treated with EN and 51 (77.3%) were treated with CP. The mean duration of EN operation was 262 min (±145 min) and of CP was 345 min (±195 min). There was no statistically significant difference between the two methods (P = 0.13). To objectively compare the mass size between patients, we introduced a tumor size/intraperitoneal width ratio, which also revealed no significant difference between the 2 surgery groups (P = 0.21). The EN group had one case of recurrence at the resection site. The complications observed were fluid collection, splenic infarctions, hematomas, pancreatic fistulas, portal vein thromboses, and chylous drainage, among which pancreatic fistulas were the most frequent followed by moderate-severe fistulas in the EN group (P &lt; 0.001). The mean postoperative fasting time (EN 17.0 ± 8.7 days vs. CP 5.1 ± 3.3 days, P &lt; 0.001) and mean hospital stay (EN 23.4 ± 10.0 days vs. CP 13.2 ± 6.5 days, P = 0.002) showed statistically significant differences.Conclusion: Compared with CP treatment, EN of SPNs in children has the disadvantages of prolonged fasting times and hospital stays to recover from moderate pancreatic fistulas. However, if appropriate indications are applied, EN can be considered a safe and effective surgical procedure for children

Cystic Dysplasia of the Rete Testis Accompanying an Inguinal Hernia: A 63-Year-Old Man

Cystic dysplasia of the rete testis (CDT) is a very rare congenital benign testicular tumor that is often associated with ipsilateral genitourinary anomalies. It is usually found in the pediatric population and must be differentially diagnosed from a malignant lesion. Here we report the case of a 63-year-old man with a left inguinal hernia who visited our urologic outpatient clinic. Scrotal ultrasonography showed a left direct inguinal hernia in the inguinal area and a well-circumscribed cystic lesion containing multiple minute cysts with echogenic foci occupying almost one-third of the left testicular parenchyma. Testicular tumor markers were within the normal range and a computed tomography scan of the abdomen showed no genitourinary abnormalities. We presumed that the left testicular lesion was malignant, and the patient underwent radical orchiectomy. However, the pathologic examination revealed a CDT. Here we present this case of a 63-year-old man with an inguinal hernia accompanied by multiple cystic lesions on the left testis

Fargesin Inhibits EGF-Induced Cell Transformation and Colon Cancer Cell Growth by Suppression of CDK2/Cyclin E Signaling Pathway

Although the lignan compound fargesin is a major ingredient in Shin-Yi, the roles of fargesin in carcinogenesis and cancer cell growth have not been elucidated. In this study, we observed that fargesin inhibited cell proliferation and transformation by suppression of epidermal growth factor (EGF)-stimulated G1/S-phase cell cycle transition in premalignant JB6 Cl41 and HaCaT cells. Unexpectedly, we found that signaling pathway analyses showed different regulation patterns in which fargesin inhibited phosphatidylinositol 3-kinase/AKT signaling without an alteration of or increase in mitogen activated protein kinase (MAPK) in JB6 Cl41 and HaCaT cells, while both signaling pathways were abrogated by fargesin treatment in colon cancer cells. We further found that fargesin-induced colony growth inhibition of colon cancer cells was mediated by suppression of the cyclin dependent kinase 2 (CDK2)/cyclin E signaling axis by upregulation of p21WAF1/Cip1, resulting in G1-phase cell cycle accumulation in a dose-dependent manner. Simultaneously, the suppression of CDK2/cyclin E and induction of p21WAF1/Cip1 were correlated with Rb phosphorylation and c-Myc suppression. Taken together, we conclude that fargesin-mediated c-Myc suppression inhibits EGF-induced cell transformation and colon cancer cell colony growth by the suppression of retinoblastoma (Rb)-E2F and CDK/cyclin signaling pathways, which are mainly regulated by MAPK and PKB signaling pathways