RESUMEN

The present research explores the cytotoxic mechanism of protein Cytochrome P450 (CYP3A4) with aflatoxin (AFB1), a potent carcinogen. Cytochrome P450 is an essential enzyme involved in drug metabolism, however epoxide formation due to the binding event of AFB1 leads to cell cytotoxicity. In this direction, our study elucidates the scavenging effect of algal derived Sodium Copper Chlorophyllin (SCC) over AFB1 cytotoxicity. Cyanobacteria/ microalgae derived SCC have garnered attention due to its diverse applications in pharmacological and food industries. This work began with production of SCC from Spirulina and Chlorella sp. over a stipulated period of growth. Subsequently, the study delved into the interplay between SCC and the carcinogenic impact of AFB1 on the CYP3A4 enzyme. Computational studies demonstrated SCC binding and blocking mechanisms against AFB1. Our research intended to determine whether CYP3A4 can bind to SCC that in turn acts as an interceptor for AFB1, or influences the metabolism of bound AFB1. Current results support that SCC is an effective AFB1 trap as it shows interactions with AFB1. These findings would open-up new avenue in clinical biology/pharmacology to further explore the mechanisms of action of CYP3A4 with AFB1 and SCC, offering promising prospects for abating cell cytotoxicity.

RESUMEN

BACKGROUND: Squamous cell carcinoma (SCC) of presumed lung origin (PLO) is now the second most frequent histologic subtype of non-small cell carcinoma after adenocarcinoma. The use of clinic-genomic correlation provided by comprehensive genomic profiling (CGP) can revise clinicopathologic diagnoses of presumed primary lung SCC (PLO-SCC) to diagnoses of metastatic SCC of cutaneous origin (C-SCC). DESIGN: A total of 10 146 samples of clinically advanced PLO-SCC (84% known Stage IV) passed QC metrics and were designated as PLO-SCCs by review of test requisition forms, clinical notes, and pathology reports. One thousand seven hundred sixty-one cases of known primary C-SCC were also included in this study. All samples underwent hybrid capture-based CGP (Foundation Medicine, Inc.) using a targeted gene panel to evaluate all classes of genomic alterations (GA), determine MSI, TMB, and genomic ancestry status. The mutational signature (MS) of each case was called by the decomposition method using reference signatures in the COSMIC database. PD-L1 tumor cell expression was determined by IHC (22C3; Dako). All results were compared using the Fisher exact method with the false discovery rate corrected with a Benjamini-Hochberg adjustment. RESULTS: A total of 253 of 10 146 (2.5%) PLO-SCC cases featured a UV+ MS; 812 of 1761 C-SCC (46.1%) that also featured a UV radiation exposure MS (UV+) were also included in this study. PLO-SCC UV+ cases used for sequencing included tissue samples from the lung (162), lymph node (34), soft tissue (33), liver (8), head and neck (7), brain (5), and skin thought to be metastatic sites from primary lung SCC (4). The PLO-SCC UV+ patients were 78.7% male and had a median age of 72 years, which was younger and more frequently male gender than both the C-SCC UV+ and C-SCC UV- patients (p < 0.0001). Both the PLO-SCC UV+ and C-SCC UV+ featured greater GA per tumor than the PLO-SCC UV- cases (p < 0.0001). In the PLO-SCC UV- cases, tobacco exposure and APOBEC were the most frequent MSs. For the biomarkers associated with immune checkpoint inhibitor efficacy, when compared with the PLO-SCC UV- cases, the PLO-SCC UV+ cases featured more cases with TMB ≥10 mutations/Mb (88.5% vs. 36.5%; p < 0.0001) and ≥20 mutations/Mb (66.8% vs. 6.8%; p < 0.0001) and a trend for less frequent positive PD-L1 (≥50% TPS) IHC staining (30.2% vs. 39.6%; p = 0.062). Compared to PLO-SCC UV- cases, PLO-SCC UV+ and C-SCC UV+ cases were more likely to harbor clinically-actionable GA in PTCH1 and NOTCH1/2 (p < 0.0001) and less likely to harbor clinically-actionable GA in KRAS, PIK3CA, and PTEN (p < 0.0001). The frequency of PTCH1 GA in PLO-SCC UV+ (32% vs. 0.9% in PLO-SCC UV-) suggested that PLO-SCC UV+ may include a mixture of C-SCC and cutaneous basal cell carcinomas (C-BCC) with squamous differentiation. CONCLUSIONS: When cases of PLO-SCC undergo CGP, a small 2.5% subset of cases that featured a UV MS emerge that indicates that these tumors may actually represent metastatic cutaneous SCC or BCC with squamous differentiation. Given the significant treatment and clinical impact associated with the resolution of the true diagnosis of these cases, the use of genomic sequencing in PLO-SCC may be clinically beneficial.

RESUMEN

Leukoplakia, a potentially malignant oral condition, manifests as a nonremovable white lesion that is often linked to risk factors such as smoking, alcohol, and HPV. Pegylated liposomal doxorubicin (PLD), which is used in cancer treatment, has been associated with secondary oral cancers, particularly in patients with leukoplakia. A case study revealed the development of squamous cell carcinoma (SCC) on the tongue following PLD treatment, suggesting a potential link between the drug and malignant transformation. Despite the benefits of PLD in reducing cardiac toxicity, long-term oral monitoring is essential due to the persistent risk of oral cancer posttreatment.

RESUMEN

Oropharyngeal squamous cell carcinoma (OPSCC) related to human papillomavirus (HPV) infection has better survival outcomes compared to non-HPV-related OPSCC, leading to efforts to de-escalate the intensity of treatment to reduce associated morbidity. This article reviews recent clinical efforts to explore different de-escalation frameworks with a particular emphasis on the emergence of transoral robotic surgery and surgically driven de-escalation approaches. It discusses the current evidence for incorporating surgery into an evolving treatment paradigm for HPV-related OPSCC.

Asunto(s)

RESUMEN

GCA, also known as Buschke-Lowenstein tumor, is a rare sexually transmitted disease associated with HPV types 6 and 111. These warts are considered histologically benign, but there is a risk of localized invasion and development of malignancy. This malignant transformation occurs most often in the perianal and vulvar areas, and involvement of other sites is relatively rare2. In this case, we report a rare case of a giant wart originating from breast skin infected with HPV and progressing to cutaneous squamous cell carcinoma.

RESUMEN

Aim: This study investigated RAP1 immunostaining variation in different cell types during CC progression.Methods: Paraffin-embedded cervical tissues from 101 patients were categorized into control, pre-neoplastic and neoplastic groups. RAP1 immunolocalization, HPV detection and genotyping were performed. A semiquantitative immunoreactive score was employed to compare labeling intensity, cellular localization, nuclear labeling, percentage and distribution of reactive cells.Results: 73% (72/99) of cervical specimens were HPV+. RAP1 was localized in the nucleus and cytoplasm of all samples. Cytoplasmic RAP1 immunoscore was higher than nuclear score in all CC groups. RAP1 intensity increased with lesion severity. SCC samples exhibited predominantly intense RAP1 immunostaining.Conclusion: RAP1 is an efficient biomarker for detecting invasive CC lesions but has limited utility in distinguishing SCC grades.

[Box: see text].

RESUMEN

Primary squamous cell carcinoma (SCC) of the liver, a notably uncommon type of cancer, is frequently linked with diverse hepatic conditions including hepatic cysts, hepatolithiasis, and hepatic teratoma. Literature indicates that only approximately 30 cases of primary SCC of the liver have been documented. Herein, we report a 54-year-old previously healthy patient who was presented with cholangitis symptoms. Examinations revealed normal vitals. However, deranged liver function with transaminitis and hyperbilirubinemia were noticed. A CT scan showed a hepatic mass with bile duct dilation. Biopsy confirmed hepatic squamous cell carcinoma, leading to chemotherapy treatment. Despite treatment, the survival outcomes for this cancer remain limited, and the prognosis is generally unfavorable.

RESUMEN

Cohesins promote proper chromosome segregation, gene transcription, genomic architecture, DNA condensation, and DNA damage repair. Mutations in either cohesin subunits or regulatory genes can give rise to severe developmental abnormalities (such as Robert Syndrome and Cornelia de Lange Syndrome) and also are highly correlated with cancer. Despite this, little is known about cohesin regulation. Eco1 (ESCO2/EFO2 in humans) and Rad61 (WAPL in humans) represent two such regulators but perform opposing roles. Eco1 acetylation of cohesin during S phase, for instance, stabilizes cohesin-DNA binding to promote sister chromatid cohesion. On the other hand, Rad61 promotes the dissociation of cohesin from DNA. While Eco1 is essential, ECO1 and RAD61 co-deletion results in yeast cell viability, but only within a limited temperature range. Here, we report that eco1 rad61 cell lethality is due to reduced levels of the cohesin subunit Mcd1. Results from a suppressor screen further reveals that FDO1 deletion rescues the temperature sensitive (ts) growth defects exhibited by eco1 rad61 double mutant cells by increasing Mcd1 levels. Regulation of MCD1 expression, however, appears more complex. Elevated expression of MBP1, which encodes a subunit of the MBF transcription complex, also rescues eco1 rad61 cell growth defects. Elevated expression of SWI6, however, which encodes the Mbp1-binding partner of MBF, exacerbates eco1 rad61 cell growth and also abrogates the Mpb1-dependent rescue. Finally, we identify two additional transcription factors, Fkh1 and Fkh2, that impact MCD1 expression. In combination, these findings provide new insights into the nuanced and multi-faceted transcriptional pathways that impact MCD1 expression.

RESUMEN

Circulating tumor cells (CTCs) have significant potential to become an important tool for monitoring the effects of treatment in solid tumors. The present study reports the occurance of CTCs in cervical cancer (CC) patients during radical chemoradiotherapy (CRT), including brachytherapy (BRT), and during the follow-up period. Patients diagnosed with CC treated with radical CRT were included in the study (n=30). A total of 167 CTC-tests (MetaCell®) were provided at predefined testing time points during the study follow-up (e.g., before CRT, after CRT, every three months of follow-up). In parallel with CTC-testing, SCC-Ag were measured to compare their predictive values during treatment. CTCs were present in 96% (25/26) of patients at the time of diagnosis and in 61% (14/23) after treatment. Patients who relapsed during the 36-month follow-up (n=10) showed an elevation in pre-treatment CTC- numbers, similarly there was a significant increase in pre-treatment SCC-Ag. As next, an increased number of CTCs was observed approximately 12 weeks before relapse was diagnosed by standard imaging modalities (MRI, US, PET-CT) in 3 of 4 patients. In addition to standardized vital cytomorphology of enriched CTCs, quantitative PCR (qPCR) was used to inform the nature of CTCs before treatment. Analysis revealed increased SOX2 and POUSF expression in CTCs in the group of patients with recurrence (P < 0.02). Disease aggressiveness may be related to increased expression of stem cell markers, as found in samples from relapsed patients. CTCs may be an aid to assess tumor burden and disease aggressiveness. An increase in CTCs precedes an increase in SCC-Ag and confirmation of relapse by imaging, as shown in our study.

RESUMEN

OBJECTIVES: Laryngeal squamous cell carcinoma (SCC) is a predominantly male illness. Although the rate of female patients increased, a knowledge gap exists in the medical literature regarding gender-based differences. DESIGN: Retrospective cohort study. SETTING: Adult patients treated for laryngeal SCC in a tertiary medical centre between 2006 and 2020. Data were collected on demographics, clinical presentation, treatment modalities, disease recurrence and survival status. PARTICIPANTS: Two hundred ninety-one patients with laryngeal SCC, 50 (17.2%) females and 241 (82.8%) males. MAIN OUTCOME MEASURES: Disease-specific survival (DSS), overall survival (OS) and disease-free survival (DFS), as well as differences in disease characteristics and treatment modalities. RESULTS: Tumour subsites differed significantly between females and males (36% vs. 19.5% supraglottic, 62% vs. 80.5% glottic and 2% vs. 0% subglottic, respectively; p = 0.006). Females were diagnosed at younger ages (61.7 ± 10.58 vs. 65.87 ± 11.11 years, p = 0.016) and advanced-stage disease (58% vs. 39.4%, p = 0.018). Females were treated with combined modalities at higher rates (36% vs. 54.8% for single modality, p = 0.031). DSS rates did not differ between genders (log-rank p = 0.12). Despite being diagnosed at more advanced disease stages, females demonstrated prolonged median OS compared to males (130.17 vs. 106.17 months, log-rank p = 0.017). No significant differences in DFS were observed (log-rank p = 0.32). In a multivariate Cox proportional hazards model, male gender remained an independent negative OS predictor (HR = 2.08; CI, 1.10-3.96; p = 0.025), along with increasing age (HR = 1.06; CI, 1.04-1.09; p < 0.001) and advanced disease stage (HR = 1.7; CI, 1.08-2.67; p = 0.023). CONCLUSIONS: Our findings suggest the importance of considering gender-specific factors in the management of laryngeal SCC.

RESUMEN

​Head and neck squamous cell carcinomas (HNSCC) are common malignancies that can metastasize to various distant sites. Cardiac metastasis (CM) from a primary HNSCC is an extremely rare finding that presents a significant challenge due to its association with a poor prognosis and limited treatment options. Due to their rare occurrence, there is no clear consensus on how to diagnose and manage such cases. In this article, we review a patient with complicated CM from buccal squamous cell carcinoma, which was incidentally detected by fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT).

RESUMEN

INTRODUCTION: Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers worldwide. Due to the ever-increasing sun exposure and life expectancy, cSCCs are increasing worldwide. The aim of our study was to identify specific risk factors leading to local and regional recurrences, determine patients' survival rates, and identify best practices for the management of cSCC. METHODOLOGY: This study retrospectively analyzed 1197 head and neck cSCCs in 945 patients who consecutively presented to the clinics from January 2007 to December 2016. Patients were followed up for a minimum of 18 months. RESULTS: A total of 29 patients (3%) developed loco-regional recurrences (26 local, one regional, and two both local and regional) with a median time to recurrence of 25 (range, 1-81) months. The mean follow-up was 32 (range, 5-90) months. Treatment modality (p=0.027), depth of invasion (p<0.001), diameter > 20 mm (p<0.001), gender (p=0.022), histological differentiation (p<0.001), site of the lesion (p<0.001), perineural and intravascular invasion (p<0.001), positive lymphadenopathy (p=0.021), immunosuppression (p<0.001), and history of treatment (p=0.008) proved to be strong predictors for loco-regional recurrences. At one and five years after diagnosis, 95.6% and 59.9% of all patients were recurrence-free, respectively. The median survival time from recurrence was 2.6 years. CONCLUSION: Our study identifies prognostic indicators for reoccurrence by analyzing data from a large continuous cohort in the management of cSCCs.

RESUMEN

PURPOSE: Neuroendocrine carcinoma of the cervix (NECC) is rare but results in poor prognosis. The causes of death (CODs) in NECC patients are rarely reported. Our study aimed to explore the distributions of death causes of NECC patients compared with squamous cell carcinoma (SCC) and adenocarcinoma (ADC) and to develop a validated survival prediction model. METHODS: Patients diagnosed with NECC, SCC, or ADC were identified from the Surveillance, Epidemiology, and End Results Program database from 1975 to 2019. We analyzed the standardized mortality ratio (SMR) to determine each cause of death for each survival time category. The Kaplan-Meier method was used for survival analysis. Univariate and multivariate Cox regression analyses were used to establish a nomogram model. RESULTS: A total of 358 NECC patients were included in this study, and 270 (75.4%) died during the follow-up period. Patients with NECC had 5.55 times (95% CI, 4.53-6.79, p < 0.0001) higher risk of death compared with patients with SCC and 10.38 times (95% CI, 8.28-13.01, p < 0.0001) higher compared with ADC. Cervical cancer is the main cause of death in NECC. As the diagnosis time increased, the risk of death from all causes and cervix cancer gradually decreased. While after at least 10 years of follow-up time, the highest and most dramatical SMR values were observed for metastasis (SMR, 138.81; 95% CI, 37.82-355.40; p < 0.05) and other cancers as the reason for death has an over 7-fold higher SMR (SMR: 7.07; 95% CI: 2.60-15.40, p < 0.05) more than 5 years after the cancer diagnosis. Race, FIGO stage, and surgery were independent risk factors for the overall survival (OS) of NECC patients. For the predictive nomogram, the C-index was 0.711 (95% CI: 0.697-0.725) and was corrected to 0.709 (95% CI: 0.680, 0.737) by bootstrap 1000 resampling validation. CONCLUSION: Compared with SCC and ADC, NECC patients have an elevated risk of mortality due to cervical cancer and metastasis. We successfully constructed a prognostic nomogram for patients with NECC. Based on refractoriness and high mortality of NECC, targeted treatment strategies and follow-up plans should be further developed according to the risk of death and distribution characteristics of CODs.

Asunto(s)

RESUMEN

PURPOSE: Our aim was to assess the ability of simultaneous immunohistochemical staining (IHC) for p16 and p53 to accurately subclassify head and neck squamous cell carcinomas (HNSCC) as HPV-associated (HPV-A) versus HPV-independent (HPV-I) and compare p53 IHC staining patterns to TP53 mutation status, p16 IHC positivity and HPV status. METHODS: We stained 31 HNSCCs for p53 and p16, and performed next-generation sequencing (FoundationOne©CDx) on all cases and HPV in-situ hybridization (ISH) when sufficient tissue was available (n = 23). p53 IHC staining patterns were assessed as wildtype (wt) or abnormal (abn) patterns i.e. overexpression, null or cytoplasmic staining. RESULTS: In a majority of cases (28/31) interpretation of p16 and p53 IHC was straightforward; 10 were considered HPV-A (p16+/p53wt) and 18 cases were HPV-I (p16-/p53abn). In the remaining three tumours the unusual immunophenotype was resolved by molecular testing, specifically (i) subclonal p16 staining and wild type p53 staining in a tumour positive for HPV and with no TP53 mutation (HPV-A), (ii) negative p16 and wild type p53 staining with a TP53 mutation and negative for HPV (HPV-I), and (iii) equivocally increased p16 staining with mutant pattern p53 expression, negative HPV ISH and with a TP53 mutation (HPV-I). CONCLUSION: Performing p16 and p53 IHC staining simultaneously allows classification of most HNSCC as HPV-A (p16 +, p53 wild type (especially basal sparing or null-like HPV associated staining patterns, which were completely specific for HPV-A SCC) or HPV-I (p16 -, p53 mutant pattern expression), with the potential for limiting additional molecular HPV or mutational testing to selected cases only.

Asunto(s)

RESUMEN

Introduction: Annona muricata contains acetogenins, which have shown promising anticancer activity against various cell lines. This study aims to evaluate and compare the anticancer activity of the crude extract of Annona muricata and its nano formulation on Squamous Cell Carcinoma-25 (SCC-25) oral cancer cell lines. Methods: The crude extract of Annona muricata was prepared using standard extraction techniques, while its nano formulation was synthesized through nanoparticle fabrication methods. Authenticated SCC-25 cell lines were obtained from ATCC and cultured and treated with varying concentrations of both the crude extract and nano formulation. Cell viability assays, apoptosis assays, Cell Cycle assay, ROS, and MMP analysis techniques were employed to assess the anticancer activity and mechanism of action. Results: In the MTT assay, the Annona formulation treated cells exhibited lower IC50 values compared to the crude extract treated SCC-25 cell lines. In the cell cycle assay, the Annona crude extract induced higher cell cycle arrest in the G1 phase in SCC-25 cell lines compared to the control. The nano formulation of Annona demonstrated significantly higher cell cycle arrest in G1 phase compared to both the control and the Annona crude extract-treated SCC-25 cell lines. The crude extract showed less apoptotic activity in apoptosis assay when compared to control, whereas the Annona formulation exhibited higher late apoptosis compared to the control, indicating the potential anticancer properties of Annona. The mean fluorescent intensity test of SCC-25 oral cancer cells treated with Annona crude extract and Annona formulation showed a significant loss of Mitochondrial membrane potential compared to the control. The percentage of MMP was lower in Annona-treated cells, while the Annona formulation treated cells showed similar results to the control. The mean fluorescent intensity of ROS in SCC-25 oral cancer cells treated with Annona crude extract and Annona formulation showed significantly lower Reactive oxygen species production compared to the control. The percentage of ROS was lower in Annona treated cells compared to the formulation, but the Annona formulation-treated cells showed lower values than the control. Conclusion: In conclusion, both the crude extract and nano formulation of Annona muricata possess potent anticancer activity against SCC-25 oral cancer cell lines. However, the nano formulation exhibited superior efficacy, suggesting its potential for further development as a therapeutic agent for oral cancer treatment.

RESUMEN

Mandibular continuity defects can result in varying degrees of cosmetic disfigurement. Restoration of form and function may require surgical reconstruction of the affected area. While surgical reconstruction may improve the overall prognostic outcomes for the patient, the definitive prosthetic phase can commence only after a substantial time lag for adequate hard/soft tissue healing. This interim phase often challenges the patient's masticatory ability. The traditional reconstruction of hemimandibulectomy defects has its own limitations. This case report describes the fabrication of a 3D-printed bite splint for a patient with limited mouth opening and significant malocclusion due to surgical over-correction. The prosthesis given served as an appliance to improve the masticatory ability of the patient.