Search Results (1,749)

Background/Objectives: Some skin tumors can extend beyond their clinical appearance. This presents an additional challenge, especially when the affected area is the genital region, which is more difficult for both the patient and the physician to access and monitor due to its location and anatomical characteristics. The treatment of these lesions is complex, and literature postulates Mohs surgery as the best therapeutic option. Methods: We describe our experience in two patients with the resection of vulvar lentiginous melanoma and genital extramammary Paget’s disease, using a method of deferred lateral margin control in the surgical treatment. Results: The “spaghetti technique”(ST) initially removing a small strip from all lateral margins of the lesion, which is then closed directly while awaiting the paraffin histological result. In a second stage, the tumors within those margins are removed, and immediate reconstruction is performed. The final oncological and functional result was satisfactory, with no notable side effects. Conclusions: This method is suited for large, poorly defined superficial tumors in the genital, perineal, and perianal regions, where a frozen section study would be slow and burdensome for the patient and surgeon. The ST preserves healthy tissue and can be performed by any surgeon and pathologist without additional training, and is more comfortable for patients, avoiding prolonged open wounds during multiple steps of tumor excision. Full article

Background/Objectives: This study aimed to evaluate the safety and efficacy of chitosan-based bioadhesive films for facilitating the topical delivery of curcumin in skin cancer treatment, addressing the pharmacokinetic limitations associated with oral administration. Methods: The films, which incorporated curcumin, were formulated using varying proportions of chitosan, polyvinyl alcohol, Poloxamer^® 407, and propylene glycol. These films were assessed for stability, drug release, in vitro skin permeation, cell viability (with and without radiotherapy), and skin irritation. Results: The films demonstrated physical stability and preserved curcumin content at room temperature for 90 days. Drug release was effectively controlled during the first 8 h, with release rates ranging from 51.6 ± 4.8% to 65.6 ± 13.0%. The films also enhanced drug penetration into the skin compared to a curcumin solution used as a control (stratum corneum: 1.3 ± 0.1 to 1.9 ± 0.8 µg/cm²; deeper skin layers: 1.7 ± 0.1 to 2.7 ± 0.2 µg/cm²). A cytotoxicity test on metastatic melanoma cells showed that curcumin at topical doses exerted activity similar to that delivered via the skin. Furthermore, curcumin alone was more effective in inhibiting tumor cells than radiotherapy alone (p < 0.01), with no additional benefit observed when curcumin was combined with radiotherapy. Finally, irritation tests confirmed that the films were safe for topical application. Conclusion: The developed chitosan-based bioadhesive films represent a promising alternative for the topical treatment of skin tumors using curcumin. Full article

Background/Objectives: Sentinel Lymph Node Biopsy (SLNB) aims at identifying clinically occult nodal metastases. It is the standard staging procedure for patients with T1b to T4 primary cutaneous melanoma. Moreover, it is recommended whenever the risk of a positive SLNB is >5%, according to the National Comprehensive Cancer Network Melanoma guidelines. When considering Non-Melanoma Skin Cancer (NMSC), the SLNB could play a role in tumors that mainly spreads via lymphatics, but strong evidence is missing. In this paper, the hot topics and controversies are reviewed; Methods: A PRISMA systematic review was carried out on the PubMed (MEDLINE) library from 2004–2024, searching for studies on SLNB in NMSC; Results: Seventy articles and 6379 patients undergoing SLNB for Squamous Cell Carcinoma (SCC), Merkel Cell Carcinoma (MCC), and Porocarcinoma were included. Overall, the SLNB positivity rate in these NMSCs was 24.4%, with an SNLB detection rate of 97.6%. Specifically, the SLNB positivity rate was 12.3% for high-risk cutaneous SCC, 24.4% for anogenital SCC, 29.3% for MCC, and 30.6% for Porocarcinoma. Most papers concluded that SLNB is safe, feasible, and significant in these malignancies; Conclusions: SLNB should be discussed and offered to every patient with MCC, and it should be discussed and considered in “high risk” SCC and Porocarcinoma for staging and prognostic purposes, aiming to identify a subgroup of patients who may benefit the most from early treatments. Full article

Background: Early-phase clinical trials offer a unique opportunity for patients with cancer. These trials often mandate biopsies to collect tumor tissue for research purposes, requiring patients to undergo invasive procedures. Some trials mandate molecular prescreening, but the success of these analyses relies on the quality and quantity of the tested materials. Additionally, bioptic procedures may result in complications. Methods: We retrospectively examined the records of patients referred to the Early Drug Development (EDD) Unit of the European Institute of Oncology who underwent biopsies for research purposes between January 2014 and December 2022. Our objective was to assess the safety of biopsy procedures and adequacy of the samples for NGS testing. Results: In total, 355 out of 731 patients (48.6%) underwent protocol-mandated biopsies. The most frequent sites of biopsy were the liver, lymph nodes, skin, and breast. Histological diagnosis was achieved in 349 (98%) patients, and NGS testing was successfully conducted in 111/127 (88.4%) cases. Of the 16 unsuccessful NGS attempts, 9 were performed on liver tissue. Unsuccessful NGS testing was attributed to poor sample quality and/or quantity, and the success rate varied significantly based on the specific tests attempted. Complications occurred in a small proportion of patients (4.8%), and none were serious. Conclusions: The non-negligible failure rate of NGS testing highlights the crucial need for implementing specific guidelines and Standard Operating Procedures for samples intended for NGS. With the use of a risk-based biopsy framework to guide clinical decisions, procedure-related complications may be minimized. Full article

In diagnostics, photons are used in basic methods such as computed tomography (CT) and positron emission tomography (PET), which are pivotal tools for high-resolution, non-invasive tumor detection, offering insights into tumor staging and progression. Mentioned techniques facilitate early diagnosis and the planning of therapeutic strategies. However, new methods are emerging, enhancing the precision and detail of diagnostics, such as ultra-weak photon emission (UPE) imagining, two-photon fluorescence imaging, photo acoustic imaging, and others. Therapeutically, external beam radiation therapy (EBRT) uses photons to target cancer cells while minimizing harm to healthy tissue. Photodynamic therapy (PDT), which uses light-sensitive compounds activated by specific wavelengths, represents a photon-based treatment applicable to certain malignancies. Other treatments include photo thermal therapy (PTT), radio dynamic therapy (RDT), intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), and more. These constantly evolving photon-driven technologies can be used to treat a broad spectrum of cancers, such as pancreatic, prostate, breast, and skin cancers. This review article discusses the latest photon-based methods in oncology, focusing on new possibilities, solutions, perspectives, and the potential disadvantages of these approaches. Full article

HPV-associated dermatological diseases include benign lesions like cutaneous warts and external genital warts. In addition, HPV infection is associated with the development of epithelial skin cancers, in particular cutaneous squamous cell carcinoma (cSCC). In contrast to anogenital and oropharyngeal cancers caused by mucosal HPV types of genus alpha papillomavirus, cSCC-associated HPV types belong to the genus beta papillomavirus. Currently available HPV vaccines that target mucosal HPV types associated with anogenital cancer and genital warts are type-specific and provide no cross-protection against beta HPV. When implementing vaccination to beta HPV to prevent skin tumors, it must be considered that acquisition of these HPV types occurs early in childhood and that the risk for cSCC increases with growing age and decreasing immune surveillance. Thus, individuals considered for beta HPV vaccination usually have pre-existing infection and are largely immunocompromised. On the other hand, worldwide increasing incidence rates of epithelial skin cancer reflect an urgent need for skin cancer prevention measures. Based on the pathogenic involvement of beta HPV, vaccination may represent a promising prevention strategy. Indeed, various procedures of prophylactic and therapeutic vaccination have been developed, and some of them have shown efficiency in animal models. Thus far, however, none of these vaccine candidates has been approved for application in humans. Full article

Combining anti-cancer agents in cancer therapies is becoming increasingly common because of their improved efficacy, reduced toxicity, and decreased risk of resistance development. Melanoma, a highly aggressive form of skin cancer characterized by limited treatment options due to chemoresistance, poses a considerable challenge for effective management. Here, we test the hypothesis that dietary supplements such as thymoquinone (TQ) and curcumin (CU) cooperatively modulate cancer-associated cellular mechanisms to inhibit melanoma progression. Through a series of in vitro experiments utilizing the A375 melanoma cell line, including assessments of cell viability, apoptosis, multicellular tumor spheroid models, reactive oxygen species (ROS) quantification, metabolomics analysis, and RNA sequencing, we established that the combined application of TQ and CU exhibited superior anti-tumor effects compared to their individual use. Our results indicate that the combination treatment significantly inhibited cell viability and induced apoptosis more effectively than either agent alone, with optimal synergy observed at concentrations of 25 µM CU and 10 µM TQ against A375 cells. Additionally, the combination treatment markedly elevated ROS levels, selectively activating the mitochondrial apoptotic pathway via caspase-9. Differential gene expression analysis further revealed a unique synergistic effect of the combination treatment, with enhanced regulation of genes related to oxidative stress and apoptosis. Notably, pathways such as mitochondrial apoptotic signaling and redox homeostasis were more effectively influenced by the combination, with genes such as GPX3, CYP4F11, and HSPB8 cooperatively regulated. Overall, the findings suggest that, in combination, TQ and CU acts synergistically against melanoma; however, further experimental and clinical studies are required to confirm its therapeutic potential. Full article

Cutaneous malignant melanoma (MM) is the most aggressive form of skin cancer, associated with high mortality and rising incidence rates in Europe despite prevention efforts. Nodular MM, the most aggressive subtype, often mimics other skin tumors, complicating diagnosis. We present the case of a 66-year-old woman with a large, ulcerated tumor beneath the left scapula, along with multiple nodular lesions on the left arm and chest. Initially suspected to be an aggressive squamous cell carcinoma, the diagnosis was confirmed as invasive cutaneous MM with a BRAF(V600) mutation via biopsy. Staging with PET/CT revealed extensive glucose metabolism in the tumors and surrounding tissues, as well as metastatic lymphadenopathy. The disease was classified as stage IV (T4bN3cM1a0). Neoadjuvant systemic therapy with BRAF and MEK inhibitors (Dabrafenib and Trametinib) was initiated to reduce tumor size. Remarkable regression was observed within a week, with further reduction in tumor size after one month. A follow-up PET/CT after 3 months showed significant decreases in tracer uptake and lesion size, with a ΔSUVmax of 51.9%, a ΔMTV of 74.5%, and a ΔTLG of 83.5%, indicating an excellent response to targeted therapy. Full article

Cancer is a leading cause of death, so continuous efforts into cancer therapy are imperative. In tumor cells, telomerase and oncogene activity are key points for uncontrolled cell growth. Targeting these processes with ligands that inhibit telomerase and/or reduce oncogene expression has been identified as a promising cancer therapy. This study evaluated the selectivity and affinity of the silver^II complex of 5,10,15,20-tetrakis(N-methyl-4-pyridinium)porphyrin (AgTMPyP) to stabilize DNA sequences capable of forming G4 structures mimicking the telomeric and oncogene regions, using spectroscopic, biochemical methods and in vitro assays. The tetracationic silver complex was compared with the free base, H₂TMPyP, and the zinc^II complex, ZnTMPyP. The results obtained from UV-Vis and fluorescence methods pointed to a great affinity and good selectivity of AgTMPyP to G4 structures, especially for the oncogene MYC. In general, an increase in the ability of the studied ligands for ¹O₂ generation when interacting with oncogenic and telomeric G4 sequences was found. The results of the PCR stop assays proved that AgTMPyP has the ability to inhibit Taq polymerase. Additionally, in vitro assays demonstrated that the silver^II complex exhibits low cytotoxicity against HaCaT— an immortalized, non-tumorigenic, skin keratinocytes cell line—and, although nonexclusive, AgTMPyP shows nuclear co-localization. Full article

Malignant melanoma is one of the most important dermatological neoplasms. The high mortality rate associated with this skin disease is primarily due to the occurrence of metastases, while the diagnosis and treatment of melanoma in its early stages has a favorable prognosis. Early detection is crucial because the success of treatment is directly related to the depth of cancerous growth. The family of matrix metalloproteinases (MMPs) plays a critical role in the initiation and progression of melanoma. Prominent MMPs, including MMP-1, MMP-2, MMP-3, MMP-9, MMP-13, and MMP-14, have been shown to significantly contribute to the development of melanoma. The tumor microenvironment, particularly the extracellular matrix (ECM), has emerged as a critical factor in modulating cancer progression. This review focuses on the role of matrix metalloproteinases and their inhibitors in ECM degradation and the subsequent progression of melanoma, as well as their potential as therapeutic targets. Full article

Vulvar carcinoma is a rare disease, meeting the criteria for a “rare cancer”, but its incidence is increasing, especially in women <60 years of age. Squamous cell carcinoma (VSCC) accounts for the overwhelming majority of vulvar carcinomas and is the focus of this review. As with many cancers, the increased understanding of molecular events during tumorigenesis has led to the emergence of the molecular subclassification of VSCC, which is subclassified into tumors that arise secondary to high-risk human papillomavirus infection (HPV-associated, or HPVa) and those that arise independently of HPV (HPVi), most commonly in the setting of a chronic inflammatory condition of the vulvar skin. This latter group of HPVi VSCC arises in most cases secondary to mutations in TP53, but recently, attention has focused on the uncommon TP53 wild-type HPVi VSCC. These three molecular subtypes of VSCC (HPVa, HPVi p53 abnormal, and HPVi p53 wild type), as well as their precursor lesions, cannot be diagnosed based on a routine histopathological examination or immunostaining for p53 and p16 as surrogate markers for TP53 mutation and high-risk HPV infection, respectively, are required. The molecular subtyping of VSCC shows high reproducibility and provides important prognostic information. HPVa VSCC has the most favorable prognosis, while HPVi VSCC with TP53 mutations (p53abn) has the worst prognosis, and HPVi VSCC with wild-type TP53 (p53wt) has an intermediate prognosis. In this review, we discuss the evidence supporting this molecular subclassification and its implications for the diagnosis and treatment of VSCC and its precursors. Full article

A seven-year-old spayed female dog presented with multiple, small oval-shaped masses on the abdominal skin. The excised tissue was submitted for histopathological evaluation. Routine histology revealed basaloid nodules with stippled chromatin and pleomorphic nuclei. Morphologically, the tumor resembled a solid papillary carcinoma of the breast or an endocrine mucin-producing sweat gland carcinoma (EMPSGC). EMPSGC is a rare neuroendocrine-differentiated neoplasm. This study aimed to compare different immunohistochemical markers for distinguishing between canine sweat gland carcinoma (SGC) and mammary gland carcinoma (MGC). CK19 and Sox9 were useful in identifying SGC. Additionally, the tumor was positive for CK5, AE1/AE3+CK8/18, p63, vimentin, E-cadherin, and synaptophysin, while estrogen receptor staining was negative. The final diagnosis of canine EMPSGC was based on the tumor’s morphological and neuroendocrine immunohistopathological features. Our report provides the first detailed description of a canine EMPSGC, an exceedingly rare tumor in dogs. Full article

Cutaneous squamous cell carcinoma (CSCC) in dogs is a locally invasive tumor that typically occurs in areas of poorly pigmented skin due to sun exposure. Identifying new biomarkers, such as syndecan-1 (CD138) and E-cadherin, is fundamental for tumor diagnosis and prognosis. Dysregulation of syndecan-1, expressed in epithelial tissue, fibroblasts, and plasma cells, is associated with poor prognosis in several types of cancer. Similarly, E-cadherin, which plays a crucial role in cell adhesion and epithelial functionality, is also linked to adverse outcomes. This study evaluated the expression of syndecan-1 and E-cadherin in 47 cases of canine cutaneous squamous cell carcinoma. The results showed that the intensity of syndecan-1 decreased with increasing tumor aggressiveness, and its presence in the stroma was significantly associated with tumor grade. E-cadherin also demonstrated a decrease in intensity with increasing malignancy. However, the association between syndecan-1 and E-cadherin was not statistically significant. E-cadherin reduction and stromal syndecan-1 positivity seem to be associated with tumor aggressiveness in canine cutaneous squamous cell carcinoma. Further studies are needed to explore their roles in tumor progression. Full article

Background/Objective: Ultraviolet (UV) B radiation leads to DNA damage by generating cyclobutane pyrimidine dimers (CPDs). UVB-induced CPDs can also result in immune suppression, which is a major risk factor for non-melanoma skin cancer (NMSC). UVB-induced CPDs are repaired by nucleotide repair mechanisms (NER) mediated by xeroderma pigmentosum complementation group A (XPA). The purpose of this study was to investigate the use of TH as a chemopreventive agent against the development of skin cancer. Method: SKH-1 hairless mice were exposed were fed with TH (0.1% v/v) for two weeks and exposed to a single dose of UVB (180 mJ/cm²). Dorsal skin was harvested 24 h post-UVB exposure for evaluation of DNA damage and repair. Lymph nodes were also harvested to prepare single cell suspension for flow cytometric evaluation. For carcinogenesis experiments, SKH-1 hairless mice were given TH (0.1% v/v) ad libitum and exposed to UVB (180 mJ/cm²) thrice a week for 30 weeks. Results: Feeding SKH-1 hairless mice with TH (0.1% v/v) for two weeks prior to a single dose of UVB (180 mJ/cm²) led to a significant increase in XPA in skin and DNA repair cytokines IL-12 and IL-23 in draining lymph nodes. Furthermore, when subjected to the photocarcinogenesis protocol; mice fed with TH developed significantly fewer tumors in comparison to mice fed on drinking water. Conclusions: Our data demonstrate that TH has a protective effect against UVB-induced DNA damage, immune suppression, and skin cancer. Future studies will further investigate the potential of TH as a preventive treatment for NMSC. Full article

With technological advancements, remarkable progress has been made with the convergence of health sciences and Artificial Intelligence (AI). Modern health systems are proposed to ease patient diagnostics. However, the challenge is to provide AI-based precautions to patients and doctors for more accurate risk assessment. The proposed healthcare system aims to integrate patients, doctors, laboratories, pharmacies, and administrative personnel use cases and their primary functions onto a single platform. The proposed framework can also process microscopic images, CT scans, X-rays, and MRI to classify malignancy and give doctors a set of AI precautions for patient risk assessment. The proposed framework incorporates various DCNN models for identifying different forms of tumors and fractures in the human body i.e., brain, bones, lungs, kidneys, and skin, and generating precautions with the help of the Fined-Tuned Large Language Model (LLM) i.e., Generative Pretrained Transformer 4 (GPT-4). With enough training data, DCNN can learn highly representative, data-driven, hierarchical image features. The GPT-4 model is selected for generating precautions due to its explanation, reasoning, memory, and accuracy on prior medical assessments and research studies. Classification models are evaluated by classification report (i.e., Recall, Precision, F1 Score, Support, Accuracy, and Macro and Weighted Average) and confusion matrix and have shown robust performance compared to the conventional schemes. Full article