Cutaneous Cancer Research Articles

FGFR2 in the Development and Progression of Cutaneous Squamous Cell Cancer.

Cutaneous squamous cell carcinoma (cSCC) is an increasingly common malignancy of the skin and the leading cause of death from skin cancer in adults over the age of 85. Fibroblast growth factor receptor 2 (FGFR2) has been identified as an important effector of signaling pathways that lead to the growth and development of cSCC. In recent years, there have been numerous studies evaluating the role FGFR2 plays in multiple cancers, its contribution to resistance to anticancer therapy, and new drugs that may be used to inhibit FGFR2. This review will provide an overview of our current understanding of FGFR2 and potential mechanisms in which we can target FGFR2 in cSCC. The goals of this review are the following: (1) to highlight our current knowledge of the role of FGFR2 in healthy skin and contrast this with its role in the development of cancer; (2) to further explain the specific molecular mechanisms that FGFR2 uses to promote tumorigenesis; (3) to describe how FGFR2 contributes to more invasive disease; (4) to describe its immunosuppressive effects in skin; and (5) to evaluate its effect on current anticancer therapy and discuss therapies on the horizon to target FGFR2 related malignancy.

Relapsing Cutaneous Metastatic Breast Cancer: A Clinical Conundrum.

Relapsing Cutaneous Metastatic Breast Cancer: A Clinical Conundrum.

Keratinocyte Carcinoma: Canadian Landscape and an Evidence-based Approach to Follow-up

Dermatologists play a vital role in the early detection, prevention and effective management of skin cancer in patients with a prior history of the disease. Regular monitoring and timely interventions greatly enhance the overall prognosis and quality of life for patients with skin cancer. Dermatologists possess the requisite expertise to accurately diagnose and oversee the management of cutaneous skin cancers. Skin cancer screening via total body skin exam (TBSE) is often considered one of the safest, easiest, and most cost-effective tests in medicine. Despite dermatologists’ ability to offer such invaluable care for this patient population, offering routine skin checks for all patients with a prior history of skin cancer becomes exceptionally challenging given the high demand for dermatology care across Canada. It is important for dermatologists to maximize the efficiency of care during TBSEs by adhering to evidence-based guidelines when determining the frequency and duration of follow-up. These guidelines also provide a solid foundation for discussions with patients regarding the rationale for discharge back to their primary care provider.

Grover's Disease Association with Cutaneous Keratinocyte Cancers: More than a Coincidence?

Better mechanistic understanding of desmosome disruption and acantholysis in Grover's disease (GD) may improve management of this disease. Recent molecular studies highlighted promising pathways to be explored by directly comparing GD and selected features of associated skin diseases. The association between GD and cutaneous keratinocyte carcinomas, the most prevalent non-melanoma skin cancers (NMSC), is not completely characterized. To review the medical literature regarding GD-associated cutaneous keratinocyte cancers, focusing on molecular features, pathophysiological mechanisms, and disease associations, to help guide future research and patient management. GD has been associated with a variety of skin conditions, but its association with skin cancers has been rarely reported. Between 1983 and 2024, only nine scientific papers presented data supporting this association. Interestingly, we found that GD may mimic multiple NMSCs, as few authors reported GD cases misdiagnosed as multiple cutaneous squamous cell carcinomas for more than 4 years or the presence of superficial basal cell carcinoma-like areas associated with focal acantholysis. In conclusion: (a) GD may be an imitator of multiple NMSCs, and (b) the relationship between GD and NMSCs may reveal promising pathways for the mechanistic understanding of desmosome disruption and acantholysis in GD and may even lead to its reclassification as a distinctive syndrome.

Dermoscopy of skin metastases in advanced cancer-systemic (visceral, hematologic) and cutaneous.

Skin metastases arise in 10% of cancer patients, but standardized dermoscopy diagnostic criteria for skin metastases remain poor. This study's objective was to analyze the dermoscopy features of skin metastases from advanced systemic and cutaneous cancers. A retrospective study on 715 dermoscopy images of skin metastases from 33 patients with various primary cancers (breast, ovary, melanoma, non-melanoma skin cancer, and chronic leukemia) attending two academic centers between 2013 and 2023 was performed. Four independent observers blindly analyzed patterns, colors, vessels, and elementary lesions for each metastasis (30 parameters in total). The structureless white pattern was the most prominent indicator of cutaneous metastasis (81.26%, p < 0.001). Regardless of the primary tumor, colors pink, red, white, and tan were identified. Elementary lesions were infrequent, except for melanoma metastases that displayed dots (13.23%) and globules (11.11%). Breast cancer metastases presented: blue (41.48%) and red (34.32%) colors, irregular vessels (13.58%), and a blue-naevus pattern (22.22%). Melanoma metastases displayed: a blue-naevus pattern (61.38%), a blue color (85.71%), and a structureless-blue combination pattern (79.37%). Non-melanoma skin cancer metastases were characterized by vascular (42.11%) and angioma-like (31.58%) patterns, pink (57.89%) and red (57.89%) colors, irregular (57.89%), thin hairpin (47.37%), comma (47, 37%), and thick hairpin (26, 32%) vessels and a red, white and irregular vessels combination pattern (52, 63%). A pink structureless combination pattern was frequent (61.05%) in chronic leukemia metastases. Ovarian cancer metastases displayed a white and tan structureless combination pattern (100%) and frequently had dotted vessels (42.85%). Papules and nodules with a white structureless pattern suggest skin metastases, regardless of the primary tumor. A blue structureless lesion is indicative of melanoma metastasis and a vascular pattern with irregular vessels indicates a non-melanoma skin cancer metastasis. Dermoscopy stands as a reliable non-invasive diagnostic method for suspected cutaneous metastases in patients with a known cancer history.

Chemoreactive 2,5-Diketopiperazines from a Penicillium sp., Structure Revision of Reported Analogues and Proposed Facile Transformation Pathways.

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous cancer. Two new prenylated indole 2,5-diketopiperazine alkaloids, brevianamides E1 (1) and E2 (2), were isolated from a Penicillium fungus. Both compounds showed moderate cytotoxic activity against select MCC cell lines (i.e., MCC13, MKL-1, UISO, and WaGa) in the low micromolar range. The relative and absolute configurations of 1 and 2 were determined by combined approaches, including NOESY spectroscopy, DFT ECD and DP4 plus calculations, and Marfey's reaction. Literature research and the comparison of NMR and ECD data led to the structure revision of three previously reported natural analogues, notoamides K and P and asperversiamide L. The structurally unstable 1 and 2 underwent steady interconversion under neutral aqueous conditions. Investigation of the degradation of 2 in acidic methanol solutions led to the identification of a new methoxylated derivative (6) and two new ring-opened products (7 and 8) with the rearranged, elongated, 4-methylpent-3-ene side chain. The facile transformation of 2 to 7 and 8 was promoted by the intrinsic impurity (i.e., formaldehyde) of HPLC-grade methanol through the aza-Cope rearrangement.

Cancer incidence following bariatric surgery in renal transplant recipients: a retrospective multi-center analysis

BackgroundObesity, a known independent risk factor for developing malignancy. Additionally, renal transplant recipients (RTR) confer a 2- to 4-fold increased risk of overall malignancies with an excess absolute risk of .7% per year. While transplant recipients are at risk for obesity and malignancy, the effect of bariatric surgery (BS) in the posttransplantation setting is not well known. ObjectivesOur study primarily evaluated the impact of BS on cancer incidence in RTR with severe obesity in the posttransplantation setting. Weight loss outcomes were analyzed secondarily. SettingUniversity Hospital. MethodsA retrospective study using TriNetX database was developed to analyze cancer outcomes in RTR with posttransplantation BS versus RTR without BS from 2000 to 2023. After the exclusion process and propensity matching, both cohorts consisted of 153 patients. ResultsRTR-BS had a significantly lower incidence of overall cancer and transplant-related cancers (P < .05). No significant difference was identified in cutaneous, gastrointestinal, and reproductive cancers. Percent Excess Weight Loss (%EWL) was significantly lower in RTR-only cohort (11.4%) versus RTR-BS cohort (57.8%) at 5 years. Sleeve gastrectomy (SG) patients (73.19%) had significantly higher %EWL than Roux en-Y gastric bypass (RYGB) patients (49.33%) at 3 years. No difference in cancer incidence was noted between SG and RYGB patients. ConclusionPostrenal transplantation BS had a diminishing effect on overall and transplant-related cancer incidence in RTR with severe obesity. Significant weight loss was also demonstrated with post-renal transplantation BS.

Differentiation of Cutaneous Metastatic Breast Cancer from Cutaneous Adnexal Tumors Using Wnt9b Polyclonal Antibody Stain

Objective: The histologic diagnosis of cutaneous metastatic breast cancer can be challenging as the differentials can include primary cutaneous glandular neoplasms and metastases from other glandular neoplasms which present very similar on H&amp;E. Many immunohistological markers including GATA3 and CK7 have been employed to screen for primary or metastatic breast cancer cells and because of this, we wanted to develop a stain capable of differentiating these diagnoses quickly and accurately. Methods: We utilized 61 archived dermatopathology laboratory specimens of various benign and malignant cutaneous adnexal and breast tissues for analysis with a polyclonal Wnt9b antibody stain. Results: The average staining in benign categories (cutaneous adnexal and benign breast tissue) as well as metastases from non-breast carcinomas was negative. Among the malignant cutaneous adnexal and metastatic breast tissues, a significant difference was observed in staining as adnexal carcinomas were weakly positive (0.53+) and primarily seen in the outer layer of glandular structures, while metastatic breast tissues were strongly positive (3.63+) (P&lt;0.01). The specificity in both adnexal and metastatic breast tissues was 100% while the sensitivity for adnexal carcinomas was 37% and metastatic breast was 94%. A larger sample size could greatly improve these values. Conclusion: These results demonstrate that Wnt9b has specific staining for cutaneous metastatic breast cell nuclei and could be utilized as a diagnostic to differentiate from cutaneous adnexal tumors in routine dermatopathological applications. Keywords: Metastatic Breast Carcinomas; Cutaneous Adnexal Tumor; Staining; Polyclonal Antibody; Histological Markers

A Proteomics Approach Identifies RREB1 as a Crucial Molecular Target of Imidazo-Pyrazole Treatment in SKMEL-28 Melanoma Cells.

Cutaneous melanoma is the most dangerous and deadly form of human skin malignancy. Despite its rarity, it accounts for a staggering 80% of deaths attributed to cutaneous cancers overall. Moreover, its final stages often exhibit resistance to drug treatments, resulting in unfavorable outcomes. Hence, ensuring access to novel and improved chemotherapeutic agents is imperative for patients grappling with this severe ailment. Pyrazole and its fused systems derived thereof are heteroaromatic moieties widely employed in medicinal chemistry to develop effective drugs for various therapeutic areas, including inflammation, pain, oxidation, pathogens, depression, and fever. In a previous study, we described the biochemical properties of a newly synthesized group of imidazo-pyrazole compounds. In this paper, to improve our knowledge of the pharmacological properties of these molecules, we conduct a differential proteomic analysis on a human melanoma cell line treated with one of these imidazo-pyrazole derivatives. Our results detail the changes to the SKMEL-28 cell line proteome induced by 24, 48, and 72 h of 3e imidazo-pyrazole treatment. Notably, we highlight the down-regulation of the Ras-responsive element binding protein 1 (RREB1), a member of the zinc finger transcription factors family involved in the tumorigenesis of melanoma. RREB1 is a downstream element of the MAPK pathway, and its activation is mediated by ERK1/2 through phosphorylation.

A phase 1/1b study of the IL-2 prodrug WTX-124 in patients with locally advanced or metastatic solid tumors after checkpoint inhibitor therapy: Initial results of the combination dose escalation with pembrolizumab.

2623 Background: High dose IL-2 can produce durable remissions in patients who have progressed on checkpoint inhibitors but is infrequently used due to its life-threatening toxicities such as vascular leak syndrome (VLS). WTX-124 is a half-life extended, masked cytokine (INDUKINE molecule) rationally engineered to release wild type IL-2 in tumors. We previously reported that WTX-124 is clinically active as a monotherapy at doses safely administered in the outpatient setting. Here we update the data and present initial results from the combination dose escalation with pembrolizumab (anti-PD-1; NCT05479812). Methods: In this first-in-human trial, WTX-124 is administered IV Q2W alone or with pembrolizumab 400 mg IV Q6W. Eligible patients are adults with relapsed/refractory solid tumors who have previously received standard of care checkpoint inhibitor regimens. Primary endpoints are safety and ORR; secondary endpoints are PK, PD, immunogenicity, and PFS/OS. The dose escalation is guided by a mTPI-2 study design. Results: As of January 29, 2024, 32 patients have been treated with WTX-124 in five monotherapy dose escalation cohorts (1-18 mg; N=24) and two combination cohorts (3-6 mg; N=8). The most common AEs related to WTX-124 monotherapy were arthralgias, myalgias, fatigue and pruritis. Of ten evaluable patients treated with 12 or 18 mg WTX-124 monotherapy, three had objective responses, including a confirmed CR in a patient with cutaneous squamous cell cancer and unconfirmed PRs in patients with melanoma and gastroesophageal junction cancer. On-treatment tumor biopsies showed evidence of increased lymphocyte activation and PD-L1 expression. Addition of pembrolizumab to 3-6mg WTX-124 did not change the character of AEs observed with WTX-124 monotherapy. Related AEs occurred more frequently for the combination than for 3-6mg WTX-124 monotherapy, but all were mild to moderate in severity (Gr1: 74.2%, Gr2: 25.8%) and there was no increase in the percentage of Gr2 events. No DLTs, related serious AEs, treatment discontinuations due to related toxicities, or occurrences of VLS have been observed in any patient treated to date with either WTX-124 or WTX-124/pembrolizumab. Pembrolizumab did not affect WTX-124 or IL-2 PK. WTX-124 has been escalated to 12 mg IV Q2W, the initial monotherapy dose that produced objective responses, in combination with pembrolizumab. Conclusions: WTX-124 administered as a monotherapy IV Q2W in the outpatient setting is well tolerated and clinically active in patients with relapsed/refractory solid tumors after checkpoint inhibitor therapy. Preliminary results from the ongoing combination dose escalation with pembrolizumab show no new safety signals. Updated data on safety, biomarkers, and preliminary clinical activity for the combination will be presented. Clinical trial information: NCT05479812 .

Biologics Versus JAK Inhibitors. Part I: Cancer Risk. A Narrative Review.

Biological drugs (BD) and Janus kinase inhibitors (JAKi) have revolutionized the treatment of diverse dermatoses. However, there are concerns regarding their safety, especially the risk of cancer and opportunistic infections. Here, we discuss the risk of cancer associated with the BD and JAKi used in dermatology. A narrative review was carried out. All relevant articles evaluating the risk of cancer associated with BD or JAKi and published between January 2010 and February 2024 were selected. Multiple large studies have evaluated the association between BD, JAKi and cancer risk. However, there is a lack of prospective, comparative studies. Overall, patients undergoing BD and JAKi present a cutaneous cancer incidence similar to that in the general population. The drugs more strongly associated with non-skin cancer risk were anti-tumor necrosis factor (anti-TNFs) agents and JAKi (especially tofacitinib and oral ruxolitinib). This risk appears to increase with age, the presence of other factors (such as chronic immunosuppression from previous drugs or other comorbidities), and specific diseases such as rheumatoid arthritis (RA) and myelodysplastic syndrome. Conversely, BD such as interleukin (IL)-17 and IL-23 inhibitors may even reduce the risk of some visceral and hematological malignancies. In patients with dermatological conditions such as psoriasis and atopic dermatitis, the risk of malignancies may be lower than in other subgroups, and probably comparable to the general population. The incidence of cancer in patients undergoing BD or JAKi is generally low. This incidence can be higher in elderly patients with RA or myelodysplastic syndrome, and in those undergoing prolonged therapy with tofacitinib or ruxolitinib (oral), or anti-TNF agents.

The use of a thoracodorsal flap in the surgical treatment of squamous cell skin cancer (case report)

We report a case of successful surgical treatment of a patient with locally advanced cutaneous squamous cell cancer (cSCC) originating from a burn scar. The burn scar cSCC tends to be more aggressive in nature than conventional skin SCC. treatment of patients with cSCC arising from a burn scar is complicated by the fact that the extensive defects formed after tumor removal are almost impossible to close with local tissues. Purpose: to demonstrate the feasibility of performing surgery for locally advanced cSCC using a thoracodorsal flap. Clinical case description. A 70-year old man presented with cSCC of the right shoulder. The patient had experienced a severe burn covering 70 % of his body surface area at a young age. To repair a large skin defect after tumor resection in the right shoulder, a thoracodorsal artery perforator flap was used. there were no complications in the postoperative period. At a follow-up of 7 months, no evidence of tumor recurrence was observed. Conclusion. The thoracodorsal artery perforator flap has contributed to the efficient reconstruction of extensive soft tissue defects in patients with locally advanced cSCC originating from a burn scar.

Photoprotection and dermatological profile of persons with albinism in Plateau state, Nigeria: findings from a collaborative awareness and screening outreach program

Introduction As a result of genetically being deficient of melanin, albinos are particularly susceptible to skin damage from ultraviolet rays leading to photodermatoses such as sunburns, dermatoheliosis, and cutaneous cancers. These negatively affects quality of life and cause premature death. Little is known of the photoprotective measures available to and dermatological profile of persons with albinism in Plateau state, North Central Nigeria. Objective To describe the dermatological profile of albinos in Plateau state, Nigeria, photo exposure levels, photoprotection strategies, and factors associated with presence of photodermatoses. Patients and methods Consenting individuals with albinism attending the sensitization event hosted by the Centre for Albinism Right and Empowerment Network were recruited. Demographic information, occupational history, solar exposure, photoprotective practices, and perceived sun exposure were all documented using semistructured questionnaires. Physical and dermatological examination, dermoscopy, and laboratory investigations were used to make diagnosis. Statistical package for social sciences, version 26, was used to carry out univariate and bivariate analysis. Results While a wide spectrum of skin diseases was observed among the 59 albinos that participated. Photodermatoses were three times more than nonphotodermatoses. The commonest photodermatoses were solar elastosis (55.9%), solar lentigines (44.1%), actinic keratosis (27.1%), and sunburn (25.4%). Skin cancers affected 10.2% of all patients and 16.6% of persons more than or equal to 20 years. Generally, the presence of photodermatoses was associated with age and occupation while actinic keratotic changes specifically was associated with living in rural areas (P=0.035). Despite this, only seven (11.9%) owned sunscreen at the time of study with more than a third (35.2%) being ignorant of existence of sunscreen lotions. Conclusion Continuous multifaceted programs that involve tracking, education, prevention, early detection, and treatment of photodermatoses will be planned to be targeted towards persons with albinism living in Plateau state.

A novel method of assessing intraoperative surgical margins in patients with dermatofibrosarcoma protuberans: A specimen radiography system.

Background Dermatofibrosarcoma protuberans (DFSP) is one of the most challenging cutaneous cancers in surgical clinic practice. Excision with negative margins is essential for effective disease control. However, wide surgical margins and maximal tissue conservation are mutually exclusive. Mohs micrographic surgery conserves tissue but is time-consuming. Thus, we developed a novel specimen radiography system that can be used intraoperatively. Aims To introduce a specimen radiography system for evaluating intraoperative surgical margins in patients with dermatofibrosarcoma protuberans. Methods Since September 2017, we have treated seven biopsy-proven cases of local DFSPs via local excision with surgical margins of 2-4 cm. During operations, the operative specimens were screened using the specimen radiography system. All surgical specimens were pathologically examined intraoperatively. Results Five patients were men and two were women, of median age 36 years. The mean radiographic screening time was 9.7 ± 2.3 min. Radiographically negative margins were confirmed intraoperatively. The minimal margin width ranged from 5.0 to 35.4 mm (mean width 16.9 ± 10.4 mm). The intraoperatively negative radiographic margins were consistent with those revealed by postoperative pathology. The minimal pathological margin width ranged from 4.0 to 34.5 mm (mean 16.6 ± 10.1 mm) and was not significantly different from the intraoperative data. Limitations The sample size was small and positive or negative predictive values were not calculated. Conclusions We introduce a novel method of intraoperative surgical margin assessment for DFSP patients. It may find broad clinical and research applications during oncoplastic surgery.

Apex Nasi: What’s Happening near the Tip of the Nose?

The apex nasi (colloquially, the tip of the nose) is an anatomically complex region that can be divided into 2 parts: the soft tissue/cartilaginous framework of the most anterior-inferior aspect of the nose and the anterior nasal cavity. Detailed knowledge of local anatomy is helpful to characterize pathology and understand patterns of disease spread. Although many lesions of the apex nasi are readily assessed on physical examination, CT and MR imaging can provide important, often complementary, information about this region. CT well demonstrates osseous anatomy, while MR imaging offers increased specificity for certain conditions, given its superior soft-tissue contrast. Regarding specific pathologies of the region, because cutaneous cancers are common and often involve the apex nasi, they will be discussed in detail, along with potential imaging pitfalls such as perineural tumor spread or coexistence with rhinophyma. Certain rare non-neoplastic or developmental lesions, notably nasolabial cysts and pyriform aperture stenosis, are unique to this region. Vascular lesions such as angiosarcoma and venous malformation may involve the apex nasi, as may nasal septal hematoma and abscess, the latter necessitating immediate treatment. Given the high prevalence of rhinoplasty, the imaging appearance of cosmetic nasal implants and selected rare procedural complications is shown.Learning Objective: To describe the anatomic landmarks of the external nose and anterior nasal cavity and to illustrate common and uncommon pathologies in these locations.

Perineural Inflammation as a Novel Feature in Lichen Sclerosus: A Case Series of Histologic and Clinical Features.

Lichen sclerosus (LS) is a frequently encountered inflammatory skin disorder characterized by whitened, atrophic patches that can cause pain and pruritus. The underlying cause of this condition remains unknown. Primarily affecting the genital area, this condition carries an increased risk of developing cutaneous cancers and frequently co-occurs with autoimmune disorders. Our retrospective study aimed to explore histologic features of LS, with a particular focus on a newly established finding and its potential implications. We examined 53 histologic cases of LS collected over 2 years. Experienced pathologists evaluated and reached a consensus on the assignment of histologic features. Patient charts were manually reviewed to gather relevant demographic and clinical data. Statistical analysis was performed using IBM SPSS Statistics (2021). Of the 53 total patients identified as meeting criteria for inclusion in this study, only 8 (15%) were male. Eight cases (15%) demonstrated perineural inflammatory infiltrate. Notably, half of all samples from male patients exhibited perineural inflammatory infiltrate. A statistically significant increase ( P < 0.01) in the presence of dermal plasma cells was identified in cases with perineural inflammation versus cases without this feature. The findings of our study highlight the recurrent nature of perineural inflammation in LS, providing valuable insights into this condition. Furthermore, we observed a notable correlation between perineural inflammation, male patients, and the presence of dermal plasma cells. These discoveries contribute to a better understanding of the underlying mechanisms of LS and suggest avenues for future research into the condition.

Integra® Dermal Regeneration Template in Complex Scalp Reconstruction.

Background/Objectives: The need for surgical reconstruction of scalp defects following the excision of cutaneous skin cancers is an increasingly common procedure. Particular challenges arise when considering options for reconstruction of large defects not amenable to local skin flap coverage. The use of skin grafts poses the risk of donor site morbidity. This paper investigates the emerging use of Integra®, a synthetic acellular dermal regeneration template, as an alternative or adjunct to skin grafting in scalp reconstruction. Methods: The study presents a retrospective analysis of 101 patients who underwent Integra®-based reconstruction of scalp defects. Demographics, procedure details, complications, need for further surgery, and time to healing were evaluated. Results: The overall success rate of the one-stage Integra®-only procedure was 95%, with a minor complication rate of 30.7%. Anticoagulation medication was identified as an independent risk factor for post-operative infection, while previous head and neck radiotherapy and increased defect depth were associated with the requirement for a second-stage skin graft. Conclusions: These findings support the consideration of Integra® as a safe and viable alternative for both partial and full thickness scalp defects in a select cohort of complex highly co-morbid patients, reducing complications and the need for additional procedures.

Development of 5-fluorouracil/etoposide co-loaded electrospun nanofibrous scaffold for localized anti-melanoma therapy.

Nanofibrous scaffolds have emerged as promising candidates for localized drug delivery systems in the treatment of cutaneous cancers. In this study, we prepared an electrospun nanofibrous scaffold incorporating 5-fluorouracil (5-FU) and etoposide (ETP) for chemotherapy targeting melanoma cutaneous cancer. The scaffold was composed of polyvinyl alcohol (PVA) and chitosan (CS), prepared via the electrospinning process and loaded with the chemotherapeutic agents. We conducted relevant physicochemical characterizations, assessed cytotoxicity, and evaluated apoptosis against melanoma A375 cells. The prepared 5-FU/ETP co-loaded PVA/CS scaffold exhibited nanofibers (NFs) with an average diameter of 321 ± 61 nm, defect-free and homogenous morphology. FTIR spectroscopy confirmed successful incorporation of chemotherapeutics into the scaffold. Additionally, the scaffold demonstrated a hydrophilic surface, proper mechanical strength, high porosity, and efficient liquid absorption capacity. Notably, sustained and controlled drug release was observed from the nanofibrous scaffold. Furthermore, the scaffold significantly increased cytotoxicity (95%) and apoptosis (74%) in A375 melanoma cells. Consequently, the prepared 5-FU/ETP co-loaded PVA/CS nanofibrous scaffold holds promise as a valuable system for localized eradication of cutaneous melanoma tumors and mitigation of adverse drug reactions associated with chemotherapy.

Nivolumab + Tacrolimus + Prednisone ± Ipilimumab for Kidney Transplant Recipients With Advanced Cutaneous Cancers.

Cancer-related mortality rates among kidney transplant recipients (KTR) are high, but these patients have largely been excluded from trials of immune checkpoint inhibitors because of immunosuppression and risk of treatment-related allograft loss (TRAL). We conducted a prospective clinical trial testing nivolumab (NIVO) + tacrolimus (TACRO) + prednisone (PRED) ± ipilimumab (IPI) in KTR with advanced cutaneous cancers. Adult KTR with advanced melanoma or basal, cutaneous squamous, or Merkel cell carcinomas were eligible. Immunosuppression was standardized to TACRO (serum trough 2-5 ng/mL) + PRED 5 mg once daily. Patients then received NIVO 480 mg IV once every 4 weeks. The primary composite end point was partial or complete (tumor) response (CR) or stable disease per RECIST v1.1 without allograft loss at 16W. Patients with progressive disease (PD) could receive IPI 1 mg/kg IV + NIVO 3 mg/kg once every 3 weeks × 4 followed by NIVO. Donor-derived cell-free DNA (dd-cfDNA) levels were measured approximately once every 2 weeks as a potential predictor of allograft rejection. Among eight evaluable patients, none met the trial's primary end point. All eight patients experienced PD on NIVO + TACRO + PRED; TRAL occurred in one patient. Six patients then received IPI + NIVO + TACRO + PRED. Best overall responses: two CR (one with TRAL) and four PD (one with TRAL). In total, 7 of 8 pre-NIVO tumor biopsies contained a paucity of infiltrating immune cells. In total, 2 of 5 on-NIVO biopsies demonstrated moderate immune infiltrates; both patients later experienced a CR to IPI + NIVO. In 2 of 3 patients with TRAL, dd-cfDNA elevations occurred 10 and 15 days before increases in serum creatinine. In most KTR with advanced skin cancer, TACRO + PRED provides insufficient allograft protection and compromises immune-mediated tumor regression after administration of NIVO ± IPI. Elevated dd-cfDNA levels can signal treatment-related allograft rejection earlier than rises in serum creatinine.

Effects of Bevacizumab on VEGF/VEGFR and PI3K/AKT Pathways in Cutaneous Ovarian Cancer

Effects of Bevacizumab on VEGF/VEGFR and PI3K/AKT Pathways in Cutaneous Ovarian Cancer