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JAMA Dec 2017Tumor-treating fields (TTFields) is an antimitotic treatment modality that interferes with glioblastoma cell division and organelle assembly by delivering low-intensity... (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
Tumor-treating fields (TTFields) is an antimitotic treatment modality that interferes with glioblastoma cell division and organelle assembly by delivering low-intensity alternating electric fields to the tumor.
OBJECTIVE
To investigate whether TTFields improves progression-free and overall survival of patients with glioblastoma, a fatal disease that commonly recurs at the initial tumor site or in the central nervous system.
DESIGN, SETTING, AND PARTICIPANTS
In this randomized, open-label trial, 695 patients with glioblastoma whose tumor was resected or biopsied and had completed concomitant radiochemotherapy (median time from diagnosis to randomization, 3.8 months) were enrolled at 83 centers (July 2009-2014) and followed up through December 2016. A preliminary report from this trial was published in 2015; this report describes the final analysis.
INTERVENTIONS
Patients were randomized 2:1 to TTFields plus maintenance temozolomide chemotherapy (n = 466) or temozolomide alone (n = 229). The TTFields, consisting of low-intensity, 200 kHz frequency, alternating electric fields, was delivered (≥ 18 hours/d) via 4 transducer arrays on the shaved scalp and connected to a portable device. Temozolomide was administered to both groups (150-200 mg/m2) for 5 days per 28-day cycle (6-12 cycles).
MAIN OUTCOMES AND MEASURES
Progression-free survival (tested at α = .046). The secondary end point was overall survival (tested hierarchically at α = .048). Analyses were performed for the intent-to-treat population. Adverse events were compared by group.
RESULTS
Of the 695 randomized patients (median age, 56 years; IQR, 48-63; 473 men [68%]), 637 (92%) completed the trial. Median progression-free survival from randomization was 6.7 months in the TTFields-temozolomide group and 4.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.52-0.76; P < .001). Median overall survival was 20.9 months in the TTFields-temozolomide group vs 16.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.53-0.76; P < .001). Systemic adverse event frequency was 48% in the TTFields-temozolomide group and 44% in the temozolomide-alone group. Mild to moderate skin toxicity underneath the transducer arrays occurred in 52% of patients who received TTFields-temozolomide vs no patients who received temozolomide alone.
CONCLUSIONS AND RELEVANCE
In the final analysis of this randomized clinical trial of patients with glioblastoma who had received standard radiochemotherapy, the addition of TTFields to maintenance temozolomide chemotherapy vs maintenance temozolomide alone, resulted in statistically significant improvement in progression-free survival and overall survival. These results are consistent with the previous interim analysis.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT00916409.
Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Chemoradiotherapy; Dacarbazine; Disease-Free Survival; Electric Stimulation Therapy; Female; Follow-Up Studies; Glioblastoma; Humans; Maintenance Chemotherapy; Male; Middle Aged; Mitosis; Survival Analysis; Temozolomide
PubMed: 29260225
DOI: 10.1001/jama.2017.18718 -
Molecular Cancer Jul 2020Colorectal cancer (CRC) is the leading cause of cancer-related death worldwide. Exosome shave emerged as crucial regulators of intercellular communication and that...
BACKGROUND
Colorectal cancer (CRC) is the leading cause of cancer-related death worldwide. Exosome shave emerged as crucial regulators of intercellular communication and that abundant Circular RNAs (circRNAs) are enriched within exosomes. CircRNAs are novel members of noncoding RNAs regulating cancer proliferation and progression. However, the function and regulatory mechanism of cancer-derived exosomal circRNAs in CRC remains unclear.
METHODS
CRC cells-derived exosomes were characterized using transmission electron microscopy, nanoparticle tracking analysis (NTA) and western blot. CCK-8, wound healing and transwell assays, and flow cytometry assays were conducted to assess whether exosomes would affect the proliferation, metastasis, and apoptosis of CRC cells, respectively. Moreover, we performed the RNA sequencing and RT-qPCR to identify circRNAs in exosome-stimulated CRC cells. Fluorescence in situ hybridization (FISH) assay was used to detect the cellular distribution of circPACRGL. Bioinformatic analyses (StarBase 2.0) were used to pool the miRNA targets of circPACRGL. Luciferase assays were performed to verify the direct interaction. Finally, flow cytometry was used to detect the differentiation of N1-N2 neutrophils.
RESULTS
Our study identified a novel CRC-derived exosomal circRNA, circPACRGL. We found circPACRGL was significantly upregulated in CRC cells after tumor-derived exosomes addition. Moreover, circPACRGL serves as a sponge for miR-142-3p/miR-506-3p to facilitate the transforming growth factor-β1 (TGF-β1) expression. As a result, circPACRGL promoted CRC cell proliferation, migration and invasion, as well as differentiation of N1 to N2 neutrophils via miR-142-3p/miR-506-3p-TGF-β1 axis.
CONCLUSION
Our study, the first to reveal that cancer-derived exosomal circPACRGL plays an oncogenic role in CRC proliferation and metastasis, providing mechanistic insights into the roles of circRNAs in CRC progression and a valuable marker for CRC treatment.
Topics: Animals; Apoptosis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Colorectal Neoplasms; Disease Models, Animal; Exosomes; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; MicroRNAs; Models, Biological; RNA Interference; RNA, Circular; Signal Transduction; Transforming Growth Factor beta1; Tumor Microenvironment; Xenograft Model Antitumor Assays
PubMed: 32713345
DOI: 10.1186/s12943-020-01235-0 -
American Family Physician Sep 2020Keratinocyte carcinoma, traditionally referred to as nonmelanoma skin cancer, includes basal cell and cutaneous squamous cell carcinoma and is the most common skin... (Review)
Review
Keratinocyte carcinoma, traditionally referred to as nonmelanoma skin cancer, includes basal cell and cutaneous squamous cell carcinoma and is the most common skin cancer malignancy found in humans. The U.S. Preventive Services Task Force recommends counseling about minimizing exposure to ultraviolet radiation for people aged six months to 24 years with fair skin types to decrease their risk of skin cancer. Routine screening for skin cancer is controversial. The U.S. Preventive Services Task Force concludes that current evidence is insufficient to assess the balance of benefits and harms of a routine whole-body skin examination to screen for skin cancer. Basal cell carcinoma commonly appears as a shiny, pearly papule with a smooth surface, rolled borders, and arborizing telangiectatic surface vessels. Cutaneous squamous cell carcinoma commonly appears as a firm, smooth, or hyperkeratotic papule or plaque, and may have central ulceration. Initial tissue sampling for diagnosis is a shave technique if the lesion is raised, or a punch biopsy of the most abnormal-appearing area of skin. High-risk factors for recurrence and metastasis include prior tumors, ill-defined borders, aggressive histologic patterns, and perineural invasion. Mohs micrographic surgery has the lowest recurrence rate among treatments but is best considered for large, high-risk tumors or tumors in sensitive anatomic locations. Smaller, lower-risk tumors are treated with surgical excision, electrodesiccation and curettage, or cryotherapy. Topical imiquimod and fluorouracil are also treatment options for superficial basal cell carcinoma and squamous cell carcinoma in situ. There are no clear guidelines for follow up after an index keratinocyte carcinoma, but monitoring for recurrence is important because the five-year risk of subsequent skin cancer is 41%. After more than one diagnosis, the five-year risk increases to 82%.
Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Family Practice; Humans; Mohs Surgery; Practice Patterns, Physicians'; Skin Neoplasms
PubMed: 32931212
DOI: No ID Found -
Indian Dermatology Online Journal 2018Nail biopsy is a procedure not routinely resorted to; but when indicated, it is often the only clue left for diagnosis. At such times, it pays to be conversant with it.... (Review)
Review
Nail biopsy is a procedure not routinely resorted to; but when indicated, it is often the only clue left for diagnosis. At such times, it pays to be conversant with it. It is an investigation that not only provides etiologic, diagnostic, and prognostic information but also aids in understanding the pathogenesis of nail diseases. It can be of therapeutic value, especially with respect to nail tumors. This article compiles the procedural techniques for nail biopsy of various types and attempts to summarize the evidence available in the literature. The objective of nail biopsy is to clinch a precise diagnosis of nail pathology with a simple and safe surgical procedure, avoiding pain or permanent nail damage. Patient selection is of utmost importance, wherein, the patient does not have typical skin lesions, yields inadequate information on routine nail investigations, and has no peripheral vascular compromise. The patient needs to be explained about the risks associated, the expected functional handicap, the time required for regrowth, a possibility of permanent nail dystrophy, and a possibility of not achieving a diagnosis even after the biopsy. Techniques and types of various nail biopsies are being discussed in this article. The specimen could be collected as an excision biopsy, punch biopsy, shave biopsy, or longitudinal biopsy. The trick lies in choosing the appropriate area for biopsy. Various biopsy types discussed in this article include nail plate biopsy (easiest and least scarring); nail bed biopsy (elliptical excision or punch); nail matrix biopsy (elliptical excision, punch excision (≤3 mm) or tangential/shave excision); and nail fold biopsy. Complications reported along with means to minimize them are also discussed.
PubMed: 29441291
DOI: 10.4103/idoj.IDOJ_268_17 -
Theranostics 2020V-domain immunoglobulin suppressor of T cell activation (VISTA) is a novel inhibitory immune checkpoint molecule. Vsir mice have exacerbated psoriasis-like skin...
V-domain immunoglobulin suppressor of T cell activation (VISTA) is a novel inhibitory immune checkpoint molecule. Vsir mice have exacerbated psoriasis-like skin inflammation. The immune cell subsets involved in inflammation in Vsir psoriatic mice are largely unknown. We have used scRNA-seq as an unbiased profiling strategy to study the heterogeneity of immune cells at a single cell level in the skin of Vsir psoriatic mice. In the present study, the right ear and shaved back skin of wild type and Vsir mice were treated with IMQ for 5 consecutive days to induce psoriasis-like dermatitis. Then, the single-cell RNA sequencing analysis of mouse back skin lesions was performed using 10 × Genomics technique. We identified 12 major cell subtypes among 23,258 cells. The major populations of the skin cells included macrophages, dendritic cells and fibroblasts. Macrophages constituted the main immune cell population in the WT (61.29%) and Vsir groups (77.7%). It should be noted that DCs and fibroblasts were expanded in the Vsir psoriatic mice. Furthermore, the gene expression signatures were assessed. We observed that Hspb1 and Cebpb were significantly upregulated in the Vsir psoriatic mice. Differential gene expression and gene ontology enrichment analyses revealed specific gene expression patterns distinguishing these subsets and uncovered putative functions of each cell type. Date analysis resulted in the discovery of a number of novel psoriasis-associated genes in Vsir mice. We present a comprehensive single-cell landscape of the skin immune cells in Vsir psoriatic mice. These unprecedented data uncovered the transcriptional landscape and phenotypic heterogeneity of skin macrophages in psoriasis and identified their gene expression signature suggesting specialized functions in Vsir mice. Our findings will open novel opportunities to investigate the role of VISTA in driving psoriasis.
Topics: Animals; Dendritic Cells; Disease Models, Animal; Female; Fibroblasts; Humans; Imiquimod; Macrophages; Membrane Proteins; Mice; Mice, Knockout; Psoriasis; RNA-Seq; Single-Cell Analysis; Skin; Transcription, Genetic; Transcriptome
PubMed: 32929361
DOI: 10.7150/thno.45614 -
Annals of Surgical Oncology Oct 2021Melanoma is the most lethal skin cancer. Excision biopsy is generally recommended for clinically suspicious pigmented lesions; however, a proportion of cutaneous... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Melanoma is the most lethal skin cancer. Excision biopsy is generally recommended for clinically suspicious pigmented lesions; however, a proportion of cutaneous melanomas are diagnosed by shave biopsy. A systematic review was undertaken to investigate the impact of shave biopsy on tumor staging, treatment recommendations, and prognosis.
METHODOLOGY
The MEDLINE, Embase, and Cochrane Library databases were searched for relevant articles. Data on deep margin status on shave biopsy, tumor upstaging, and additional treatments on wide local excision (WLE), disease recurrence, and survival effect were analyzed across studies.
RESULTS
Fourteen articles from 2010 to 2020 were included. In total, 3713 patients had melanoma diagnosed on shave biopsy. Meta-analysis revealed a positive deep margin in 42.9% of shave biopsies. Following WLE, change in tumor stage was reported in 7.7% of patients. Additional treatment was recommended for 2.3% of patients in the form of either further WLE and/or sentinel lymph node biopsy. There was high heterogeneity across studies in all outcomes. Four studies reported survival, while no studies found any significant difference in disease-free or overall survival between shave biopsy and other biopsy modalities.
CONCLUSIONS
Just over 40% of melanomas diagnosed on shave biopsy report a positive deep margin; however, this translated into a change in tumor stage or treatment recommendations in relatively few patients (7.7% and 2.3%, respectively), with no impact on local recurrence or survival among the studies analyzed.
Topics: Biopsy; Humans; Melanoma; Neoplasm Staging; Retrospective Studies; Sentinel Lymph Node Biopsy; Skin; Skin Neoplasms
PubMed: 33782802
DOI: 10.1245/s10434-021-09866-3 -
Anais Brasileiros de Dermatologia 2016Pitted keratolysis is a skin disorder that affects the stratum corneum of the plantar surface and is caused by Gram-positive bacteria. A 30-year-old male presented with...
Pitted keratolysis is a skin disorder that affects the stratum corneum of the plantar surface and is caused by Gram-positive bacteria. A 30-year-old male presented with small punched-out lesions on the plantar surface. A superficial shaving was carried out for scanning electron microscopy. Hypokeratosis was noted on the plantar skin and in the acrosyringium, where the normal elimination of corneocytes was not seen. At higher magnification (x 3,500) bacteria were easily found on the surface and the described transversal bacterial septation was observed.
Topics: Adult; Corynebacterium Infections; Epidermis; Foot Dermatoses; Humans; Keratosis; Male; Microscopy, Electron, Scanning; Skin Diseases, Bacterial
PubMed: 26982791
DOI: 10.1590/abd1806-4841.20164096 -
Journal of Clinical Medicine Mar 2024: Maximizing survival for patients with primary cutaneous melanomas (melanomas) depends on an early diagnosis and appropriate management. Several new drugs have been...
: Maximizing survival for patients with primary cutaneous melanomas (melanomas) depends on an early diagnosis and appropriate management. Several new drugs have been shown to improve survival in high-risk melanoma patients. Despite well-documented guidelines, many patients do not receive optimal management, particularly when considering patient age. : to provide an update on melanoma management from the time of the decision to biopsy a suspicious skin lesion. : We reviewed melanoma-management research published between 2018 and 2023 and identified where such findings impact and update the management of confirmed melanomas. Pubmed, Google Scholar, Ovid and Cochrane Library were used as search tools. : We identified 81 publications since 2017 that have changed melanoma management; 11 in 2018, 12 in 2019, 10 in 2020, 12 in 2021, 17 in 2022 and 18 in 2023. : Delayed or inaccurate diagnosis is more likely to occur when a partial shave or punch biopsy is used to obtain the histopathology. Wherever feasible, a local excision with a narrow margin should be the biopsy method of choice for a suspected melanoma. The Breslow thickness of the melanoma remains the single most important predictor of outcome, followed by patient age and then ulceration. The BAUSSS biomarker, (Breslow thickness, Age, Ulceration, Subtype, Sex and Site) provides a more accurate method of determining mortality risk than older currently employed approaches, including sentinel lymph node biopsy. Patients with metastatic melanomas and/or nodal disease should be considered for adjuvant drug therapy (ADT). Further, high-risk melanoma patients are increasingly considered for ADT, even without disease spread. Invasive melanomas less than 1 mm thick are usually managed with a radial excision margin of 10 mms of normal skin. If the thickness is 1 to 2 mm, select a radial margin of 10 to 20 mm. When the Breslow thickness is over 2 mm, a 20 mm clinical margin is usually undertaken. In situ melanomas are usually managed with a 5 to 10 mm margin or Mohs margin control surgery. Such wide excisions around a given melanoma is the only surgery that can be regarded as therapeutic and required. Patients who have had one melanoma are at increased risk of another melanoma. Ideal ongoing management includes regular lifelong skin checks. Total body photography should be considered if the patient has many naevi, especially when atypical/dysplastic naevi are identified. Targeted approaches to improve occupational or lifestyle exposure to ultraviolet light are important. Management also needs to include the consideration of vitamin D supplementary therapy.
PubMed: 38541831
DOI: 10.3390/jcm13061607