Malignant Research Articles

Disruption of the ZFP574–THAP12 complex suppresses B cell malignancies in mice

Disruption of the ZFP574–THAP12 complex suppresses B cell malignancies in mice

Standardizing Retrospective Observational Research in Cutaneous Squamous Cell Carcinoma: Expert Panel Guidelines from ITSCC.

Cutaneous squamous cell carcinoma (CSCC) is the second most common malignant disease in the US. Although it typically carries a good prognosis, a subset of CSCCs are highly aggressive, carrying regional and distant metastatic potential. Due to its high incidence, this aggressive subset is responsible for considerable mortality, with an overall annual mortality estimated to equal or even surpass melanoma. Despite this morbidity, CSCC is excluded from national cancer registries, making it difficult to study its epidemiology and outcomes. Therefore, the bulk of the CSCC literature is composed of single-center and multi-institutional retrospective cohort analyses. Given variations in reporting measures and analyses in these studies, interpretability between studies and the ability to pool results are limited. To define standardized reporting measures for retrospective CSCC studies. An expert panel was convened to determine standardized guidelines for recording and analyzing retrospective CSCC data. A total of 13 dermatologists and dermatologic surgeons with more than 5 years of posttraining experience and considerable experience with performing CSCC outcomes research were recruited to the panel. Consensus recommendations were achieved for CSCC retrospective study reporting measures, definitions, and analyses. The recommendations in this report present the potential to standardize future CSCC retrospective studies. With such standardization, future work may have greater interstudy interpretability and allow for pooled analyses.

MicroRNAs as Bile-based biomarkers in pancreaticobiliary cancers (MIRABILE): a cohort study.

Biliary obstruction can be due to both malignant and benign pancreaticobiliary disease. Currently, there are no biomarkers that can accurately help make this distinction. MicroRNAs (miRNAs) are stable molecules in tissue and biofluids that are commonly deregulated in cancer. The MIRABILE study aimed to identify miRNAs in bile that can differentiate malignant from benign pancreaticobiliary disease. There were 111 patients recruited prospectively at endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC) for obstructive jaundice, and bile was aspirated for cell-free RNA (cfRNA) extraction and analysis. In a discovery cohort of 78 patients (27 with pancreatic ductal adenocarcinoma (PDAC), 14 cholangiocarcinoma (CCA), 37 benign disease), cfRNA was subjected to small-RNA sequencing. LASSO regression was used to define bile miRNA signatures, and NormFinder to identify endogenous controls. In a second cohort of 87 patients (34 PDAC, 14 CCA, 39 benign disease), RT-qPCR was used for validation. LASSO regression identified 14 differentially-expressed bile miRNAs of which 6 were selected for validation. When comparing malignant and benign pancreaticobiliary disease, bile miR-340 and miR-182 were validated and significantly differentially expressed (P<0.05 and P<0.001, respectively). This generated an AUC of 0.79 (95%CI 0.70-0.88, sensitivity 65%; specificity 82%) in predicting malignant disease. Bile collected during biliary drainage contains miRNAs able to differentiate benign from malignant pancreaticobiliary diseases in patients with obstructive jaundice. These bile miRNAs have the potential to increase diagnostic accuracy.

3D bioprinting of an in vitro hepatoma microenvironment model: Establishment, evaluation, and anticancer drug testing

Tumor behavior, including its response to treatments, is influenced by interactions between mesenchymal and malignant cells, as well as their spatial arrangement. To study tumor biology and evaluate anticancer drugs, accurate 3D tumor models are essential. Here, we developed an in vitro biomimetic hepatoma microenvironment model by combining an extracellular matrix (3DM-7721). Initially, the internal grid structure, composed of 10/6 % GelMA/gelatin loaded with SMMC-7721 cells, was printed using 3D bioprinting. The external component consisted of fibroblasts and human umbilical vein endothelial cells loaded with 10/3 % GelMA/gelatin. A control model (3DP-7721) lacked external cell loading. GelMA/gelatin hydrogels provided robust structural support and biocompatibility. The SMMC-7721 cells in the 3DM-7721 model exhibit superior tumor-associated gene expression and proliferation characteristics when compared to the 3DP-7721 model. Furthermore, the 3DM-7721 type exhibited increased resistance to anticancer agents. SMMC-7721 cells in the 3DM-7721 model exhibit significant tumorigenicity in nude mice. The 3DM-7721 model group showed pathological characteristics of malignant tumors, with a high degree of deterioration, and a significant positive correlation between malignant tumor-related gene pathways. This high-fidelity 3DM-7721 tumor microenvironment model is invaluable for studying tumor progression, devising effective treatment strategies, and discovering drugs. Statement of significance1.A hepatoma microenvironment model (3DM-7721) incorporating an extracellular matrix that is designed to establish solid tumor models in vitro.2.This model contains a 3D-printed internal tumor component of liver cancer cells loaded with 10/6 % gelatin methacrylate (GelMA)/gelatin (the 3DP-7721 model) and an external extracellular-matrix component of fibroblasts and human umbilical vein endothelial cells loaded with 10/3 % GelMA/gelatin.3.The 3DM-7721 model outperforms the 3DP-7721 model in terms of the SMMC-7721 cell proliferation characteristics and tumorigenicity, tumor-related gene expression, anticancer drug resistance, and malignant tumor characteristics.

China clinical practice guideline for stage Ⅳ primary lung cancer (2024 edition)

Primary lung cancer (abbreviated as lung cancer) stands as the most prevalent malignant disease and the leading cause of cancer-related death in China, with an estimated 106.06×104 incident cases and 73.33×104 deaths in 2022. Due to the absence of effective early screening methods, most patients with lung cancer in China are in stage Ⅳ when diagnosed. Multi-disciplinary treatment based on systemic therapy is the treatment principle for patients with stage Ⅳ lung cancer. Chemotherapy remains the cornerstone, but its effectiveness is still unsatisfactory. In recent years, with the rapid development of molecular targeted therapy and immunotherapy, the treatment concept for stage Ⅳ lung cancer has been continually evolving, leading to significant improvements in patient treatment outcomes. To ensure timely updates on the global progress in the treatment of stage Ⅳ lung cancer and further improve the level of standardized diagnosis and treatment of stage Ⅳ lung cancer in China, Medical Oncology Branch of China International Exchange and Promotive Association for Medical and Health Care and Chinese Association for Clinical Oncologists organized experts to compile "China clinical practice guideline for stage Ⅳ primary lung cancer (2024 edition)". This guideline systematically and comprehensively updates epidemiological data, TNM staging, new drugs, treatment regimens, and new indications approved by China National Medical Products Administration before June 30, 2024, etc. Based on the " Clinical practice guideline for stage Ⅳ primary lung cancer in China(2021 version)" and the " Clinical practice guideline for stage Ⅳ lung cancer in China (2023 edition)." This guideline incorporates recommendation levels for therapeutic drugs and treatment flowcharts for stage Ⅳ lung cancer. The guideline covers common clinical issues and corresponding guidance in the diagnosis and treatment process of stage Ⅳ lung cancer. The guideline aims to guide the clinical practice of stage Ⅳ lung cancer, comprehensively improve the standardized diagnosis and treatment level in China, prolong the survival time of patients with stage Ⅳ lung cancer, and improve patients' quality of life.

Comprehensive analysis of endoplasmic reticulum stress related signature in head and neck squamous carcinoma

Head and neck squamous carcinoma (HNSC) is a prevalent malignant disease, with the majority of patients being diagnosed at an advanced stage. Endoplasmic reticulum stress (ERS) is considered to be a process that promotes tumorigenesis and impacts the tumor microenvironment (TME) in various cancers. The study aims to investigate the predictive value of ERS in HNSC and explore the correlation between ERS-related genes and TME. A series of bioinformatics analyses were carried out based on mRNA and scRNA-seq data from the TCGA and GEO databases. We conducted RT-qPCR and western blot to validate the signature, and performed cell functional experiments to investigate the in vitro biological functions of the gene. We identified 63 ERS-related genes that were associated with outcome and stage in HNSC. A three-gene signature (ATF6, TRIB3, and UBXN6) was developed, which presents predictive value in the prognosis and immunotherapy response of HNSC patients. The high-risk group exhibited a worse prognosis but may benefit from immunotherapy. Furthermore, there was a significant correlation between the signature and immune infiltration. In the high-risk group, fibroblasts were more active in intercellular communication, and more T cells were observed at the end of the sequential phase. The genes in the ERS-related signature were overexpressed in HNSC cells, and the knockdown of TRIB3 significantly inhibited cell proliferation and migration. This study established a novel ERS-related signature that has potential implications for HNSC therapy and the understanding of TME.

Class Ⅱ ferroptosis inducers are a novel therapeutic approach for t(4;14)-positive multiple myeloma.

Multiple myeloma (MM) is a clonal plasma cell malignancy characterized by genetic heterogeneity. The cytogenetic abnormality t(4;14) strongly predicts poor outcome in MM patients even in the era of novel drugs. Ferroptosis is a new approach to antitumor therapy, but the relationship between ferroptosis and MM cytogenetic abnormalities remains largely unclear. Here, we show that t(4;14)-positive but not t(4;14)-negative MM cells are susceptible to class II ferroptosis inducers (FINs) in a preclinical setting, which is dependent on the significant upregulation of the MM SET domain-containing protein (MMSET). Mechanistically, MMSET upregulates acyl-CoA synthetase long-chain family member 4 (ACSL4) transcription by binding to its promoter region, leading to increased polyunsaturated fatty acid (PUFA) levels and enhanced sensitivity of t(4;14)-positive MM to ferroptosis. Supplementation of PUFAs efficiently restores ferroptosis susceptibility of t(4;14)-negative MM. In addition, combination treatment of class II FINs and bortezomib in t(4;14)-positive MM attenuates cellular glutathione and induces both apoptosis and ferroptosis levels by inhibiting the increase of solute carrier family 7 member 11, demonstrating synergistic anti-tumor activity in vitro and in a xenograft model. Taken together, our findings suggest that targeting ferroptosis with class II FINs is a novel and promising therapeutic approach to improve the outcome of t(4;14)-positive MM.

Enhancement of complement-dependent cytotoxicity by linking factor-H derived short consensus repeats 19-20 to CD20 antibodies

Antibody-mediated complement-dependent cytotoxicity (CDC) on malignant cells is regulated by several complement control proteins, including the inhibitory complement factor H (fH). fH consists of 20 short consensus repeat elements (SCRs) with specific functional domains. Previous research revealed that the fH-derived SCRs 19–20 (SCR1920) can displace full-length fH on the surface of chronic lymphocytic leukemia (CLL) cells, which sensitizes CLL cells for e.g. CD20-targeting therapeutic monoclonal antibody (mAb) induced CDC. Therefore, we constructed lentiviral vectors for the generation of cell lines that stably produce mAb-SCR-fusion variants starting from the clinically approved parental mAbs rituximab, obinutuzumab and ofatumumab, respectively. Flow-cytometry revealed that the modification of the mAbs by the SCRs does not impair the binding to CD20. Increased in vitro lysis potency compared to their parental mAbs was corroborated by showing specific and dose dependent target cell elimination by CDC when compared to their parental mAbs. Lysis of CLL cells was not affected by the depletion of NK cells, suggesting that antibody-dependent cellular cytotoxicity plays a minor role in this context. Overall, this study emphasizes the crucial role of CDC in the elimination of CLL cells by mAbs and introduces a novel approach for enhancing CDC by directly fusing fH SCR1920 with mAbs.

Investigating the impact of SMAD2 and SMAD4 downregulation in colorectal cancer and their correlation with immune markers, prognosis, and drug resistance and sensitivity.

While many genes linked to colorectal cancer (CRC) contribute to cancer development, a thorough investigation is needed to explore crucial hub genes yet to be fully studied. A pivotal pathway in CRC is transforming growth factor-beta (TGF-β). This study aimed to assess SMAD2 and SMAD4 gene expression from this pathway. Counted data from the Cancer Genome Atlas (TCGA) were examined, comparing 483 tumor and 41 normal samples. Using clinical data, genes impacting overall survival (OS) were evaluated. GSE39582 was employed to confirmed the levels of genes in CRC compared to the normal samples. Additionally, employing unhealthy samples and the RT-qPCR means our outcomes was validated. Finally, PharmacoGx information were utilized to connect the levels of potential genes to drug tolerance and susceptibility. Our findings showed SMAD2 and SMAD4 levels in TGF-β signaling were more significant than other pathway genes. Our findings indicated that the protein levels of these genes were lower in malignant tissues than in healthy tissues. Results revealed a significant correlation between low levels of SMAD2 and unfavorable OS in CRC individuals. RT-qPCR results demonstrated decreased expressions of both SMAD2 and SMAD4 in cancer tissues compared to elevated levels in adjacent normal samples. Our results showed significant association between selected genes and immune cell infiltration markers such as CD8+, and B-cells. Our results indicated a potential association among the levels of SMAD2 and SMAD4 genes and tolerance and susceptibility to Nilotinib and Panobinostat drugs. Reduced expression of SMAD2 and SMAD4 may be pivotal in CRC progression, impacting downstream genes unrelated to patient OS. These findings suggest a potential role for SMAD2 and SMAD4 as predictive markers for drug response in CRC patients.

Downregulation of tRF-Cys-GCA-029 by hyperglycemia promotes tumorigenesis and glycolysis of diabetic breast cancer through upregulating PRKCG translation

BackgroundDiabetes mellitus (DM) affects up to one-third of breast cancer (BC) patients. Patients with co-existing BC and DM (BC-DM) have worsened BC prognosis. Nevertheless, the molecular mechanisms orchestrating BC-DM prognosis remain poorly understood. tRNA-derived fragments (tRFs) have been shown to regulate cancer progression. However, the biological role of tRFs in BC-DM has not been explored.MethodstRF levels in tumor tissues and cells were detected by tRF sequencing and qRT-PCR. The effects of tRF on BC cell malignancy were assessed under euglycemic and hyperglycemic conditions in vitro. Metabolic changes were assessed by lactate, pyruvate, and extracellular acidification rate (ECAR) assays. Diabetic animal model was used to evaluate the impacts of tRF on BC tumor growth. RNA-sequencing (RNA-seq), qRT-PCR, Western blot, polysome profiling, luciferase reporter assay, and rescue experiments were performed to explore the regulatory mechanisms of tRF in BC-DM.ResultsWe identified that tRF-Cys-GCA-029 was downregulated in BC-DM tissues and under hyperglycemia conditions in BC cells. Functionally, downregulation of tRF-Cys-GCA-029 promoted BC cell proliferation and migration in a glucose level-dependent manner. tRF-Cys-GCA-029 knockdown also enhanced glycolysis metabolism in BC cells, indicated by increasing lactate/pyruvate production and ECAR levels. Notably, injection of tRF-Cys-GCA-029 mimic significantly suppressed BC tumor growth in diabetic-mice. Mechanistically, tRF-Cys-GCA-029 regulated BC cell malignancy and glycolysis via interacting with PRKCG in two ways: binding to the coding sequence (CDS) of PRKCG mRNA to regulate its transcription and altering polysomal PRKCG mRNA expression to modify its translation.ConclusionsHyperglycemia-downregulated tRF-Cys-GCA-029 enhances the malignancy and glycolysis of BC cells. tRF-Cys-GCA-029-PRKCG-glycolysis axis may be a potential therapeutic target against BC-DM.Graphical

Research on the mean maximum Young’s modulus value as a new diagnostic parameter for prostate cancer

Ultrasound-based shear wave elastography (SWE) can non-invasively assess prostate tissue stiffness for the diagnosis of prostate cancer (PCa). So far, there is no widely recognized standard for the detection process and calculation method of Young’s modulus value in transrectal SWE ultrasound imaging (TSWEUI). In our study, the mean maximum Young’s modulus value (m-Emax) of the maximum cross-section of prostate is obtained by calculating the mean of 12 measured Emax in the four quadrants. This retrospective study included 209 suspected malignant prostate disease patients with pathological results in our hospital. Among the 209 patients, 75 patients completed TSWEUI, and 63 of the 75 patients completed magnetic resonance imaging (MRI). The area under the receiver operating characteristic (ROC) curve (AUC) of 75 patients for m-Emax was 0.754. The prostate volume, prostate-specific antigen, and m-Emax were used to develop a nomogram (AUC = 0.868). The nomogram could effectively predict the probability of PCa, thereby reducing the needle biopsy rate for diagnosing PCa. The AUC of 63 patients was not statistically different between m-Emax (AUC = 0.717) and MRI (AUC = 0.787) (P = 0.361). These indicate that m-Emax can be used as an innovative parameter in TSWEUI to diagnosis PCa. TSWEUI is more cost-effective than MRI in diagnosing PCa.

Co-administration of either curcumin or resveratrol with cisplatin treatment decreases hepatotoxicity in rats via anti-inflammatory and oxidative stress-apoptotic pathways

Background Cisplatin (CIS) is a broad-spectrum anticancer drug, with cytotoxic effects on either malignant or normal cells. We aimed to evaluate the hepatotoxicity in rats caused by CIS and its amelioration by the co-administration of either curcumin or resveratrol. Materials and Methods Forty adult male rats divided into four equal groups: (control group): rats were given a saline solution (0.9%) once intraperitoneally, daily for the next 28 days; (cisplatin group): rats were given a daily oral dose of saline solution (0.9%) for 28 days after receiving a single dose of cisplatin (3.3 mg/kg) intraperitoneally for three successive days; (CIS plus curcumin/resveratrol groups): rats received the same previous dose of cisplatin (3.3 mg/kg) daily for three successive days followed by oral administration of either curcumin/resveratrol solution at a dose of (20 mg/kg) or (10 mg/kg) consequently daily for 28 days. Different laboratory tests (ALT, AST, ALP, bilirubin, oxidative stress markers) and light microscopic investigations were done. Results Administration of CIS resulted in hepatotoxicity in the form of increased liver enzymes, oxidative stress markers; degenerative and apoptotic changes, the co-administration of CIS with either curcumin or resveratrol improved hepatotoxicity through improved microscopic structural changes, reduction in liver enzymes activity, decreased oxidative stress markers, improved degenerative, and apoptotic changes in liver tissues. Conclusion Co-administration of either curcumin or resveratrol with cisplatin treatment could ameliorate hepatotoxicity caused by cisplatin in rats via anti-inflammatory and oxidative stress-apoptotic pathways.

Nanoemulsions in Skin Cancer Therapy: A Promising Frontier.

Skin cancer, a global burden for particularly white people, is classified as various histopathological types, including malignant melanoma, basal and squamous cell carcinoma, on the basis of affected different skin layers. Clinical adjuvant therapy (electro-chemotherapy, radio- and immuno therapy), surgical techniques (Cryosurgery, laser treatment, dermabrasion, Moh's micrographic surgery), photodynamic treatment and theranostic approaches are confined only for the treatment of serious health issues. Therefore, nanotechnology based approaches, especially nanoemulsion, a non-spontaneous, transparent or translucent, kinetically stable nanostructured (1-1000nm) colloidal dispersion (comprised of oil, water and surfactant/cosurfactant), are being popularised as a potential topical nanocarrier to deliver BCS class II and IV anti-neoplastic drugs attributing to its capacity for both active and passive tumor targeting in controlled or sustained manner and improving bioavailability via enhancing permeabilityretention effect with minimal adverse effects. Numerous research on nanoemulsion for the treatment of both melanoma and non-melanoma skin cancer is only limited to preclinical stages as several physiological variables reduce the effectiveness of nanoemulsion via restricting topical penetration.

Current surgical approach: Extracranial malignant germ cell tumors.

Germ cell tumors (GCT) are a complex, heterogeneous collection of tumors that may present in either gonadal or extragonadal sites. They consist of a variety of benign and malignant histologies that can occur at several locations throughout the body. An important component of treatment is surgical resection, and while the key components of resection are site specific, the universal goals of GCT resection include the complete resection of tumor without violating the tumor capsule, while preserving function of surrounding organs, minimizing morbidity, and assessing for regional spread.

Leucine rich α2 glycoprotein 1 derived from malignant pleural mesothelioma cells facilitates macrophage M2 phenotypes

Background: Macrophages constitute the main part of infiltrating immune cells in Malignant pleural mesothelioma (MPM) and abnormally high ratios of M2 macrophages are present in both pleural effusion and tissue samples of MPM patients. Whether MPM cells affect formation of M2 macrophages is poorly understood. In this study, we focused on identification of MPM-cells-derived soluble factors with M2-promoting effects. Methods: Media of malignant pleural mesothelioma cells were collected and soluble factors affecting macrophages were analyzed by mass spectrometry. TGF-β receptor inhibitor SB431542 was used as the entry point to explore the downstream mechanism of action by qRT-PCR, WB and immunofluorescence. Results: The serum-free culture media collected from the human MPM cells Meso1 and Meso2 significantly enhanced expression of the M2 signature molecules including IL-10, TGF-β and CD206 in the human macrophages THP-1, while the culture medium of the human MPM cells H2452 did not show such M2-promoting effects. Analysis of proteins by mass spectrometry and ELISA suggested that Leucine rich α2 glycoprotein 1(LRG1) was a potential candidate. LRG1 time- and dose-dependently increased expression of the M2 signature molecules, confirming its M2-promoting effects. Furthermore, LRG1’s M2-promoting effects were reduced by the TGF-β receptor inhibitor SB431542, and LRG1 increased phosphorylation of Smad2, indicating that M2-promoting effects of LRG1 were via the TGF-β receptor/Smad2 signaling pathway. Conclusions: Our results provide a potential M2-promoting new member, LRG1, which contributes to the immune escape of MPM via the TGF-β receptor/Smad2 signaling pathway.

The use of self-expanding metallic stents in the management of benign colonic obstruction: a systematic review and meta-analysis

IntroductionPatients presenting with large bowel obstruction (LBO) frequently undergo emergency surgery that is associated with significant morbidity. In malignant LBO, endoscopic approaches with placement is a self-expanding metal stent (SEMS), have been proposed to prevent emergency surgery and act as a bridge to an elective procedure—with the intention of avoiding a stoma and reducing morbidity. This systematic review aims to assess the quality and outcomes of data available on the use of SEMS in benign causes of colonic obstruction.MethodsThis systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the protocol was registered on Prospero (ID: CRD42021239363). PUBMED, MEDLINE, HMIC, CINAHL, AMED, EMBASE, APA and Cochrane databases were searched. Studies were assessed for quality utilising the MINORS criteria. Pooled odds ratios with 95% confidence intervals (95% CI) were calculated using random effects models.ResultsSixteen studies were included for analysis. 300 patients were included with an average age of 68, and a male predominance of 57%. The quality of the papers included were at risk of bias. The pooled rate of technical success of procedure was 94.4% (95% CI 90.5–96.8%) The pooled rate of clinical success was 77.6% (95% CI: 66.6–85.7%). Adverse effects were low, with perforation 8.8% (4.5–16.6%), recurrence 26.5% (17.2–38.5%) and stent migration 22.5% (14.1–33.8%).DiscussionThis systematic review demonstrated that SEMS for benign colonic obstruction can be a safe and successful procedure. The utilisation of SEMS in malignant disease as a bridge to surgery has been well documented. Whilst the limitations of the data interpreted are appreciated, we postulate that SEMS could be utilised to decompress patients acutely and allow pre-operative optimisation, leading to a more elective surgery with less subsequent morbidity.

Research progresses of imaging studies on preoperative prediction of microvascular invasion of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer, accounting for approximately 90% of liver cancer cases. It currently ranks as the fifth most prevalent cancer worldwide and represents the third leading cause of cancer-related mortality. As a malignant disease with surgical resection and ablative therapy being the sole curative options available, it is disheartening that most HCC patients who undergo liver resection experience relapse within five years. Microvascular invasion (MVI), defined as the presence of micrometastatic HCC emboli within liver vessels, serves as an important histopathological feature and indicative factor for both disease-free survival and overall survival in HCC patients. Therefore, achieving accurate preoperative noninvasive prediction of MVI holds vital significance in selecting appropriate clinical treatments and improving patient prognosis. Currently, there are no universally recognized criteria for preoperative diagnosis of MVI in clinical practice. Consequently, extensive research efforts have been directed towards preoperative imaging prediction of MVI to address this problem and the relative research progresses were reviewed in this article to summarize its current limitations and future research prospects.

Human papillomavirus-associated head and neck squamous cell carcinoma cells lose viability during triggered myocyte lineage differentiation

Head and neck squamous cell carcinoma (HNSCC) is a highly malignant disease, and death rates have remained at approximately 50% for decades. New tumor-targeting strategies are desperately needed, and a previous report indicated the triggered differentiation of HPV-negative HNSCC cells to confer therapeutic benefits. Using patient-derived tumor cells, we created a similar HNSCC differentiation model of HPV+ tumor cells from two patients. We observed a loss of malignant characteristics in differentiating cell culture conditions, including irregularly enlarged cell morphology, cell cycle arrest with downregulation of Ki67, and reduced cell viability. RNA-Seq showed myocyte-like differentiation with upregulation of markers of myofibril assembly. Immunofluorescence staining of differentiated and undifferentiated primary HPV+ HNSCC cells confirmed an upregulation of these markers and the formation of parallel actin fibers reminiscent of myoblast-lineage cells. Moreover, immunofluorescence of HPV+ tumor tissue revealed areas of cells co-expressing the identified markers of myofibril assembly, HPV surrogate marker p16, and stress-associated basal keratinocyte marker KRT17, indicating that the observed myocyte-like in vitro differentiation occurs in human tissue. We are the first to report that carcinoma cells can undergo a triggered myocyte-like differentiation, and our study suggests that the targeted differentiation of HPV+ HNSCCs might be therapeutically valuable.

The effect of different parameters of low-level laser used in the treatment of oral mucositis, on the viability and apoptosis of oral squamous cell carcinoma cells: Invitro study.

Oral mucositis is a complication of chemo/radiotherapy. To assess the impact of various power levels of diode-laser on the survival and expression of apoptosis-related genes in oral cancer cells, it is crucial to consider the potential existence of malignant cells within the treatment region and the reliance of laser effectiveness on its specific characteristics. Cal-27 cells were cultivated and exposed to a 660 nm-diode-laser at power levels of 20, 40, and 80 mW, alongside non-irradiated control cells. Viability and expression of Bax and Bcl-2 mRNA were assessed with Methyl Thiazolyl Tetrazolium (MTT) and Real-time Polymerase Chain Reaction (RT-PCR), respectively. The results were analyzed using one-way ANOVA and Tukey post-hoc test (p < 0.05). A significant reduction in viability was found only in the 20 mW group compared to controls (p = 0.001). Cell survival was significantly lower in cells receiving 20 mW laser than those treated with 40 and 80 mW (p < 0.05). None of the laser groups showed significant changes in BcL-2, but Bax was significantly lower in cells receiving 40 and 80 mW (p < 0.05), compared to controls. Laser irradiation at 660 nm (2 J/cm2, 30 s) significantly reduced the viability of oral cancer cells when using 20 mW power. These specifications align with the recommendation that the lowest possible laser dose should be applied for treating cancer patients. The exact mechanism of cell death following laser therapy with these specifications requires further investigation.

Risk of malignancy in effusions according to the International System for Serous Fluid Cytopathology: a review.

The International Serous Fluid Cytopathology Reporting System (TIS) was developed to standardize communication among health professionals reporting analyses of serous fluid samples. The categories include Non-Diagnosis (ND), Negative for Malignancy (NFM), Atypia of Undetermined Significance (AUS), Suspected Malignancy (SFM), and Malignant (MAL). Each category was characterized by a risk of malignancy (ROM). We performed a literature review to analyze studies related to TIS using several sources, including PubMed, followed by a search of relevant cytopathology journal websites (American Cancer Society, Diagnostic Cytopathology, Journal of the American Society of Cytopathology, and Acta Cytologica and Cytopathology). The search included articles published between January 2020 and December 2023, using the terms "international AND serous fluid system." We identified 257 articles, of which 20 addressed the inclusion and exclusion criteria. The overall ROMs for each category were 23.55% for ND, 16.46% for NFM, 50.78% for AUS, 91.34% for SFM, and 98.21% for MAL. Considering the TIS-recommended ROM rates, the ND category was between the suggested intervals, while the SFM category rate was larger than expected. The other categories (NFM, AUS, and MAL) were below expected values. SFM and MAL had a stronger association with malignant results. New studies are needed to determine each category's ROM rate from TIS accurately.