Malignant Research Articles

Four centrosome-related genes to predict the prognosis and drug sensitivity of patients with colon cancer

BACKGROUND As the primary microtubule organizing center in animal cells, centrosome abnormalities are involved in human colon cancer. AIM To explore the role of centrosome-related genes (CRGs) in colon cancer. METHODS CRGs were collected from public databases. Consensus clustering analysis was performed to separate the Cancer Genome Atlas cohort. Univariate Cox and least absolute shrinkage selection operator regression analyses were performed to identify candidate prognostic CRGs and construct a centrosome-related signature (CRS) to score colon cancer patients. A nomogram was developed to evaluate the CRS risk in colon cancer patients. An integrated bioinformatics analysis was conducted to explore the correlation between the CRS and tumor immune microenvironment and response to immunotherapy, chemotherapy, and targeted therapy. Single-cell transcriptome analysis was conducted to examine the immune cell landscape of core prognostic genes. RESULTS A total of 726 CRGs were collected from public databases. A CRS was constructed, which consisted of the following four genes: TSC1 , AXIN2 , COPS7A , and MTUS1 . Colon cancer patients with a high-risk signature had poor survival. Patients with a high-risk signature exhibited decreased levels of plasma cells and activated memory CD4+ T cells. Regarding treatment response, patients with a high-risk signature were resistant to immunotherapy, chemotherapy, and targeted therapy. COPS7A expression was relatively high in endothelial cells and fibroblasts. MTUS1 expression was high in endothelial cells, fibroblasts, and malignant cells. CONCLUSION We constructed a centrosome-related prognostic signature that can accurately predict the prognosis of colon cancer patients, contributing to the development of individualized treatment for colon cancer.

Undifferentiated high-grade pleomorphic sarcoma of the common bile duct: A case report and review of literature

BACKGROUND Undifferentiated pleomorphic sarcoma (UPS) is a rare malignant mesenchymal tumor with a poor prognosis. It mainly occurs in the extremities, trunk, head and neck, and retroperitoneum regions. Owing to the lack of specific clinical manifestations and imaging features, UPS diagnosis mainly depends on pathological and immunohistochemical examinations for exclusive diagnosis. Here we report an extremely rare case of high-grade UPS in the common bile duct (CBD). There are limited available data on such cases. CASE SUMMARY A 70-year-old woman was admitted to our department with yellow eyes and urine accompanied by upper abdominal distending pain for 2 wk. Her laboratory data suggested significantly elevated hepatorenal function levels. The imaging data revealed calculous cholecystitis, intrahepatic and extrahepatic bile duct dilation with extrahepatic bile duct calculi, and a space-occupying lesion at the distal CBD. After endoscopic biliary stenting and symptomatic support therapy, CBD exploration and biopsy were performed. The frozen section indicated malignant spindle cell tumor of the CBD mass, and further radical pancreaticoduodenectomy was performed. Finally, the neoplasm was diagnosed as a high-grade UPS combined with the light-microscopic morphology and immunohistochemical results. CONCLUSION This extremely rare case highlighted the need for increasing physicians' vigilance, reducing the odds of misdiagnosis, and providing appropriate treatment strategies.

Development and interpretation of a pathomics-driven ensemble model for predicting the response to immunotherapy in gastric cancer

BackgroundOnly a subset of patients with gastric cancer experience long-term benefits from immune checkpoint inhibitors (ICIs). Currently, there is a deficiency in precise predictive biomarkers for ICI efficacy. The aim...

METTL8 links mt-tRNA m3C modification to the HIF1α/RTK/Akt axis to sustain GBM stemness and tumorigenicity

Epitranscriptomic RNA modifications are crucial for the maintenance of glioma stem cells (GSCs), the most malignant cells in glioblastoma (GBM). 3-methylcytosine (m3C) is a new epitranscriptomic mark on RNAs and METTL8 represents an m3C writer that is dysregulated in cancer. Although METTL8 has an established function in mitochondrial tRNA (mt-tRNA) m3C modification, alternative splicing of METTL8 can also generate isoforms that localize to the nucleolus where they may regulate R-loop formation. The molecular basis for METTL8 dysregulation in GBM, and which METTL8 isoform(s) may influence GBM cell fate and malignancy remain elusive. Here, we investigated the role of METTL8 in regulating GBM stemness and tumorigenicity. In GSC, METTL8 is exclusively localized to the mitochondrial matrix where it installs m3C on mt-tRNAThr/Ser(UCN) for mitochondrial translation and respiration. High expression of METTL8 in GBM is attributed to histone variant H2AZ-mediated chromatin accessibility of HIF1α and portends inferior glioma patient outcome. METTL8 depletion impairs the ability of GSC to self-renew and differentiate, thus retarding tumor growth in an intracranial GBM xenograft model. Interestingly, METTL8 depletion decreases protein levels of HIF1α, which serves as a transcription factor for several receptor tyrosine kinase (RTK) genes, in GSC. Accordingly, METTL8 loss inactivates the RTK/Akt axis leading to heightened sensitivity to Akt inhibitor treatment. These mechanistic findings, along with the intimate link between METTL8 levels and the HIF1α/RTK/Akt axis in glioma patients, guided us to propose a HIF1α/Akt inhibitor combination which potently compromises GSC proliferation/self-renewal in vitro. Thus, METTL8 represents a new GBM dependency that is therapeutically targetable.

Validating reference-based algorithms to determine cell-type heterogeneity in ovarian cancer DNA methylation studies

Information about cell composition in tissue samples is crucial for biomarker discovery and prognosis. Specifically, cancer tissue samples present challenges in deconvolution studies due to mutations and genetic rearrangements. Here, we optimized a robust, DNA methylation-based protocol, to be used for deconvolution of ovarian cancer samples. We compared several state-of-the-art methods (HEpiDISH, MethylCIBERSORT and ARIC) and validated the proposed protocol in an in-silico mixture and in an external dataset containing samples from ovarian cancer patients and controls. The deconvolution protocol we eventually implemented is based on MethylCIBERSORT. Comparing deconvolution methods, we paid close attention to the role of a reference panel. We postulate that a possibly high number of samples (in our case: 247) should be used when building a reference panel to ensure robustness and to compensate for biological and technical variation between samples. Subsequently, we tested the performance of the validated protocol in our own study cohort, consisting of 72 patients with malignant and benign ovarian disease as well as in five external cohorts. In conclusion, we refined and validated a reference-based algorithm to determine cell type composition of ovarian cancer tissue samples to be used in cancer biology studies in larger cohorts.

Brevilin A Inhibits Prostate Cancer Progression by Decreasing PAX5-Activated SOX4.

Brevilin A possesses inhibitory effects on the development of prostate cancer (PCa); however, the underlying mechanism remains unclear. The present work aims to analyze how Brevilin A regulates PCa cell malignancy. RNA expression of paired box 5 (PAX5) and SRY-box transcription factor 4 (SOX4) was analyzed by quantitative real-time polymerase chain reaction. Protein expression of PAX5, SOX4, and nuclear proliferation marker (Ki67) was detected by western blotting or immunohistochemistry assay. The viability, proliferation, apoptosis, and migratory and invasive abilities of PCa cells were investigated by cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU), flow cytometry, and transwell assays, respectively. The association between PAX5 and SOX4 was identified by dual-luciferase reporter assay and chromatin immunoprecipitation assay. Xenograft mouse model assay was used to reveal the effect of Brevilin A on tumor tumorigenesis in vivo. PAX5 and SOX4 expression were upregulated in PCa tissues and cells relative to normal prostate tissues and human prostate epithelial cells. Brevilin A treatment inhibited PAX5 protein expression in PCa cells. Additionally, Brevilin A inhibited proliferation, migration and invasion and induced apoptosis of PCa cells, whereas these effects were attenuated after PAX5 overexpression. SOX4 was transcriptionally activated by PAX5, and its introduction partially relieved the inhibitory effects of PAX5 knockdown on PCa cell malignancy. Moreover, Brevilin A delayed tumor formation in vivo. Brevilin A inhibited PCa progression by regulating SOX4 expression in a PAX5-dependent manner, providing a promising anti-tumor drug for PCa.

Malignant Abrikossoff’s Tumour of the Tonsil - A Case Report of a Rare Entity

Abstract Rationale: This study aimed to report an uncommon site of origin of a rare head-and-neck cancer, namely malignant granular cell tumour. Patient Concerns: An 89-year-old female patient complained of persistent pharyngodynia and odynophagia for two months. Diagnosis: Upon clinical examination, the right palatine tonsil was larger and palpably firmer than the contralateral. An incisional biopsy of the lesion was performed under local anaesthesia revealing malignant granular cell tumour. A contrast-enhanced computed tomography (CECT) scan of the head and neck and an 18F-fluoro-2-deoxy-D-glucose positron emission tomography (PET) scan confirmed the presence of a pathologic appearance of the right palatine tonsil without nodal or distant metastasis. Treatment: Following a multidisciplinary consultation and the patient’s informed permission, a right tonsillectomy extended to the constrictor muscle fibres of the upper pharynx was performed. Outcomes: The tumour was staged as pT2 R0 cN0 M0, according to the AJCC 8th edition for soft-tissue tumours of the head and neck. Due to the early stage and the radicality of surgery, no further adjuvant treatments were provided. The patient is currently followed up with no evidence of disease one year post-operatively. Take-away Lessons: Granular cell tumours are rare mesenchymal tumours, firstly described by the pathologist Abrikossoff in 1926. This type of tumour constitutes approximately 0.5% of all soft-tissue tumours, and can affect any part of the body, with the head and neck being the most frequently involved site. The tonsil is an extremely rare localisation of this cancer. The differential diagnosis of unilateral tonsillar enlargement should also include this histological entity.

Deep PIM kinase substrate profiling reveals new rational co-therapeutic strategies for acute myeloid leukemia.

Provirus integration site for Moloney murine leukemia virus (PIM) family serine/threonine kinases perform pro-tumorigenic functions in hematologic malignancies and solid tumors by phosphorylating substrates involved in tumor metabolism, cell survival, metastasis, inflammation, and immune cell invasion. However, a comprehensive understanding of PIM kinase functions is currently lacking. Multiple small molecule PIM kinase inhibitors are currently being evaluated as co-therapeutics in cancer patients. To further illuminate PIM kinase functions in cancer, we deeply profiled PIM1 substrates using the reverse in-gel kinase assay to identify downstream cellular processes targetable with small molecules. Pathway analyses of putative PIM substrates nominated RNA splicing and rRNA processing as PIM-regulated cellular processes. PIM inhibition elicited reproducible splicing changes in PIM-inhibitor-responsive acute myeloid leukemia (AML) cell lines. PIM inhibitors synergized with splicing modulators targeting splicing factor 3b subunit 1 (SF3B1) and serine-arginine protein kinase 1 (SRPK1) to kill AML cells. PIM inhibition also altered rRNA processing, and PIM inhibitors synergized with an RNA polymerase I inhibitor to kill AML cells and block AML tumor growth. These data demonstrate that deep kinase substrate knowledge can illuminate unappreciated kinase functions, nominating synergistic co-therapeutic strategies. This approach may expand the co-therapeutic armamentarium to overcome kinase-inhibitor resistant disease that limits durable responses in malignant disease.

Diagnosis of Serous Effusion with Intelligent Imaging Flow Cytometry

AbstractA serous effusion is a buildup of extra fluid in the serous cavities including pleural, peritoneal, and pericardial cavities. It is important to distinguish benign reactive effusions from effusions caused by malignant proliferation in cytopathology since different diagnoses can lead to completely different disease staging and therapeutic choices. The conventional cytopathology procedure has the disadvantages of low throughput and low objectivity. To enhance the efficiency and accuracy of malignant serous effusion diagnosis, in this paper, an imaging flow cytometry, called optofluidic time‐stretch microscopy is first employed, to image the cells in the serous effusion at an event rate of 100 000 events per second and with a spatial resolution better than 1 µm. The acquired cellular images are then analyzed using a convolutional neural network, by which the malignant cells are accurately detected. The performance of the method is validated with 18 clinical samples, including 14 malignant and 4 benign ones. The results show that the method can detect malignant cells at an accuracy of 90.53%. The high throughput, high accuracy, and high convenience of the method make it a potential solution for malignant serous effusion diagnosis in various scenarios.

Comprehensive analysis of competing endogenous RNA networks involved in the regulation of glycolysis in clear cell renal cell carcinoma

Abstract Objectives This study aims to elucidate the role of competing endogenous RNAs (ceRNAs), which are pivotal in the post-transcriptional regulation of cancer cells, in the glycolysis of clear cell renal cell carcinoma (ccRCC). Methods RNA-seq data from ccRCC samples and public datasets were subjected to differential expression analysis to identify the upregulated circular RNAs (circRNAs), long noncoding RNAs (lncRNAs), and mRNAs for constructing a ceRNA network. This network focused on the upregulated mRNAs linked to glycolysis and gluconeogenesis, which were verified at the proteome level using the CPTAC database. The ENCORI database was used to predict the lncRNA/circRNA-miRNA and miRNA-mRNA interactions, which formed a network visualized using Cytoscape. This study further examined the association of selected lncRNAs/circRNAs with biological processes and patient survival and explored lncRNA and mRNA expressions at the single-cell level. Results Three circRNAs and eight lncRNAs were identified to be regulators of four glycolysis pathway genes (HK2, LDHA, PFKP, and ALDOC) via 54 miRNAs. Notably, their expressions were aberrant at the transcriptome and proteome levels. These RNA elements were correlated with malignant and immune pathways, and several lncRNAs showed prognostic significance for ccRCC. Furthermore, single-cell RNA sequencing indicated the abnormal enrichment of these lncRNAs and mRNAs in malignant cells. Conclusions This study identified a ceRNA network that plays a critical role in the glycolysis of ccRCC. These findings highlight the importance of ceRNAs in cancer malignancy and their potential impact on patient prognosis.

Resolvin D1 Inhibits IL-6-Induced Epithelial-Mesenchymal Transition of Colorectal Cancer Cells by Targeting IL-6/STAT3 Signaling.

Colorectal cancer (CRC) has emerged as a prevalent malignancy worldwide, exhibiting the high morbidity and mortality rates. Resolvin D1 (RvD1) can exert anti-inflammation and anti-cancer effects on various diseases. This study is aimed to explore the role of RvD1 in CRC cells. HCT15 and SW480 cells were stimulated with IL-6 in our study. A series of assays such as CCK-8, colony formation, wound healing, Transwell, Western blotting, and immunofluorescence staining were designed and conducted to figure out the role of RvD1 in CRC cells. RvD1 suppressed IL-6-induced SW480 and HCT15 cell proliferation. In addition, RvD1 inhibited IL-6-induced SW480 and HCT15 cell migration, invasion, and EMT process. In mechanism, RvD1 inhibited the activation of IL-6/STAT3 signaling in SW480 and HCT15 cells. Angoline strengthened the inhibitive effect of RvD1 on cell malignancy. RvD1 inhibited cell growth, migration, invasion and EMT process by inactivating IL-6/STAT3 signaling in CRC.

Sarcomatoid and Rhabdoid Renal Cell Carcinoma: Clinical, Pathologic, and Molecular Genetic Features.

Renal cell carcinoma (RCC) with sarcomatoid and rhabdoid morphologies has an aggressive biological behavior and a typically poor prognosis. The current 2022 WHO classification of renal tumors does not include them as distinct histologic entities but rather as transformational changes that may arise in a background of various distinct histologic types of RCC. The sarcomatoid component shows malignant spindle cells that may grow as intersecting fascicles, which is reminiscent of pleomorphic undifferentiated sarcoma. The rhabdoid cells are epithelioid cells with eccentrically located vesicular nuclei with prominent nucleoli and large intracytoplasmic eosinophilic inclusions. Studies have shown that RCCs with sarcomatoid and rhabdoid differentiation have distinctive molecular features. Sarcomatoid RCC harbors shared genomic alterations in carcinomatous and rhabdoid components, but also enrichment of specific genomic alterations in the sarcomatoid element, suggesting molecular pathways for development of sarcomatoid growth from a common clonal ancestor. Rhabdoid differentiation also arises through clonal evolution although less is known of specific genomic alterations in rhabdoid cells. Historically, treatment has lacked efficacy, although recently immunotherapy with PD-1/PD-L1/CTLA-4 inhibitors has produced significant clinical responses. Reporting of sarcomatoid and rhabdoid features in renal cell carcinoma is required by the College of American Pathologists and the International Collaboration on Cancer Reporting. This manuscript reviews the clinical, pathologic, and molecular features of sarcomatoid RCC and rhabdoid RCC with emphasis on the morphologic features of these tumors, significance of diagnostic recognition, the molecular mechanisms of tumorigenesis and differentiation along sarcomatoid and rhabdoid lines, and advances in treatment, particularly immunotherapy.

An Intelligent Telediagnosis of Acute Lymphoblastic Leukemia using Histopathological Deep Learning

Leukemia, a global health challenge characterized by malignant blood cell proliferation, demands innovative diagnostic techniques due to its increasing incidence. Among leukemia types, Acute Lymphoblastic Leukemia (ALL) emerges as a particularly aggressive form affecting diverse age groups. This study proposes an advanced mechanized system utilizing Deep Neural Networks for detecting ALL blast cells in microscopic blood smear images. Achieving a remarkable accuracy of 97% using MobileNetV2, our system demonstrates high sensitivity and specificity in identifying multiple ALL sub-types. Furthermore, we introduce cutting-edge telediagnosis software facilitating real-time support for clinicians in promptly and accurately diagnosing various ALL subtypes from microscopic blood smear images. This research aims to enhance leukemia diagnosis efficiency, which is crucial for the timely intervention and managing this life-threatening condition.

Case report: Abdominal mesothelioma in Atelerix albiventris

Hedgehogs, as exotic species, are more susceptible to various neoplastic conditions affecting diverse bodily systems, particularly the tegumentary, hemolymphatic, and digestive systems. Among these conditions, epithelial tumors are the most prevalent, followed by round cell tumors and mesenchymal tumors. A striking characteristic is the malignant nature of over 8% of these tumors, leading to a generally unfavorable prognosis. This study aims to present a unique case involving a 2.5 year-old male African pygmy hedgehog in Concepción, Biobío District, Chile, diagnosed with a mesenchymal neoplasia originating from mesothelial cells. The hedgehog presented to the veterinary clinic with acute abdominal pain, prompting ultrasound imaging, and comprehensive cytological, histopathological, and immunohistochemical analyses. During abdominal ultrasound, a mass was observed, and its cytological examination revealed the presence of malignant cells. The histopathological examination unveiled a diffuse mesothelial cell tissue interwoven with abundant fibrous tissue and small cysts containing serous fluid, all enveloped by flattened or cuboidal cells of mesothelial origin. Immunohistochemistry further confirmed the diagnosis, demonstrating positive immunostaining for calretinin and mesothelin markers, corroborating the diagnosis of fibrous malignant peritoneal mesothelioma. This case highlights the complexity of neoplastic conditions in hedgehogs and emphasizes the importance of multimodal diagnostic approaches for accurate identification and understanding of these rare diseases.

In situ ascending aortic thrombus in a patient with metastatic lung adenocarcinoma and no aortic atherosclerosis or cisplatin exposure: a case report

BackgroundAn ascending aortic thrombus is exceedingly rare. Two instances have been reported in the setting of lung cancer, but only after cisplatin use, which is associated with hypercoagulability. We present the first case of a patient with lung cancer who developed an ascending aortic thrombus without structural risk factors or chemotherapy use.CaseA 60-year-old white female with significant smoking history presented with several weeks of malaise. A chest computed tomography scan revealed a 2.2-cm right upper lobe mass. As an outpatient, right hilar lymph node immunohistochemistry (IHC) samples via endobronchial ultrasound confirmed thyroid transcription factor-1 adenocarcinoma. After the procedure, the patient endorsed dyspnea and was advised to go to the emergency department. A chest computed tomography angiography identified a new 2.4 × 1.1 × 1.1 cm thrombus within the proximal aortic arch. No pulmonary emboli or intrapulmonary shunts were identified. A hypercoagulable workup was negative. Transthoracic echocardiogram was without left ventricular thrombus, akinesis or hypokinesis, left atrial dilation, or intracardiac shunts. A lower extremity ultrasound was negative for deep vein thrombosis. Given the procedural risk, thrombectomy was deferred. The patient was transitioned to enoxaparin, and a repeat computed tomography for resolution is in process.ConclusionTo our knowledge, this is the only case detailing an in situ ascending aortic thrombus in the setting of lung cancer, without structural risk factors, chemotherapy use, or other hypercoagulable comorbidities. Optimal management for an aortic thrombus and malignant disease is less clear. Clinicians should be vigilant for unusual arterial thromboses in patients with high metastatic burden.

TIF1β activates leukemic transcriptional program in HSCs and promotes BCR::ABL1-induced myeloid leukemia.

TIF1β/KAP1/TRIM28, a chromatin modulator, both represses and activates the transcription of genes in normal and malignant cells. Analyses of datasets on leukemia patients revealed that the expression level of TIF1β was increased in patients with chronic myeloid leukemia at the blast crisis and acute myeloid leukemia. We generated a BCR::ABL1 conditional knock-in (KI) mouse model, which developed aggressive myeloid leukemia, and demonstrated that the deletion of the Tif1β gene inhibited the progression of myeloid leukemia and showed longer survival than that in BCR::ABL1 KI mice, suggesting that Tif1β drove the progression of BCR::ABL1-induced leukemia. In addition, the deletion of Tif1β sensitized BCR::ABL1 KI leukemic cells to dasatinib. The deletion of Tif1β decreased the expression levels of TIF1β-target genes and chromatin accessibility peaks enriched with the Fosl1-binding motif in BCR::ABL1 KI stem cells. TIF1β directly bound to the promoters of proliferation genes, such as FOSL1, in human BCR::ABL1 cells, in which TIF1β and FOSL1 bound to adjacent regions of chromatin. Since the expression of Fosl1 was critical for the enhanced growth of BCR::ABL1 KI cells, Tif1β and Fosl1 interacted to activate the leukemic transcriptional program in and cellular function of BCR::ABL1 KI stem cells and drove the progression of myeloid leukemia.

Immediate dental rehabilitation in fibula free flaps for malignancy: Is it feasible?

Fibula free flap reconstruction has revolutionized maxillofacial reconstruction. While immediate dental rehabilitation with dental implants and teeth has shown benefits, it remains uncommon, especially for patients with malignancy. A retrospective cohort study at a single institution explored immediate dental rehabilitation in fibula flaps for patients with malignant disease. Thirteen patients with malignancies that underwent immediate fibula free flap reconstruction with dental implants and dental prosthesis were included with a minimum of 3-month follow-up. Forty eight implants replaced 90 teeth in 13 patients. All implants were integrated at 3 months, with an overall success rate of 87.5%. Two patients experienced delayed (>3 months postoperatively) implant loss due to osteoradionecrosis and infection. Peri-mucositis occurred in three patients which resolved with treatment. Skin paddles were used in 11 patients and radiation therapy was not delayed for any patient. With proper patient selection, diagnosis of malignancy and the need for osteocutaneous flap reconstruction does not exclude the ability to place immediate implants and deliver an immediate dental prosthesis in head and neck reconstruction.

Serving Those Who Served: Enhancing Colorectal Surgery Care for Veterans

AbstractThe Department of Veterans Affairs (VA) is the largest provider of integrated health care services in the United States and its mission is to honor veterans by providing timely, effective, and high-quality health care that improves individuals' health and functionality. The VA provides comprehensive primary and specialty care, including colorectal surgery services, to eligible veterans who suffer from a disproportionately high burden of medical comorbidities and often belong to vulnerable populations, including individuals of low socioeconomic status, those who identify as lesbian, gay, bisexual, transgender, and questioning, racial minorities, and those suffering from severe mental health illness. There are many challenges to caring for a population of veterans with benign and malignant colorectal disease due to both patient and system level factors. Despite these challenges, the VA has demonstrated a commitment to ensuring culturally competent, equitable, and inclusive care and to conducting research that establishes evidence-based best practices in the management of colorectal diseases. These efforts have led to outcomes for patients undergoing care for colorectal diseases within the VA that are par with or better than civilian outcomes. The VA is uniquely positioned on a system level to provide nationwide efforts that improve care delivery and serve those who served.

Effectiveness and safety of SR-ENS-600endoscopic surgical system in benign and malignant gynecological diseases: a prospective, multicenter, clinical trial with 63 cases

Single-port laparoscopy has gained more attention, but inherent technical challenges hinder its wider use. To overcome the disadvantage of traditional single-port surgery, robotic laparoendoscopic single-site surgery system was designed and clinically utilized. This multi-center single-arm trial was aimed to present the clinical outcomes of the SHURUI robotic endoscopic single-site surgery system. 63 women with ovary cysts, myoma, cervical epithelial neoplasm, or endometrial carcinoma were recruited at 6 academic medical centers in different districts of China. The trial was registered on September 5, 2023, with the register number: ChiCTR2300075431, retrospectively registered. Patients underwent robotic LESS surgery with the SHURUI endoscopic surgical system from January 17 to May 26, 2023. Demographic information, perioperative parameters, complications, scar healing, and operator satisfaction scores were recorded. Patients were followed up for 30 ± 4 days. Average operative time and estimated blood loss were 157.03 ± 75.24 min and 63.86 ± 98.33 ml, respectively, for all surgeries. Average anal exhaust time and hospitalization stay were 30.99 ± 14.25 h and 3.63 ± 1.59 days, respectively. Patients’ postoperative rehabilitation assessment showed satisfactory results on the day of discharge and 30 ± 4 days after surgery. The surgery achieved good cosmetic benefits and was surgeon friendly. There were no conversions to alternative surgical modalities, complications, or readmissions. The SHURUI endoscopic surgical system showed both the technical feasibility and safety of this surgical modality for gynecologic patients. Further randomized studies comparing this modality with traditional LESS surgery are suggested.

Activated interferon response from DNA damage in multiple myeloma cells contributes to the chemotherapeutic effects of anthracyclines

IntroductionMultiple myeloma (MM) is a malignant plasma cell disease caused by abnormal proliferation of clonal plasma cells in bone marrow. Upfront identification of tumor subgroups with specific biological markers has the potential to improve biologically-driven therapy. Previously, we established a molecular classification by stratifying multiple myeloma into two subtypes with a different prognosis based on a gene module co-expressed with MCL-1 (MCL1-M).MethodsGene Ontology (GO) analysis with differentially expressed genes was performed to identify signal pathway. Drug sensitivity was analyzed using the OncoPredict algorithm. Drug sensitivity of different myeloma cell lines was detected by CCK8 and flow cytometry. RNA-seq was performed on drug-sensitive cell lines before and after adriamycin treatment. RT-qPCR was used to further verify the sequencing results. The expression of γ-H2AX and dsDNA in sensitive and resistant cell lines was detected by immunofluorescence method.ResultsIn our study, we demonstrated that MCL1-M low MM were more sensitive to anthracyclines. We treated different myeloma cell lines with doxorubicin in vitro and discovered the association of drug sensitivity with IFN signaling. Herein, we demonstrate that the doxorubicin-sensitive myeloma cell line showed significant DNA damage and up-regulated expression of genes related to the IFN response, which was not observed in drug-insensitive cell lines.DiscussionOur results suggest that the active IFN signaling pathway may serve as a marker for predicting chemotherapy sensitivity in patients with myeloma. With our MCL1-M molecular classification system, we can screen patients with a potentially good response to the interferon signaling pathway and provide individualized treatment for MM. We propose IFN-a as adjuvant therapy for patients with myeloma sensitive to anthracyclines to further improve the therapeutic effect and prolong the survival of patients.