Metastatic Cell Research Articles

Numerical investigation on flow-induced wall shear stress variation of metastatic cancer cells in lymphatics with elastic valves.

Hematogenous metastasis occurs when cancer cells detach from the extracellular matrix in the primary tumor into the bloodstream or lymphatic system. Elucidating the response of metastatic tumor cells in suspension to the flow conditions in lymphatics with valves from a mechanical/fluidic perspective is necessary. A physiologically relevant computational model of a lymphatic vessel with valves was constructed using fully coupled fluid-cell-vessel interactions to investigate the effects of lymphatic vessel contractility, valve properties, and cell size and stiffness on the variations in magnitude and gradient of the flow-induced wall shear stress (WSS) experienced by suspended tumor cells. Results indicated that the maximum WSSmax increased with the increments in cell diameter, vessel contraction amplitude, and valve stiffness. The decrease in vessel contraction period and valve aspect ratio also increased the maximum WSSmax. The influence of the properties of the valve on the WSS was more significant among the factors mentioned above. The maximum WSSmax acting on the cancer cell when the cell reversed the direction of its motion in the valve region increased by 0.5-1.4 times that before the cell entered the valve region. The maximum change in WSS was in the range of 0.004-0.028 Pa/µm depending on the factors studied. They slightly exceeded the values associated with breast cancer cell apoptosis. The results of this study provide biofluid mechanics-based support for mechanobiological research on the metastasis of metastatic cancer cells in suspension within the lymphatics.

Netrin signaling mediates survival of dormant epithelial ovarian cancer cells.

Dormancy in cancer is a clinical state in which residual disease remains undetectable for a prolonged duration. At a cellular level, rare cancer cells cease proliferation and survive chemotherapy and disseminate disease. We created a suspension culture model of high-grade serous ovarian cancer (HGSOC) dormancy and devised a novel CRISPR screening approach to identify survival genes in this context. In combination with RNA-seq, we discovered the Netrin signaling pathway as critical to dormant HGSOC cell survival. We demonstrate that Netrin-1, -3, and its receptors are essential for low level ERK activation to promote survival, and that Netrin activation of ERK is unable to induce proliferation. Deletion of all UNC5 family receptors blocks Netrin signaling in HGSOC cells and compromises viability during the dormancy step of dissemination in xenograft assays. Furthermore, we demonstrate that Netrin-1 and -3 overexpression in HGSOC correlates with poor outcome. Specifically, our experiments reveal that Netrin overexpression elevates cell survival in dormant culture conditions and contributes to greater spread of disease in a xenograft model of abdominal dissemination. This study highlights Netrin signaling as a key mediator HGSOC cancer cell dormancy and metastasis.

GDNF-induced phosphorylation of MUC21 promotes pancreatic cancer perineural invasion and metastasis by activating RAC2 GTPase.

Perineural invasion (PNI) is an adverse prognostic feature of pancreatic ductal adenocarcinoma (PDAC). However, the understanding of the interactions between tumors and neural signaling within the tumor microenvironment is limited. In the present study, we found that MUC21 servers as an independent risk factor for poor prognosis in PDAC. Furthermore, we demonstrated that MUC21 promoted the metastasis and PNI of PDAC cells by activating JNK and inducing epithelial-mesenchymal transition (EMT). Mechanistically, glial cell-derived neurotrophic factor, secreted by Schwann cells, phosphorylates the intracellular domain S543 of MUC21 via CDK1 in PDAC cells, facilitating the interaction between MUC21 and RAC2. This interaction leads to membrane anchoring and activation of RAC2, which in turn activates the JNK/ZEB1/EMT axis, ultimately enhancing the metastasis and PNI of PDAC cells. Our results present a novel mechanism of PNI, suggesting that MUC21 is a potential prognostic marker and therapeutic target for PDAC.

Discordance of retroperitoneal and thoracic histologic findings in patients with metastatic germ cell tumors at postchemotherapy residual tumor resection

Introduction and objectivesPostchemotherapy residual tumor resection (PC-RTR) is an important part of the multimodal treatment for patients with metastatic germ cell tumors. Simultaneous retroperitoneal and thoracic metastases often require consecutive surgical procedures. This study analyzes the histologic findings after abdominal and thoracic surgery in order to tailor the sequence and intensity of surgery.Patients and methodsFrom a total of 671 PC-RTRs from 2008 to 2021 we analyzed 50 patients with stage III non-seminomatous germ cell tumor (NSGCT) who had undergone both retroperitoneal and thoracic postchemotherapy residual tumor resection after first-line and salvage chemotherapy.ResultsAll patients included had stage III NSGCT. 39 and 11 patients received first-line and salvage chemotherapy, respectively. 45 (90%) patients received retroperitoneal resection first, followed by thoracic surgery. Three patients (6%) underwent thoracic surgery before retroperitoneal surgery and two patients (4%) underwent simultaneous surgery. Overall, the histology of retroperitoneal and thoracic specimens was discordant in 23% of cases. After first-line chemotherapy, of fourteen patients with necrosis in retroperitoneal histology, four patients had vital carcinoma in lung histology. In patients with teratoma in the retroperitoneum, the thoracic findings were concordant in most cases (78%). When teratomatous elements were also present in the orchiectomy specimen, concordance was 100%. After salvage chemotherapy, the discordance rate was 55%.ConclusionThe data presented in this study underline that retroperitoneal residual masses with necrosis cannot reliably predict histologic findings of thoracic specimens. Patients with teratoma in the retroperitoneum have a high likelihood of teratoma in the thoracic specimen.

Cost-efficiency and budget-neutral expanded access modeling of pembrolizumab versus the novel PD-1 inhibitor toripalimab in locally advanced or metastatic nonsquamous non-small cell lung cancer

Aims To estimate in a panel of patients with locally advanced/metastatic nonsquamous non-small cell lung cancer (NSCLC) treated with a programmed death receptor-1 inhibitor in the US in 2024 (1) the cost-efficiency of toripalimab regimens compared to pembrolizumab regimens; and (2) the budget-neutral expanded access to additional toripalimab cycles and regimens from accrued savings. Methods Simulation modeling of toripalimab + pemetrexed + carboplatin in nonsquamous NSCLC to a similar pembrolizumab regimen in a panel of 49,647 patients; utilizing two cost inputs (wholesale acquisition cost (WAC) at market entry and an estimated ex ante toripalimab price point of 80% of pembrolizumab average sales price (ASP)) plus administration costs over one and two years of treatment with treatment rates from 1%-10%. Scenario analyses with treatment durations equivalent to toripalimab and pembrolizumab trials’ median PFS were also conducted. Results In the WAC-based models, toripalimab saves $2,223 per patient per cycle and $40,014 over 1 year of treatment ($77,805 over 2 years). Extrapolated to the 49,647-patient panel, estimated 1-year savings range from $19,865,840 (1% treatment rate) to $198,658,399 (10% rate). Reallocating these savings permits budget-neutral expanded access to an additional 1,753 (1% rate) to 17,533 (10% rate) toripalimab maintenance cycles or to an additional 97 (1% rate) to 972 (10%) full 1-year toripalimab regimens with all agents. Two-year savings range from $38,628,022 (1% rate) to $386,280,221 (10%). Reallocating these efficiencies provides expanded access ranging from 3,409 (1% rate) to 34,093 (10%) additional toripalimab cycles or to 97 to 973 full 2-year regimens. The ex ante ASP model showed similar results as did the scenario analyses but at a lower magnitude than the base case. Conclusion Toripalimab generates significant savings that enable budget-neutral funding for up to 17,533 [34,093] additional maintenance cycles over one year [two years] with toripalimab + pemetrexed in nonsquamous NSCLC, or 972 [973] full one-year [two-year] regimens.

Chondroitin sulfate proteoglycan 4 (CSPG4) increases invasion of recessive dystrophic epidermolysis bullosa-associated cutaneous squamous cell carcinoma by modifying TGFβ signaling.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic skin-blistering disorder often progressing to metastatic cutaneous squamous cell carcinoma (cSCC) at chronic wound sites. Chondroitin sulfate proteoglycan 4 (CSPG4) is a cell-surface proteoglycan that is an oncoantigen in multiple malignancies, where it modulates oncogenic signaling, drives epithelial-to-mesenchymal transition (EMT), and enables cell motility. To evaluate CSPG4 expression and function in RDEB-cSCC. RDEB-cSCC cell lines were used to assess CSPG4-dependent changes in invasive potential, TGFβ1-stimulated signal activation, and clinically relevant cytopathology metrics in an in vitro full-thickness tumor model. CSPG4 expression in RDEB-cSCC and non-RDEB cSCC tumors was analyzed via immunohistochemistry and single-cell RNA sequencing (scRNA-seq), respectively. Inhibiting CSPG4 expression reduced invasive potential in multiple RDEB-cSCC cell lines and altered membrane-proximal TGFβ signal activation through changes in SMAD3 phosphorylation. CSPG4 expression was uniformly localized to basal-layer keratinocytes in fibrotic RDEB skin and tumor cells at the tumor/stroma interface at the invasive front in RDEB-cSCC tumors in vivo. Analysis of published scRNA-seq data revealed that CSPG4 expression was correlated with an enhanced EMT transcriptomic signature in cells at the tumor/stroma interface of non-RDEB cSCC tumors. Cytopathological metrics, like nucleus:cell area ratio, were influenced by CSPG4 expression in in vitro tumor models. We determined that CSPG4 expression in RDEB-cSCC cell lines enhanced invasive potential. Mechanistically, CSPG4 was found to enhance membrane-proximal TGFβ-stimulated signaling through SMAD3, which is a key mediator of EMT in RDEB-cSCC. The implication of these studies is that CSPG4 may represent a therapeutic target that can be leveraged for clinical management in patients with RDEB-cSCC.

Histone lactylation facilitates hepatocellular carcinoma progression by upregulating endothelial cell-specific molecule 1 expression.

Hepatocellular carcinoma (HCC) is a common malignant tumor. Histone lactylation, a novel epigenetic modification, plays a crucial role in various cancers. However, the functional role and underlying mechanism of histone lactylation in HCC progression have not yet been investigated. Histone lactylation levels in HCC tissues and cells were assessed using a densitometric kit and western blot analysis. The role of histone lactylation in cell malignant phenotypes was determined through functional assays in vitro, and a xenograft tumor model was established to verify the function of histone lactylation in vivo. ChIP assay was performed to explore the interaction between histone lactylation and endothelial cell-specific molecule 1 (ESM1). Additionally, gain-and-loss-of-function assays were conducted to investigate the regulatory role of ESM1 in HCC pathogenesis. Histone lactylation levels were increased in HCC tissues and cells, and H3K9 lactylation (H3K9la) and H3K56 lactylation (H3K56la) were identified as the histone modification sites. We observed that H3K9la and H3K56la caused abnormal histone lactylation and were associated with poor prognosis. Functionally, histone lactylation was found to promote HCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) process in vitro. However, histone lactylation inhibition with 2-deoxy-d-glucose (2-DG) reduced the malignant phenotypes of HCC cells. In vivo, 2-DG treatment reduced tumor growth and metastasis in the HCC mouse model. Mechanistically, it was revealed that histone lactylation activated ESM1 transcription in HCC cells. ESM1 was expressed at a high level in HCC and exerted a carcinogenic role. Histone lactylation facilitates cell malignant phenotypes, tumor growth, and metastasis by upregulating ESM1 expression in HCC, which reveals the downstream molecular mechanism of histone lactylation and might provide a novel therapeutic target for HCC therapy.

Innovating Cancer Treatment Through Cell Cycle, Telomerase, Angiogenesis, and Metastasis.

Cancer remains a formidable challenge in the field of medicine, necessitating innovative therapeutic strategies to combat its relentless progression. The cell cycle, a tightly regulated process governing cell growth and division, plays a pivotal role in cancer development. Dysregulation of the cell cycle allows cancer cells to proliferate uncontrollably. Therapeutic interventions designed to disrupt the cell cycle offer promise in restraining tumor growth and progression. Telomerase, an enzyme responsible for maintaining telomere length, is often overactive in cancer cells, conferring them with immortality. Targeting telomerase presents an opportunity to limit the replicative potential of cancer cells and hinder tumor growth. Angiogenesis, the formation of new blood vessels, is essential for tumor growth and metastasis. Strategies aimed at inhibiting angiogenesis seek to deprive tumors of their vital blood supply, thereby impeding their progression. Metastasis, the spread of cancer cells from the primary tumor to distant sites, is a major challenge in cancer therapy. Research efforts are focused on understanding the underlying mechanisms of metastasis and developing interventions to disrupt this deadly process. This review provides a glimpse into the multifaceted approach to cancer therapy, addressing critical aspects of cancer biology-cell cycle regulation, telomerase activity, angiogenesis, and metastasis. Through ongoing research and innovative strategies, the field of oncology continues to advance, offering new hope for improved treatment outcomes and enhanced quality of life for cancer patients.

Discovery, Synthesis, and Activity Evaluation of Novel Five-Membered Sulfur-Containing Heterocyclic Nucleosides as Potential Anticancer Agents In Vitro and In Vivo.

A series of novel five-membered sulfur-containing heterocyclic nucleoside derivatives were designed, synthesized, and evaluated for their anticancer activities in vitro and in vivo. The structure-activity relationship studies revealed that some of them showed obvious antitumor activities in several cancer cell lines. Among them, compound 22o exhibited remarkable antiproliferative activity against HeLa cells and was more potent than cisplatin (IC50 = 2.80 vs 7.99 μM). Furthermore, mechanism studies indicated that 22o inhibited cell metastasis, induced cell apoptosis, decreased mitochondrial membrane potential, and activated autophagy through the PI3K-Akt-mTOR signaling pathway. Moreover, drug affinity responsive target stability and the cellular thermal shift assay revealed that 22o targeted RPS6 and inhibited its phosphorylation. Importantly, 22o inhibited the growth of the HeLa xenograft mouse model with a low systemic toxicity. These results indicated that 22o may serve as potent anticancer agents that merit further attention in future anticancer drug discovery.

LAIR1 promotes hepatocellular carcinoma cell metastasis and induces M2-macrophage infiltration through activating AKT-IKKβ-p65 axis.

LAIR1, a receptor found on immune cells, is capable of binding to collagen and is involved in immune-related diseases. However, the precise contribution of LAIR1 expressed on hepatocellular carcinoma (HCC)cells to tumor microenvironment is still unclear. In our study, bioinformatics analysis and immunofluorescence were employed to study the correlation between LAIR1 levels and clinical indicators. Transwell and scratch tests were used to evaluate how LAIR1 affected the migration and invasion of HCC cells. The chemotactic capacity and alternative activation of macrophages were investigated using RT-qPCR,transwell, and immunofluorescence. To investigate the molecular mechanisms, transcriptome sequencing analysis, Western blot, nucleus/cytoplasm fractionation, ELISA, and cytokine microarray were employed. We revealed a significant correlation between the presence of LAIR1 and an unfavorable outcome in HCC. We indicated that LAIR1 promoted migration and invasion of HCC cells through the AKT-IKKβ-p65axis. Additionally, the alternative activation and infiltration of tumor-associated macrophages induced by LAIR1 were reliant on the upregulation of IL6 and CCL5 within this axis, respectively. In conclusion, blocking LAIR1 was found to be an effective approach in combating the cancerous advancement of HCC.

NOP2 facilitates EZH2-mediated epithelial–mesenchymal transition by enhancing EZH2 mRNA stability via m5C methylation in lung cancer progression

NOP2, a member of the NOL1/NOP2/SUN domain (NSUN) family, is responsible for catalyzing the posttranscriptional modification of RNA through 5-methylcytosine (m5C). Dysregulation of m5C modification has been linked to the pathogenesis of various malignant tumors. Herein, we investigated the expression of NOP2 in lung adenocarcinoma (LUAD) tissues and cells, and found that it was significantly upregulated. Moreover, lentivirus-mediated overexpression of NOP2 in vitro resulted in enhanced migration and invasion capabilities of lung cancer cells, while in vivo experiments demonstrated its ability to promote the growth and metastasis of xenograft tumors. In contrast, knockdown of NOP2 effectively inhibited the growth and metastasis of lung cancer cells. RNA-sequencing was conducted to ascertain the downstream targets of NOP2, and the findings revealed a significant upregulation in EZH2 mRNA expression upon overexpression of NOP2. Subsequent validation experiments demonstrated that NOP2 exerted an m5C-dependent influence on the stability of EZH2 mRNA. Additionally, our investigations revealed a co-regulatory relationship between NOP2 and the m5C reader protein ALYREF in modulating the stability of EZH2 mRNA. Notably, the NOP2/EZH2 axis facilitated the malignant phenotype of lung cancer cells by inducing epithelial–mesenchymal transition (EMT) both in vitro and in vivo. Mechanistically, ChIP analysis proved that EZH2 counteracted the impact of NOP2 on the occupancy capacity of EZH2 and H3K27me3 in the promoter regions of E-cadherin, a gene crucial for regulating EMT. In a word, our research highlights the significant role of NOP2 in LUAD and offers novel mechanistic insights into the NOP2/ALYREF/EZH2 axis, which holds promise as a potential target for lung cancer therapy.

Burned-Out Testicular Carcinoma Presenting as Inferior Vena Cava Tumor Thrombus With Pulmonary Tumor Embolism on FDG PET/CT: A Case Report.

"Burned-out" testicular tumor is a very rare clinical phenomenon, which refers to the presence of a metastatic germ cell tumor with no clinical findings in the testicle due to spontaneous regression of the primary testicular lesion. We present an unusual case of burned-out testicular embryonal germ cell carcinoma presenting as an extensive inferior vena cava tumor thrombus with malignant pulmonary embolism in which FDG PET/CT played a pivotal role in detecting the extent and significance of the disease.

Complete Favorable Response after Second-Line Immunotherapy in Stage IV Non-Small Lung Cancer with Visceral Metastases and Operated Brain Metastasis

Introduction: Patients with non-small cell lung cancer (NSCLC) and brain metastatic disease have an unfavorable prognosis. The goal of the treatment in stage IV NSCLC is to increase the survival rate and to improve the quality of life. Case report: We present the case of a young male patient (47 years old at the time of diagnosis in 2021) with NSCLC stage IV with the onset of the disease through neurological symptoms determined by brain metastasis. The immunohistochemical result raised problems of differential diagnosis. The complete favorable response was obtained 20 months after the initiation of second-line immunotherapy, maintaining this response 6 months later. Discussion: The therapeutic approach for the second-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) without mutations has been revolutionized by the approval of immune-checkpoint inhibitors (ICIs). The combination of radiotherapy and immunotherapy can increase the abscopal phenomenon by the stimulation of an immune response against tumors at distant sites, outside the radiation field, as recent studies suggest. Conclusions: Second-line immunotherapy is beneficial to the survival of patients with NSCLC with disease progression beyond initial chemotherapy. The combination of radiotherapy and immunotherapy has the potential to play an important role in metastatic NSCLC.

M6A reader IGF2BP2 promotes M2 macrophage polarization and malignant biological behavior of bladder cancer by stabilizing NRP1 mRNA expression

BackgroundInsulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) has been confirmed to play oncogenic role in many cancers. However, the role and mechanism of IGF2BP2 in bladder cancer (BCa) still deserves to be further revealed.MethodsThe mRNA and protein levels of IGF2BP2 and neuronilin-1 (NRP1) were detected by real-time quantitative PCR (RT-qPCR) and western blot. Cell proliferation, apoptosis, migration and invasion were determined using colony formation assay, EdU assay, CCK8 assay, flow cytometry and transwell assay. Xenograft tumor model was conducted to evaluate the role of IGF2BP2 in vivo. THP-1-M0 macrophages were co-cultured with the condition medium (CM) of BCa cells to induce polarization. M2 macrophage polarization was assessed by detecting the mRNA levels of M2 macrophage markers using RT-qPCR and measuring the proportion of M2 macrophage markers using flow cytometry. Moreover, MeRIP and RIP assay were performed to assess m6A level and the interaction between IGF2BP2 and NRP1.ResultsIGF2BP2 and NRP1 were upregulated in BCa tissues and cells. IGF2BP2 knockdown suppressed BCa cell growth and metastasis, as well as inhibited BCa tumor growth. After THP-1-M0 macrophages were co-cultured with the CM of BCa cells, the levels of M2 macrophage markers were markedly enhanced, while this effect was abolished by IGF2BP2 knockdown. IGF2BP2 level was positively correlated with NRP1 level, and it could increase NRP1 mRNA stability. NRP1 overexpression reversed the suppressive effect of IGF2BP2 knockdown on M2 macrophage polarization and BCa cell progression.Conclusionm6A-reader IGF2BP2 enhanced M2 macrophage polarization and BCa cell progression by promoting NRP1 mRNA stability.

Research progress on anti-cancer mechanism of salidroside regulating miRNA-mRNA signaling axis

Abstract MiRNA (MicroRNA) can target and regulate mRNA, thereby influencing the biological processes of tumors. The extract of Tibetan medicine Rhodiola demonstrates anti-tumor effects by targeting and regulating cancer-related signaling molecules and pathways. This review aims to pave the way for integrating salidroside into clinical practice, fully leverage its multi-effective and multi-targeted biological effects, and innovate approaches to tumor prevention and management, thus enhancing cancer prognosis. We initially delve into the occurrence and mechanism of action of miRNA, as well as the anti-tumor mechanism of the miRNA-mRNA signaling axis. Additionally, it was described that salidroside can hinder cancer cell proliferation by inducing autophagy and apoptosis, inhibiting cell metastasis and invasion, and modulating the tumor microenvironment and cell cycle. Moreover, examples from lung cancer, gastric cancer, and nasopharyngeal carcinoma confirm that salidroside regulates the onset and progression of tumors through the miRNA-mRNA signaling axis. This groundbreaking discovery carries significant implications for cancer diagnosis and treatment, offering a novel pathway for therapeutic intervention.

Weekly paclitaxel, carboplatin and cetuximab (PCC) combination followed by nivolumab in platinum-sensitive recurrent and /or metastatic squamous cell carcinoma of head and neck: a retrospective analysis from two institutions in India

Background: First line (1L) TP-Ex-like regimen followed by 2nd-line (2L) immunotherapy represents one of the standards of care in platinum-sensitive recurrent and/or metastatic squamous cell carcinoma of head and neck (R/M SCCHN). We report our experience from 2 tertiary care institutions of India. Methods: This is a retrospective analysis of consecutive patients of platinum-sensitive R/M SCCHN treated with 1L weekly paclitaxel, carboplatin, and cetuximab (PCC) regimen followed by cetuximab maintenance (if non-progressive) or 2L nivolumab or oral metronomic chemotherapy (OMCT) on progression. Overall response rates (ORR), progression-free survival after 1L and 2L (PFS-1 & PFS-2), overall survival (OS), and safety were evaluated. Results: The study included 54 patients; median age 56.5 years; 89% men; 11% had cardiac dysfunction; 13% had renal dysfunction. After 1L PCC, ORR was 59.3%; median PFS-1 was 7.031 months; 61% had progression; 35% were treated with nivolumab and 18% with OMCT. The ORR was 26.3% (nivolumab) and 10% (OMCT). Median PFS-2 was 6.5 months (nivolumab) and 2 months (OMCT). The median OS was 15.01 months (entire cohort), 20.6 months (nivolumab), and 7 months (OMCT). Grade III/IV adverse events on PCC included neutropenia (31.4%), anaemia (35.1%), thrombocytopenia (7.4%), febrile neutropenia (11.1%), and skin reaction (16.6%); no Grade-III/IV treatment-related toxicities on 2L. Conclusions: 1L weekly PCC is an effective regimen for palliative therapy of platinum- sensitive R/MSCCHN with an acceptable toxicity profile. The addition of 2L nivolumab on progression further improves the outcomes.

RAD51B-AS1 promotes the malignant biological behavior of ovarian cancer through upregulation of RAD51B.

Long non-coding RNAs (lncRNAs) play an indispensable role in the occurrence and development of ovarian cancer (OC). However, the potential involvement of lncRNAs in the progression of OC is largely unknown. To investigate the detailed roles and mechanisms ofRAD51 homolog B-antisense 1 (RAD51B-AS1), a novel lncRNA in OC, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to verify the expression of RAD51B-AS1. Cellular proliferation, metastasis, and apoptosis were detected using the cell counting kit-8 (CCK-8), colony-formation, transwell, and flow cytometry assays. Mouse xenograft models were established for the detection of tumorigenesis. The results revealed that RAD51B-AS1 was significantly upregulated in a highly metastatic human OC cell line and OC tissues. RAD51B-AS1 significantly increased the proliferation and metastasis of OC cells and enhanced their resistance to anoikis. Biogenetics prediction analysis revealed that the only target gene of RAD51B-AS1 was RAD51B. Subsequent gene function experiments revealed that RAD51B exerts the same biological effects as RAD51B-AS1. Rescue experiments demonstrated that the malignant biological behaviors promoted by RAD51B-AS1 overexpression were partially or completely reversed by RAD51B silencing in vitro and in vivo. Thus, RAD51B-AS1 promotes the malignant biological behaviors of OC and activates the protein kinase B (Akt)/B cell lymphoma protein-2 (Bcl-2) signaling pathway, and these effects may be associated with the positive regulation of RAD51B expression. RAD51B-AS1 is expected to serve as a novel molecular biomarker for the diagnosis and prediction of poor prognosis in OC, and as a potential therapeutic target for disease management.

Pregnancy and Unilateral Krukenberg Tumour: Factual or Fictious – A Case Report

Krukenburg tumor, a secondary ovarian neoplasm, arises from various primary sites. It’s occurrence during pregnancy is extremely rare. We are reporting the case of a 24 year old G2P1L1 lady with a unilateral Krukenberg tumor diagnosed in first trimester of pregnancy. The case posed as a diagnostic challenge as the presentation is non-specific and radiological diagnosis is very challenging owing to the similarity of the tumour to ectopic pregnancy on imaging. The sparsity of data and unique presentation of the patient inspired us to write this report. This is a 24 year old lady who presented to the emergency department with the complaints of amenorrhea for 2 months, pain abdomen and bleeding per vaginum for 2 days. Urine Pregnancy Test done at home was positive. She was found to be in shock and was resuscitated. Ultrasonography done showed a possibility of an ectopic pregnancy with rupture or a partial molar pregnancy. She was taken up for emergency laparotomy, a lobulated, irregular right sided ovarian mass suggestive of a right ovarian neoplasm with a normal left ovary and an intrauterine incomplete abortion was found. She underwent right salpingo-oophorectomy along with the ovarian mass; with stepwise exploration of pelvis and abdomen followed by dilatation and curettage for the evacuation of the retained product of conception. Histopathological examination revealed features suggestive of metastatic Signet Ring Cell Carcinoma. Further investigation with CECT chest, abdomen and pelvis and upper GI endoscopy revealed a gastric primary. This case depicts the challenges faced by physicians in correctly diagnosing malignant tumours during pregnancy. By reporting this case, we aim to raise awareness among physicians regarding the need for heightened vigilance and multi-disciplinary approach in order to timely and accurately diagnose such conditions.

Unraveling the noncoding RNA landscape in glioblastoma: from pathogenesis to precision therapeutics.

Glioblastoma (GBM) is an aggressive type IV brain tumor that originates from astrocytes and has a poor prognosis. Despite intensive research, survival rates have not significantly improved. Noncoding RNAs (ncRNAs) are emerging as critical regulators of carcinogenesis, progression, and increased treatment resistance in GBM cells. They influence angiogenesis, migration, epithelial-to-mesenchymal transition, and invasion in GBM cells. ncRNAs, such as long ncRNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are commonly dysregulated in GBM. miRNAs, such as miR-21, miR-133a, and miR-27a-3p, are oncogenes that increase cell proliferation, metastasis, and migration by targeting TGFBR1 and BTG2. In contrast, lncRNAs, such as HOXD-AS2 and LINC00511, are oncogenes that increase the migration, invasion, and proliferation of cells. CircRNAs, such as circ0001730, circENTPD7, and circFOXO3, are oncogenes responsible for cell growth, angiogenesis, and viability. Developing novel therapeutic strategies targeting ncRNAs, cell migration, and angiogenesis is a promising approach for GBM. By targeting these dysregulated ncRNAs, we can potentially restore a healthy balance in gene expression and influence disease progression. ncRNAs abound within GBM, demonstrating significant roles in governing the growth and behavior of these tumors. They may also be useful as biomarkers or targets for therapy. The use of morpholino oligonucleotides (MOs) suppressing the oncogene expression of HOTAIR, BCYRN1, and cyrano, antisense oligonucleotides (ASOs) suppressing the expression of ncRNAs such as MALAT1 and miR-10b, locked nucleic acids (LNAs) suppressing miR-21, and peptide nucleic acids (PNAs) suppressing the expression of miR-155 inhibited the PI3K pathway, tumor growth, angiogenesis, proliferation, migration, and invasion. Targeting oncogenic ncRNAs with RNA-interfering strategies such as MOs, ASOs, LNAs, CRISPR-Cas9 gene editing, and PNA approaches may represent a promising therapeutic strategy for GBM. This review emphasizes the critical role of ncRNAs in GBM pathogenesis, as well as the potential for new therapeutic strategies targeting these pathways to improve the prognosis and quality of life for GBM patients.

Microproteins/micropeptides dysregulation contributes to cancer progression and development: A mechanistic review.

Microproteins, known as micropeptides, are small protein molecules encoded by short open reading frames. These recently identified molecules have been proven to be an essential part of the human proteome that participates in multiple processes, such as DNA repair, mitochondrial respiration, and regulating different signaling pathways. A growing body of studies has evidenced that microproteins exhibit dysregulated expression levels in various malignancies and contribute to tumor progression. It has been reported that microproteins interact with many proteins, such as enzymes (e.g., adenosine triphosphate synthase) and signal transducers (e.g., c-Jun), and regulate malignant cell metabolism, proliferation, and metastasis. Moreover, microproteins have been found to play a significant role in multidrug resistance in vitro and in vivo by their activity in DNA repair pathways. Considering that, this review intended to summarize the roles of microproteins in different aspects of tumorigenesis with diagnostic and therapeutic perspectives.