Impact of Cytoreductive Nephrectomy in the Management of Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Study.

In this study, we aimed to determine the utility of cytoreductive nephrectomy (CN) in real-world clinical practice and investigate whether CN contributes to improved oncological outcomes in patients with metastatic renal cell carcinoma (mRCC). This retrospective multicenter cohort study enrolled patients with mRCC who received systemic therapy at six institutions between May 2005 and May 2023. The patients were divided into those who did not undergo CN (Group I) and those who underwent CN (Group II). The primary endpoints were oncological outcomes, including cancer-specific survival (CSS) and progression-free survival (PFS). Altogether, 137 patients with mRCC were included in this study. The median CSS was 14 months in Group I and 32 months in Group II (p < 0.001). Additionally, the median PFS in Groups I and II was 5 and 13 months, respectively (p = 0.006). A multivariate analysis showed that CN was an independent prognostic factor for CSS and PFS. Hence, CN is a potential treatment modality that can improve oncological outcomes in patients with mRCC.

Thoracoscopic primary repair is useful for esophageal atresia with tracheoesophageal fistula in neonates with low body weight.

PURPOSE: The surgical indication of thoracoscopic primary repair for esophageal atresia with tracheoesophageal fistula is under debate. The current study aimed to investigate the outcome of thoracoscopic primary repair for esophageal atresia with tracheoesophageal fistula in patients weighing < 2000 g and those who underwent emergency surgery at the age of 0 day. METHODS: The surgical outcomes were compared between patients weighing < 2000 g and those weighing > 2000 g at surgery and between patients who underwent surgery at the age of 0 day and those who underwent surgery at age ≥ 1 day. RESULTS: In total, 43 patients underwent thoracoscopic primary repair for esophageal atresia with tracheoesophageal fistula. The surgical outcomes according to body weight were similar. Patients who underwent surgery at the age of 0 day were more likely to develop anastomotic leakage than those who underwent surgery at the age of ≥ 1 day (2 vs. 0 case, p = 0.02). Anastomotic leakage was treated with conservative therapy. CONCLUSION: Thoracoscopic primary repair is safe and useful for esophageal atresia with tracheoesophageal fistula even in newborns weighing < 2000 g. However, emergency surgery at the age of 0 day should be cautiously performed due to the risk of anastomotic leakage.

Targeting dependency on a paralog pair of CBP/p300 against de-repression of KREMEN2 in SMARCB1-deficient cancers.

SMARCB1, a subunit of the SWI/SNF chromatin remodeling complex, is the causative gene of rhabdoid tumors and epithelioid sarcomas. Here, we identify a paralog pair of CBP and p300 as a synthetic lethal target in SMARCB1-deficient cancers by using a dual siRNA screening method based on the "simultaneous inhibition of a paralog pair" concept. Treatment with CBP/p300 dual inhibitors suppresses growth of cell lines and tumor xenografts derived from SMARCB1-deficient cells but not from SMARCB1-proficient cells. SMARCB1-containing SWI/SNF complexes localize with H3K27me3 and its methyltransferase EZH2 at the promotor region of the KREMEN2 locus, resulting in transcriptional downregulation of KREMEN2. By contrast, SMARCB1 deficiency leads to localization of H3K27ac, and recruitment of its acetyltransferases CBP and p300, at the KREMEN2 locus, resulting in transcriptional upregulation of KREMEN2, which cooperates with the SMARCA1 chromatin remodeling complex. Simultaneous inhibition of CBP/p300 leads to transcriptional downregulation of KREMEN2, followed by apoptosis induction via monomerization of KREMEN1 due to a failure to interact with KREMEN2, which suppresses anti-apoptotic signaling pathways. Taken together, our findings indicate that simultaneous inhibitors of CBP/p300 could be promising therapeutic agents for SMARCB1-deficient cancers.

Surgical treatment for pulmonary metastasis from ovarian cancer: a retrospective case series.

BACKGROUND: Distant metastases of ovarian cancer are rarely detected alone. The effectiveness of surgical intervention for pulmonary metastases from ovarian cancer remains uncertain. This study aimed to investigate the clinicopathologic characteristics and outcomes of patients undergoing resection for pulmonary metastasis from ovarian cancer. CASE PRESENTATION: The clinicopathologic characteristics and outcomes of radical surgery for pulmonary metastasis from ovarian cancer were investigated. Out of 537 patients who underwent pulmonary metastasis resection at two affiliated hospitals between 2010 and 2021, four (0.74%) patients who underwent radical surgery for pulmonary metastasis from ovarian cancer were included. The patients were aged 67, 47, 21, and 59 years; the intervals from primary surgery to detection of pulmonary metastasis from ovarian cancer were 94, 21, 36, and 50 months; and the overall survival times after pulmonary metastasectomy were 53, 50, 94, and 34 months, respectively. Three of the four patients experienced recurrence after pulmonary metastasectomy. Further, preoperative carbohydrate antigen (CA) 125 levels were normal in two surviving patients and elevated in the two deceased patients. CONCLUSION: In this study, three of the four patients experienced recurrence after pulmonary metastasectomy, but all patients survived for > 30 months after surgery. Patients with ovarian cancer and elevated CA125 levels may not be optimal candidates for pulmonary metastasectomy. To establish appropriate criteria for pulmonary metastasectomy in patients with ovarian cancer, further research on a larger patient cohort is warranted.

Impact of Robotic-Assisted Partial Nephrectomy with Single Layer versus Double Layer Renorrhaphy on Postoperative Renal Function.

We aimed to investigate the differences in renal function between patients who underwent single inner-layer renorrhaphy (SILR) or double-layer renorrhaphy (DLR) among those with renal tumors who underwent robot-assisted partial nephrectomy (RAPN). This retrospective multicenter cohort study was conducted between November 2018 and October 2023 at two institutions and included patients who underwent RAPN. In total, 93 eligible patients who underwent RAPN were analyzed. Preoperative renal function and prevalence of chronic kidney disease were not significantly different between the two groups. Although urinary leakage was observed in three patients (5.9%) in the SILR group, there was no significant difference between the two groups regarding surgical outcomes (p = 0.249). Serum creatinine levels after RAPN were significantly lower in the SILR group than in the DLR group on postoperative days 1 and 365 following RAPN (p = 0.04). The estimated glomerular filtration rate (eGFR) was significantly lower in the DLR group than in the SILR group only on postoperative day 1; however, there was no significant difference between the two groups thereafter. Multivariate analysis showed that the method of renorrhaphy was not a predictor for maintaining renal function after RAPN even though it was associated with eGFR on postoperative day 1.

Discrepancy in the Location of Prostate Cancer Indicated on Biparametric Magnetic Resonance Imaging and Pathologically Diagnosed Using Surgical Specimens.

Accurate diagnosis of the localization of prostate cancer (PCa) on magnetic resonance imaging (MRI) remains a challenge. We aimed to assess discrepancy between the location of PCa pathologically diagnosed using surgical specimens and lesions indicated as possible PCa by the Prostate Imaging Reporting and Data System on MRI. The primary endpoint was the concordance rate between the site of probable clinically significant PCa (csPCa) identified using biparametric MRI (bpMRI) and location of PCa in the surgical specimen obtained using robot-assisted total prostatectomy. Among 85 lesions identified in 30 patients; 42 (49.4%) were identified as possible PCa on MRI. The 85 PCa lesions were divided into positive and negative groups based on the bpMRI results. None of the patients had missed csPCa. Although the diagnostic accuracy of bpMRI was relatively high for PCas located in the middle of the prostate (p = 0.029), it was relatively low for PCa located at the base of the prostate, all of which were csPCas. Although current modalities can accurately diagnose PCa, the possibility that PCa is present with multiple lesions in the prostate should be considered, even if MRI does not detect PCa.

Prognostic factors in pulmonary metastases resection from colorectal cancer: impact of right-sided colon cancer and early recurrence.

OBJECTIVE: This retrospective cohort study aimed to explore the surgical outcomes and prognostic factors of resection of pulmonary metastases (PM) from colorectal cancer (CRC). METHODS: Overall, 60 patients who underwent resection of PM from CRC between 2015 and 2021 at two institutions were reviewed. The primary outcome were overall survival (OS) and early recurrence after PM resection. The association between OS and right-sided colon cancer (RCC) was investigated. Early recurrence after PM resection was defined as recurrence within one year. RESULTS: The 5-year OS after CRC resection was 83.8% (95% confidence interval [CI] 67.5-92.4) and after PM resection was 69.4% (95% CI 47.5-83.6). In total, 25 patients had recurrence after PM resection (16 within 1 year and 9 after 1 year). In multivariable analysis for OS, RCC (hazard ratio [HR] 4.370, 95% CI 1.020-18.73; p = 0.047) and early recurrence after resection of PM (HR 17.23, 95% CI 2.685-110.6; p = 0.003) were risk factors for poor OS. In multivariable analysis for early recurrence after PM resection, higher value of carcinoembryonic antigen (CEA) (> 5.0 mg/dL) before PM resection was a risk factor for early recurrence (HR 3.275, 95% CI 1.092-9.821; p = 0.034). CONCLUSION: The RCC and early recurrence after PM resection were poor prognosis factors of OS. Higher value of CEA before PM resection was an independent risk factor for early recurrence after resection of PM. Comparitive study between surgery and nonsurgery is necessary in patients with higher CEA values.

Effects of trastuzumab emtansine on canine urothelial carcinoma cells in vitro and in vivo.

Urothelial carcinoma (UC) is the most common malignancy of the urinary tract in dogs and has aggressive behaviour. Although human epidermal growth factor receptor 2 (HER2) is a known therapeutic target with evidence in canine UC, the efficacy of anti-HER2 antibody drugs remains unknown. This study aimed to investigate the effects of anti-HER2 antibody drugs including trastuzumab and trastuzumab emtansine (T-DM1) on canine UC cell lines in vitro and in vivo. Four canine UC cell lines (Nene, TCCUB, Love, and Sora) were used. In western blotting, HER2 protein expression was observed in all the cell lines. Although both trastuzumab and T-DM1 showed dose-dependent growth inhibitory activity in the cell lines, T-DM1 showed much stronger activity than that of trastuzumab. In flow cytometry analyses with the canine UC cell line (Sora), T-DM1 but not trastuzumab significantly increased the percentages of early and late apoptotic cells in annexin V apoptotic assays and the sub-G1 phase fraction in cell cycle analyses. For the in vivo experiment, the canine UC cells (Sora) were subcutaneously injected into nude mice. Four days after inoculation, trastuzumab, T-DM1, or vehicle was administered intraperitoneally once a week for three times. Tumour volumes were significantly smaller in the T-DM1 group compared to the trastuzumab and vehicle control groups. These findings indicate that T-DM1 exerts a stronger antitumour effect than that of trastuzumab on canine UC cells in vitro and in vivo, possibly by inducing apoptosis due to DM1.

Upregulation and functional roles of miR-450b in canine oral melanoma.

Canine oral melanoma (COM) is a common and highly aggressive disease with the potential to model human melanomas. Dysregulated microRNAs represent an interesting line of research for COM because they are implicated in tumor progression. One example is miR-450b, which has been investigated for its molecular mechanisms and biological functions in multiple human cancers, but not human or canine melanoma. Here, we aimed to investigate miR-450b as a potential diagnostic biomarker of COM and its functional roles in metastatic and non-metastatic forms of the disease. We investigated the expression of miR-450b and its target mRNA genes in clinical (tumor tissue and plasma) samples and metastatic and primary-tumor cell lines. Knockdown and overexpression experiments were performed to determine the influence of miR-450b on cell proliferation, migration, colony formation, and apoptosis. miR-450b was significantly upregulated in COM and differentiated between metastatic and non-metastatic tumors, and its potential as a biomarker of metastatic and non-metastatic COM was further confirmed in ROC analysis. miR-450b knockdown promoted cell proliferation, migration, and clonogenicity and inhibited apoptosis, whereas its overexpression yielded the reverse pattern. miR-450b directly binds 3' UTR of PAX9 mRNA and modulates its function leading to BMP4 downregulation and MMP9 upregulation at the transcript level. Furthermore, we surmised that miR-450b activates the Wnt signaling pathway based on gene ontology and enrichment analyses. We concluded that miR-450b has the potential as a diagnostic biomarker and could be a target candidate for COM treatment.

A systematic review of Sandifer syndrome in children with severe gastroesophageal reflux.

PURPOSE: Sandifer syndrome (SS), which combines gastroesophageal reflux (GER) and a neurological or psychiatric disorder, is an uncommon condition that often takes a long time to diagnosis. We aimed to systematically review available papers regarding SS. METHODS: After presenting our two cases of SS, we systematically reviewed articles published in MEDILINE/PubMed, Cochrane Library, and Web of Science. RESULTS: The meta-analysis included 54 reported cases and 2 of our own cases. Our results showed that all cases achieved symptom improvement with appropriate treatment for GER. Notably, 19 of the 56 cases exhibited anatomical anomalies, such as hiatal hernia and malrotation. Significantly more patients with than without anatomical anomalies required surgery (p < 0.001). However, 23 of the 29 patients without anatomical anomalies (79%) achieved symptom improvement without surgery. Patients who did not undergo surgery had a median (interquartile range) duration to symptom resolution of 1 (1-1) month. CONCLUSION: The primary care providers should keep SS in the differential diagnosis of patients presenting with abnormal posturing and no apparent neuromuscular disorders. Fundoplication may be effective especially for patients with anatomical anomalies or those whose symptoms do not improve after more than 1 month with nonsurgical treatment.

Duodenal duplication cyst at the second part of the duodenum with congenital duodenal position anomaly completely resected by laparoscopic partial duodenectomy: a case report.

BACKGROUND: Duodenal duplication cysts (DDC) are rare duplications of the alimentary tract. Their treatment depends on their size and location. A radical treatment is total resection, if possible. However, partial excision, puncture, and marsupialization can be selected to prevent surgical injury to the pancreaticobiliary tract despite the risk of recurrence. There are some reports of pancreaticoduodenectomy for DDC because of the risk of recurrent symptoms and malignancy. However, this is considered excessively invasive for DDC, particularly in pediatric cases, because of its extremely low rate of malignancy and high morbidity and mortality rates. We encountered a case of DDC with a congenital duodenal position anomaly occurring in the second part of the duodenum. Taking advantage of the congenital duodenal position anomaly, the DDC was completely resected without injuring the pancreaticobiliary duct. CASE PRESENTATION: A 6-year-old boy was diagnosed with a duodenal duplication cyst with obstruction. There was a congenital duodenal position anomaly. The distal second part of the duodenum was the dorsal side of the proximal second part of the duodenum and ascended upward from the proximal second part of the duodenum. The third and fourth parts of the duodenum ran downward to the left and posterior parts of the portal vein, forming the ligament of Treitz. Complete laparoscopic resection of the duodenal duplication cyst and the second to fourth parts of the duodenum, and duodenojejunostomy with retrocolic reconstruction was performed because the duodenum was easily mobilized to the ligament of Treitz owing to the duodenal position anomaly. The duodenojejunostomy with retrocolic reconstruction achieved a more physiologically normal appearance compared to what would have been achieved with a Roux-en-Y reconstruction. The patient was discharged on postoperative day 12 without any complications. CONCLUSIONS: The procedure used in this case might not be easily applied in all laparoscopy cases. However, it could be an option for duodenal duplication cysts with congenital duodenal position anomalies.

Hypoxia-related Y RNA fragments as a novel potential biomarker for distinguishing metastatic oral melanoma from non-metastatic oral melanoma in dogs.

Hypoxia may promote tumor progression, and hypoxically altered noncoding RNA (ncRNA) expression may play a role in metastasis. Canine oral melanoma (COM) frequently metastasizes, and ncRNA expression under hypoxia may be clinically significant. We aimed to elucidate ncRNA fragments whose expression is altered by hypoxia in COM-derived primary KMeC and metastatic LMeC cell lines using next-generation sequencing to validate these results in qRT-PCR, and then compare expression between metastatic and non-metastatic COM. The NGS analysis and subsequent qRT-PCR validation were performed using hypoxic and normoxic KMeC and LMeC cells, and clinical samples [tumor tissue, plasma, and plasma-derived extracellular vesicles] obtained from dogs with metastatic or non-metastatic melanoma were analyzed with qRT-PCR. Y RNA was significantly decreased in metastatic LMeC cells versus primary KMeC cells in hypoxic and normoxic conditions. The expression of Y RNA was decreased in dogs with metastatic melanoma versus those with non-metastatic melanoma for all clinical sample types, reflecting the pattern found with hypoxia. Receiver operating characteristic analysis demonstrated that Y RNA level is a promising biomarker for discriminating metastatic from non-metastatic melanoma in plasma [area under the curve (AUC) = 0.993, p < 0.0001] and plasma-derived extracellular vesicles (AUC = 0.981, p = 0.0002). Overall, Y RNA may be more resistant to hypoxic stress in the metastatic than the non-metastatic state for COM. However, further investigation is required to elucidate the biological functions of Y RNA under hypoxic conditions.

Pan-tumour analysis of COX-2 expression in dogs.

Cyclooxgenase-2 (COX-2) is associated with inflammatory microenvironment and tumour progression. COX-2 expression was reported in canine tumours, and anti-COX treatment showed therapeutic effects in selected tumour types. Currently, direct comparisons between different tumour types or reports were impossible due to varying evaluation protocols. Additionally, COX-2 expression in relatively uncommon tumours were yet to be evaluated. Here, we analysed COX-2 expression across various tumour types in dogs in a consistent protocol, aiming to revisit accumulated evidence in the field and report novel candidate tumours for anti-COX therapy. COX-2 expression in 32 histological types of tumours, which consisted of 347 samples in total, was investigated using immunohistochemistry followed by the Belshaw's method scoring (range: 0-12). More than the half of the samples expressed COX-2 in mast cell tumours, transitional cell carcinoma in the urinary tract, squamous cell carcinoma, liposarcoma, and melanoma, with COX-2 median scores ranging from 1-8. On the other hand, <20% tissues expressed COX-2 in the half of tumour types investigated. Overall COX-2 positive rate was 27%. In conclusion, the results confirmed COX-2 expression in the well-known COX-2-expresing tumour types and suggested novel candidate tumours for anti-COX-2 therapy. At the same time, overall COX-2 expression was low, and inter- and intra-histology heterogeneity was apparent. This study will provide a foundation reference for future research in canine tumours.

Weight loss of 5% or more after lobectomy for lung cancer via minimally invasive approaches is associated with poor prognosis.

INTRODUCTION: We analyzed the association between postoperative weight loss (WL), preoperative body mass index (BMI), and prognosis in patients with lung cancer who underwent lobectomy using minimally invasive approaches. METHODS: Weight change in 325 patients who underwent radical lobectomy for non-small cell lung cancer was assessed at 3, 6, and 12 months postoperatively and compared to preoperative weight. Patients were divided into three groups according to their preoperative BMI interquartile range: low BMI ≤20.3 kg/m2 , middle BMI 20.4-24.4 kg/m2 , and high BMI ≥24.5 kg/m2 . Postoperative WL ≥5% was evaluated with reference to frailty. RESULTS: There were no significant differences in pathological findings, postoperative complications, or postoperative hospital stay among the three groups. Thirty all-cause deaths and 39 cancer recurrences occurred. Within the first year after surgery, WL of any grade was observed in 229 patients (70.5%) and WL ≥5% in 86 patients (26.5%). Postoperative WL of any grade within 1 year after surgery was not associated with OS and RFS (both p > .05). However, WL ≥5% within 1 year after surgery was associated with worse OS and RFS (p = .007 and .006, respectively). WL ≥5% within 1 year after surgery was more common in the low BMI group (p = .045). There was no difference in OS and RFS among the BMI groups in patients with WL ≥5% and those without WL ≥5% (all p > .05). CONCLUSION: WL ≥5% was associated with poor prognosis after lobectomy via minimally invasive approaches. Weighing is a useful prognostic marker that can be easily self-checked.

Laparoscopic Fundoplication in Patients with Ventriculoperitoneal Shunts: A Systematic Review and Our Experience.

Background: Data on the outcomes of laparoscopic fundoplication (LF) in patients with ventriculoperitoneal (VP) shunts are limited. Materials and Methods: We retrospectively evaluated the demographic characteristics and outcomes of patients who underwent LF at our institutions between 2014 and 2022. Then, we systematically reviewed articles in MEDILINE/PubMed, Cochrane Library, and Web of Science. Results: There was no significant difference in terms of the outcomes between patients with VP shunt (n = 10) and those without (n = 96) at our institutions. None of the patients presented with shunt trouble after LF. The meta-analysis included four retrospective studies and our institutional data. In total, 605 patients (55 with VP shunt) underwent LF. Furthermore, 2 (3.6%) of 55 patients (1 with infection and 1 with occlusion) had shunt troubles. The conversion and complication rates, operative time, and length of hospital stay did not significantly differ between patients with VP shunt and those without. Conclusions: LF can be safely performed on children with VP shunts and is associated with a low risk of shunt troubles. The Clinical Trial Registration number is 2022-387.

Update on aortopexy and posterior tracheopexy for tracheomalacia in patients with esophageal atresia.

Despite improving the survival after repair of esophageal atresia (EA), the morbidity of EA repair remains high. Specifically, tracheomalacia (TM) is one of the most frequent complications of EA repair. Continuous positive airway pressure is generally applied for the treatment of TM. However, surgical intervention is required against an apparent life-threatening event or inability to perform extubation for a long period. According to our review, most cases of TM showed symptom improvement after aortopexy. The ratio of the trachea's lateral and anterior-posterior diameter at the brachiocephalic artery crossing the trachea, which reflects the compression of the trachea by the brachiocephalic artery, is a good indicator of aortopexy. Our finding suggests that most TM cases associated with EA may not be caused by tracheal fragility alone, but may involve blood vessel compression. Posterior tracheopexy (PT) is also an effective treatment for TM. Recently, open or thoracoscopic PT was able to be performed simultaneously with EA repair. In many cases, aortopexy or PT is a safe and effective surgical treatment for TM with EA. Other surgical procedures, such as external stenting, should be considered for patients with diffuse-type TM for whom aortopexy and PT appear relatively ineffective.

Surgical Strategies for Neonates with Prenatally Diagnosed Congenital Biliary Dilatation.

BACKGROUND: This study aimed to develop a postnatal treatment strategy for infants with prenatally diagnosed congenital biliary dilatation. METHODS: We performed a retrospective study of patients with prenatal diagnosed congenital biliary dilatation (CBD), aged <1 year who underwent surgery at our hospital between 2013 and 2023. We classified the patients into two groups, the "early group," consisting of patients who could not wait for growth, and required early surgery, and the "scheduled group," consisting of patients who were asymptomatic and could undergo scheduled surgery, and compared them. The parameters for early surgical prediction were AST, ALT, TB, DB, and CRP levels at birth, 1 week, 2 weeks, 1 month, 2 months, and 3 months after birth, and immediately before surgery, as well as the cyst diameter, presence of intrahepatic bile duct dilation, and presence of debris in the common bile duct. RESULTS: During the study period, 15 patients were diagnosed prenatally. The cyst diameter was significantly larger at all points in the early group. Patients with a cyst diameter of >30 mm at birth, intrahepatic bile duct dilatation at birth, and postnatal enlargement of the common bile duct to >30 mm are more likely to develop symptoms early. Blood biochemistry tests showed no significant differences between the two groups. CONCLUSIONS: Patients with a cyst diameter >30 mm in the early postnatal period require careful postnatal management and parents should be counseled regarding the high likelihood of their child needing surgery within the first 3 months of life. LEVEL OF EVIDENCE: Level IV.

SCD1 inhibition enhances the effector functions of CD8+ T cells via ACAT1-dependent reduction of esterified cholesterol.

We previously reported that the inhibition of stearoyl-CoA desaturase 1 (SCD1) enhances the antitumor function of CD8+ T cells indirectly via restoring production of DC recruiting chemokines by cancer cells and subsequent induction of antitumor CD8+ T cells. In this study, we investigated the molecular mechanism of direct enhancing effects of SCD1 inhibitors on CD8+ T cells. In vitro treatment of CD8+ T cells with SCD1 inhibitors enhanced IFN-γ production and cytotoxic activity of T cells along with decreased oleic acid and esterified cholesterol, which is generated by cholesterol esterase, acetyl-CoA acetyltransferase 1 (ACAT1), in CD8+ T cells. The addition of oleic acid or cholesteryl oleate reversed the enhanced functions of CD8+ T cells treated with SCD1 inhibitors. Systemic administration of SCD1 inhibitor to MCA205 tumor-bearing mice enhanced IFN-γ production of tumor-infiltrating CD8+ T cells, in which oleic acid and esterified cholesterol, but not cholesterol, were decreased. These results indicated that SCD1 suppressed effector functions of CD8+ T cells through the increased esterified cholesterol in an ACAT1-dependent manner, and SCD1 inhibition enhanced T cell activity directly through decreased esterified cholesterol. Finally, SCD1 inhibitors or ACAT1 inhibitors synergistically enhanced the antitumor effects of anti-PD-1 antibody therapy or CAR-T cell therapy in mouse tumor models. Therefore, the SCD1-ACAT1 axis is regulating effector functions of CD8+ T cells, and SCD1 inhibitors, and ACAT1 inhibitors are attractive drugs for cancer immunotherapy.

Elevated expression of miR-301a and its functional roles in canine oral melanoma.

miR-301a is one of numerous dysregulated microRNAs (miRNAs) in canine oral melanoma (COM), one of which is miR-301a (upregulated). Its biological role has been described in various human cancer types, including malignant melanoma, but not in COM. Accordingly, in this study, we investigated miR-301a expression in COM in greater detail to ascertain whether it could serve as a diagnostic biomarker, elucidate its functional roles in this cancer, and predict the possible pathways by which it exerts its effects. Relative expression of miR-301a was investigated in clinical oral tissue and plasma samples and COM cell (KMeC and LMeC) lines using qRT-PCR. Knockdown of miR-301a was also validated for KMeC and LMeC cells using qRT-PCR. We performed CCK-8 assays to assess cell proliferation, monolayer wound-healing, and transwell migration assays to assess cell migration, a colony-formation assay to assess clonogenicity, a TUNEL assay and flow cytometry to assess apoptosis-related effects, and gene enrichment analyses to predict possible related pathways. miR-301a was markedly upregulated in COM oral tissue and plasma clinically, suggesting its potential as a diagnostic biomarker for COM diagnosis. In vitro assays demonstrated that miR-301 significantly inhibited apoptosis in COM cells while promoting cell migration, proliferation, and clonogenicity. We also predicted that miR-301 exerts cancer-promoting effects through the Wnt signalling pathway for COM. Our findings suggest that miR-301a is a COM oncomiR that regulates several oncogenic phenotypes with the potential to be a diagnostic biomarker.