Long noncoding RNA HOTAIR regulates the stemness of breast cancer cells via activation of the NF-κB signaling pathway.

Breast cancer is the most prevalent cancer among women, and it is characterized by a high rate of tumor development and heterogeneity. Breast cancer stem cells (CSCs) may well contribute to these pathological properties, but the mechanisms underlying their self-renewal and maintenance are still elusive. Here, we found that the long noncoding RNA HOTAIR is highly expressed in breast CSCs. HOTAIR is required for breast CSC self-renewal and tumor propagation. Mechanistically, we demonstrate that HOTAIR recruits the PRC2 protein complex to the promoter of IκBα to inhibit its expression, leading to activation of the NF-κB signaling pathway. The activated NF-κB signaling promotes downstream c-Myc and Cyclin D1 expression. Furthermore, our analysis of clinical samples from the GEPIA database indicated that the IκBα level, as well as the survival rate of patients, with high HOTAIR expression was significantly lower than that of patients with relatively low HOTAIR expression. Our data suggest that HOTAIR-mediated NF-κB signaling primes breast CSC self-renewal and tumor propagation. In sum, we have identified HOTAIR-based NF-κB signaling regulatory circuit that promotes tumorigenic activity in breast CSCs, further indicating that HOTAIR could be a promising target for clinical treatment of breast cancers.

Intestinal Autotransplantation for Locally Advanced or Locally Recurrent Colon Cancer Invading SMA.

OBJECTIVE: To examine the outcomes of intestinal autotransplantation (IATx) in patients with locally advanced or recurrent colon cancer (LACC or LRCC) invading the superior mesenteric artery (SMA). BACKGROUND: SMA Involvement in LACC or LRCC is deemed unresectable and is associated with a poor prognosis. Combined extended resections of multiple organs together with SMA, followed by IATx may offer favorable clinical outcomes. However, data on its safety and efficacy are scarce. DESIGN: This retrospective cohort study included patients undergoing IATx between May 2018 and December 2022 in intestinal transplant programs at two university-affiliated hospitals in China. Patients with LACC or LRCC concomitantly with SMA contact of more than 180° were included. Patients with a locoregional peritoneal, pelvic, or distal metastasis were excluded. RESULTS: Ten patients underwent either IATx combined with pancreaticoduodenectomy (n=8) or IATx alone (n=2). Eight patients (80%) were male, and the median age was 55 years (range, 32 - 71 y). The Kaplan-Meier estimates for recurrence-free survival and overall survival at 3 years after IATx were 68% and 80%, respectively. No perioperative deaths occurred. All ten patients experienced postoperative complications including Clavien-Dindo grade I (n=1), grade II (n=4), grade IIIa (n=1), grade IIIb (n=3) and grade IVa (n=1), which comprised acute venous thromboses, upper gastrointestinal hemorrhage, anastomotic leak, gastropareses and significant pleural effusions. With an average follow-up of 23.9 months, eight patients (80%) were currently alive without evidence of disease. CONCLUSION: Extended resection for LACC or LRCC invading SMA can be performed safely and is associated with prolonged survival.

Soluble PD-L1: a potential dynamic predictive biomarker for immunotherapy in patients with proficient mismatch repair colorectal cancer.

BACKGROUND: Circulating soluble programmed death ligand 1 (sPD-L1) can negatively regulate T-cell function and serve as a prognostic or predictive marker in a variety of cancers. However, rare studies have evaluated the potential roles of sPD-L1, and no study has estimated its predictive value for the efficacy of immune treatment in colorectal cancer (CRC). METHODS: Plasma samples from 192 CRC patients were used to estimate correlations between clinicopathological features and sPD-L1, secreted PD-L1 (secPD-L1) and exosomal PD-L1 (exoPD-L1). Baseline and posttreatment sPD-L1 levels were also investigated in 55 patients with metastatic CRC (mCRC) treated with chemotherapy ± targeted therapy and 40 patients with proficient mismatch repair (pMMR) mCRC treated with combination immunotherapy. Both sPD-L1 and secPD-L1 were quantified by enzyme-linked immunosorbent assay, while exoPD-L1 was analyzed using flow cytometry. RESULTS: secPD-L1 was the major component and positively correlated with sPD-L1 in CRC, while exoPD-L1 was almost undetectable. Higher levels of sPD-L1 were detected in patients with distant metastasis, especially those with distant lymph node metastasis and tissue combined positive score (CPS) instead of tumor proportion score (TPS). Chemotherapy or targeted therapy did not significantly impact sPD-L1 concentration. Progressive disease on combination immunotherapy was associated with an increase in sPD-L1 level, whereas no significant change was observed in patients with durable clinical benefit. CONCLUSION: sPD-L1 mainly consisted of secPD-L1, and its level was higher in patients with distant metastasis, especially distant lymph node metastasis and positive CPS. sPD-L1 is a potential dynamic marker to identify rapid progression on combination immunotherapy and avoid ineffective treatment for pMMR CRC.

Successful combined auxiliary partial liver and intestinal transplantation in two highly sensitized, cross-match positive patients.

INTRODUCTION: Sensitization to human leukocyte antigen (HLA) creates an immunological barrier to intestinal transplantation (ITx). Current desensitization therapies are limited and ineffective in the most highly sensitized patients. A co-transplanted whole liver transplant can protect a kidney, heart, or intestinal allograft from antibody-mediated injury. Whether an auxiliary partial liver allograft provides effective protection for highly sensitized intestinal transplant recipients is unknown. METHODS: Two patients with strong HLA donor-specific antibody at high titer against their deceased donors underwent combined auxiliary partial liver and ITx across a positive cross-match. The left lateral lobes from the combined-graft recipients and the right liver lobes from the deceased donors were transplanted as a domino procedure to other four patients. RESULTS: Two combined-graft recipients have had an uneventful postoperative course without major complications at a 12- and 24-month follow-up, respectively. Intestinal graft function has been excellent with no evidence of humoral or cellular rejection. While a positive cross-match turned negative, titers of donor-specific HLA antibodies gradually declined over time after transplant. The left liver lobes procured from the combined-graft recipients were successfully transplanted into two pediatric patients (age 1.9, 2.4 years) and the right lobes from two deceased donors were successfully transplanted into two adult patients. All transplant procedures went well, without post-operative complications related to the splitting technique. CONCLUSION: Our results indicate that an auxiliary liver transplant can effectively protect a co-transplanted intestinal allograft against rejection and suggest that this combined procedure may serve as a useful therapeutic adjunct for a highly sensitized intestinal transplant candidate.

Multiple Strategies to Develop Small Molecular KRAS Directly Bound Inhibitors.

KRAS gene mutation is widespread in tumors and plays an important role in various malignancies. Targeting KRAS mutations is regarded as the "holy grail" of targeted cancer therapies. Recently, multiple strategies, including covalent binding strategy, targeted protein degradation strategy, targeting protein and protein interaction strategy, salt bridge strategy, and multivalent strategy, have been adopted to develop KRAS direct inhibitors for anti-cancer therapy. Various KRAS-directed inhibitors have been developed, including the FDA-approved drugs sotorasib and adagrasib, KRAS-G12D inhibitor MRTX1133, and KRAS-G12V inhibitor JAB-23000, etc. The different strategies greatly promote the development of KRAS inhibitors. Herein, the strategies are summarized, which would shed light on the drug discovery for both KRAS and other "undruggable" targets.

Short- and long-term complications after living donor ileal resection.

Intestinal transplantation from deceased donors is the established procedure for patients with irreversible intestinal failure. However, a living-donor intestinal transplant has not been routinely performed yet because of undefined surgical risks to the donor. In this report, we reviewed our experience with living-donor ileal resection from May 1999 to December 2021. A total of 40 living-donor ileal resections were performed for 40 intestinal transplant recipients. Clinical data were prospectively collected and analyzed for postoperative complications after ileal procurement. None of the donors experienced life-threatening complications or mortality. Six (15%) of 40 donors experienced minor operative complications. Transit intestinal graft inadequacy including weight loss, diarrhea, and vitamin B12 deficiency was common early following surgery, but was manageable and disappeared in most cases within a year. All donors had significant reductions in total plasma cholesterol and low-density lipoprotein cholesterol concentrations after donation as compared with the baseline levels. With an average follow-up of 67.8 months, bilateral kidney stones occurred in one donor and gallstones in the other. All the donors have regained their normal capacity for work. Living-donor ileal resection is associated with minimal short- and long-term morbidity and remains an attractive alternative for potential recipients when suitable deceased donors are unavailable.

Living Donor Intestinal Transplantation: Recipient Outcomes.

OBJECTIVE: To examine outcomes of living-donor intestinal transplant (LDITx) recipients. BACKGROUND: LDITx is not routinely performed because of surgical risks to the donor and the potential inferior physiologic performance of the segmental graft. However, data on the effectiveness of LDITx are scarce. DESIGN: This retrospective cohort study included patients undergoing LDITx between May 1999 and December 2021 in intestinal transplant programs in 2 university-affiliated hospitals in China. RESULTS: Actuarial survival rates were 80%, 72.7%, 66.7% for patient and 72.4%, 63.6%, 60% for graft at 1, 3, and 5 years, respectively. Recipients with >3/6 HLA-matched grafts had superior patient and graft survival rates than those with ≤3/6 HLA-matched grafts ( P <0.05). There were 12 deaths among the recipients, with infection being the leading cause (41.7%), followed by rejection (33.3%), surgical complications (16.7%), and others (8.3%). There were 16 graft losses among the recipients, with acute cellular rejection being the predominant cause (37.5%), followed by infection (25%), technical failure (12.5%), chronic rejection (12.5%), and others (12.5%). With an average follow-up of 3.7 (range, 0.6-23) years, the rates of acute and chronic rejection were 35% and 5%, and the rate of cytomegalovirus disease and post-transplant lymphoproliferative disease were 5% and 2.5%, respectively. Of the 40 patients, 28 (70%) are currently alive and have achieved enteral autonomy. CONCLUSIONS: LDITx is a valuable treatment option for patients with end-stage intestinal failure. Improved immunosuppression, better HLA matching, and shorter cold ischemia times were associated with reduced rates of rejection, viral-mediated infection and improved graft survival.

DNMT1-mediated methylation of BEX1 regulates stemness and tumorigenicity in liver cancer.

BACKGROUND & AIMS: Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) both exhibit notable cancer stem cell (CSC) features. Moreover, the development of both diseases is closely associated with the presence of CSCs. We investigated the role of brain-expressed X-linked protein 1 (BEX1) in regulating the CSC properties of HB and a subtype of HCC with high CSC features (CSC-HCC). METHODS: Stemness scores were analyzed in 5 murine HCC models. A subpopulation of BEX1-positive cells and BEX1-negative cells were sorted from HCC cell lines, and subjected to transcriptome analysis. The expression and function of BEX1 was examined via western blotting, sphere formation assays, and xenograft tumor models. RESULTS: We identified BEX1 as a novel CSC marker that was required for the self-renewal of liver CSCs. Furthermore, zebularine, a potent DNMT1 inhibitor, can induce the reactivation of BEX1 by removing epigenetic inhibition. Notably, BEX1 was highly expressed in patients with HB and CSC-HCC, but not in patients with non-CSC HCC. Moreover, DNMT1-mediated methylation of the BEX1 promoter resulted in differential BEX1 expression patterns in patients with HB, CSC-HCC, and non-CSC-HCC. Mechanistically, BEX1 interacted with RUNX3 to block its inhibition of ß-catenin transcription, which led to the activation of Wnt/ß-catenin signaling, and stemness maintenance in both HB and CSC-HCC. In contrast, downregulated BEX1 expression released RUNX3 and inhibited the activation of Wnt/ß-catenin signaling in non-CSC-HCC. CONCLUSION: BEX1, under the regulation of DNMT1, is necessary for the self-renewal and maintenance of liver CSCs through activation of Wnt/ß-catenin signaling, rendering BEX1 a potentially valuable therapeutic target in both HB and CSC-HCC. LAY SUMMARY: Cancer stem cells (CSCs) contribute to a high rate of cancer recurrence, as well as resistance to conventional therapies. However, the regulatory mechanisms underlying their self-renewal remains elusive. Herein, we have reported that BEX1 plays a key role in regulating CSC properties in different types of liver cancer. Targeting BEX1-mediated Wnt/ß-catenin signaling may help to address the high rate of recurrence, and heterogeneity of liver cancer.

Role of Gut Microbiota in the Development and Treatment of Colorectal Cancer.

Human guts harbor abundant microbes that regulate many aspects of host physiology. However, bacterial imbalance or dysbiosis in the gut due to the dietary or environmental changes may cause colorectal cancer (CRC). Increasing studies show that gut microbiota plays an important role in the occurrence and development of CRC, as a result of virulence factors, bacterial metabolites, or inflammatory pathways. In the future, probiotics or targeting the microbiota will probably be a powerful weapon in the battle against CRC. This review seeks to outline the relationship between gut microbiota and the development of CRC as well as the potential mechanisms of microbiota involved in treatment of CRC, so as to provide some references for research on the development, prevention, and treatment of this disease.

Survivin and angiotensin-converting enzyme polymorphisms with risk of colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Colorectal cancer (CRC) is the most common cause of cancer death worldwide. Numerous studies have identified the roles of survivin -31 G/C and angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms in CRC risk; however, the results remain inconclusive. This study was to investigate associations between these two polymorphisms and CRC susceptibility. METHODS: A comprehensive literature search was conducted to collect relevant case-control studies published between 2000 and 2014. The extracted data were statistically analyzed, and the odds ratios (ORs) with 95% confidence intervals (CIs) were employed to estimate the strength of association. RESULTS: A total of 11 studies were included in the meta-analysis. For survivin G/C polymorphism, six articles reported 1,840 cases and 1,804 controls. Overall, we found the frequency of C allele is higher in CRC cases than that in the healthy controls (57.2% vs. 48.0%), and C allele significantly increased the risk of CRC compared to G allele in allele model (OR = 1.46, 95% CI = 1.33-1.60, P < 0.00001). This association was also found in other genetic models (P < 0.00001). Stratified analysis by ethnicity showed significant association in each genetic model among the Asian population. For ACE I/D polymorphism, five studies included 758 cases and 6,755 controls. No significant association was found in any genetic models. CONCLUSIONS: Our results showed that survivin -31 G/C polymorphism might contribute to risk of CRC, especially in the Asian populations. However, the ACE I/D polymorphism is not a genetic factor concerning the risk for CRC. More studies with larger sample sizes are required in the future.

Hand-assisted laparoscopic surgery compared with open resection for mid and low rectal cancer: a case-matched study with long-term follow-up.

BACKGROUND: This study was designed to compare the long-term surgical outcomes of patients with mid and low rectal cancer after open or hand-assisted laparoscopic surgery (HALS). METHODS: A case-matched controlled prospective analysis of 116 patients who underwent hand-assisted laparoscopic surgery (HALS) for stage I to III mid and low rectal cancer from 2005 to 2010 was performed. Contemporary patients who underwent open rectal surgery were matched to the HALS group at the ratio of 1:1. The perioperative clinical outcomes, postoperative pathology, and survival outcomes were compared between the groups. RESULTS: The patient characteristics between the two groups were comparable. Ninety patients in the open group and 85 in the HALS group received sphincter-preserving surgery. HALS resulted in less blood loss and wound infection, faster return to oral diet, shorter postoperative hospital stay, and longer operating time. The two groups had similar complication rates. Lymph node retrieval and involvement of circumferential and distal margins were similar for both procedures. Cumulative incidences of locoregional recurrence, disease-free, or overall survival rates were statistically similar. CONCLUSIONS: This study suggests that HALS for mid and low rectal cancer is acceptable in terms of short-term clinical outcomes and long-term survival results.

Defunctioning cannula ileostomy after lower anterior resection of rectal cancer.

BACKGROUND AND OBJECTIVE: Most surgeons suggest the use of fecal diversion in patients undergoing low anterior resections of rectal tumors at high risk for anastomotic leakage. We describe an exploratory study to evaluate the efficacy and safety of a new diversion method called a spontaneously closing cannula ileostomy, which was designed to protect rectal anastomoses in patients at high risk for anastomotic leakage. The outcomes of patients treated with cannula ileostomy were compared to those of patients treated with loop ileostomy. MAIN OUTCOME MEASURES: Outcomes included the rates of anastomotic leakage, reoperation and other complications, as well as length of hospital stay and cost. DESIGN AND PATIENTS: From January 2011 to December 2012, 294 patients undergoing low colorectal or coloanal anastomosis were treated with ileum diversion using cannula ileostomy or traditional loop ileostomy. Demographics, clinical features, and operational data were recorded. RESULTS: The anastomotic leakage rates were 8.1% (12/149) in the cannula ileostomy group and 8.3% (12/145) in the loop ileostomy group (p = 1.0). The reoperation rate was 3% (4/149) in patients treated with a cannula ileostomy and 3.4% (5/145) in those who underwent a loop ileostomy (p = 0.75). The median length of the hospital stay was 8.6 days in the cannula ileostomy group and 17.1 days (p < 0.01) in the loop ileostomy group, including time for the initial and reversal operations. In the cannula ileostomy group, the median time to defecation from the anus was 16.5 days after the operation. During the follow-up period, 13 patients in the loop ileostomy group retained their stoma, as compared to 2 in the cannula ileostomy group (p < 0.01). LIMITATIONS: This study was a nonrandomized design and lacked contrast enema data to identify anastomotic leaks. CONCLUSIONS: Cannula ileostomy is a safe and effective diverting technique that protects low colorectal and coloanal anastomoses. Patients receiving a cannula ileostomy had shorter hospital stays and lower rates of permanent stoma than those receiving a loop ileostomy.

Reclassification of RAS/BRAF allele mutations predicts the survival benefit of triplet chemotherapy in metastatic colorectal cancer.

Background: Different RAS/BRAF allele mutations imply distinct biological properties in various solid tumors. Recently, several studies have focused on the predictive and prognostic roles of various RAS/BRAF allele mutations in colorectal cancer (CRC) but the results remain controversial. Methods: Between March 2017 and September 2022, the patients diagnosed as stages I-IV CRC with detailed medical records including next-generation sequencing (NGS) data and clinicopathological follow-up information available at our center were enrolled. Survival data were estimated using the Kaplan-Meier method, and the difference was tested in a log-rank test. Multivariate tests were carried out using Cox models. Results: A total of 1029 CRC patients were included, and the incidence of RAS/BRAF mutation was 58.4%. The hypermutated cohort was defined as patients with microsatellite instability-H or POLE/D mutation. In the non-hypermutational cohort, only KRAS G13D mutation was associated with a higher incidence and inferior disease-free survival in patients with stage I-III CRC. In the cohort of patients with non-hypermutated metastatic colorectal cancer (mCRC), we assessed the risk of various RAS/BRAF allele mutations and subsequently reclassified patients into four groups based on first-line median progression-free survival: wild type (group 1), low-risk RAS/BRAF mutation (group 2, RAS/BRAF mutations other than KRAS G13D/G12V/G12C or BRAF V600E), high-risk RAS mutation (group 3, KRAS G13D/G12V/G12C), and BRAF V600E mutation (group 4). mCRC patients with high-risk RAS mutation could significantly benefit from intensive triplet chemotherapy (hazard ratio, 2.54; 95% confidence interval, 1.36-5.12; p = 0.0091). Conclusion: In the non-hypermutated CRC cohort, the prognostic risk of various RAS/BRAF allele mutations varied between local and metastatic CRC. KRAS G13D mutation tended to be the only prognostic marker for stages I-III CRC; however, KRAS G13D/G12V/G12C mutations collectively defined a high-risk subgroup of mCRC patients with poor prognosis, who would benefit from intensive triplet chemotherapy.

Multiple thread ligations versus stapled hemorrhoidopexy on operative outcomes of grade III hemorrhoids: A retrospective cohort study.

Object: Controversy remains regarding the safety and efficacy of hemorrhoid ligation and stapled hemorrhoidopexy (SH) in the treatment of hemorrhoids. The study was to explore the operative outcomes of patients underwent multiple thread ligations (MTL) with SH for the management of grade III hemorrhoids. Methods: This cohort study included patients who underwent MTL (MTL group, 128 cases) or SH (SH group, 141 cases) for grade III hemorrhoids between June 2019 and May 2021. A total of 115 patients in MTL group and 115 patients in SH group were finally included by propensity score matching with a ratio of 1:1. The primary outcome was the recurrence of prolapse within 6 months. Secondary outcomes were operative time, post-operative pain scores, hospital stay, the incidence of complications, Wexner incontinence score, and quality of life of patients with constipation at 6 months post procedure. Results: Multiple thread ligations and SH resulted in comparable recurrence within 6 months of follow-up, with five and seven cases of recurrence, respectively, (P = 0.352). The two groups had comparable outcomes in terms of post-operative pain, hospital stay, Wexner incontinence scores, and constipation-related quality of life (all P > 0.05). The median operative time was 16 min (15-18 min) in the MTL group versus 25 min (16-33 min) in the SH group (P < 0.01). Univariate analysis showed that the MTL technique had a lower risk of postoperative bleeding than that with the SH technique (P < 0.05). Conclusion: The study indicated that the MTL technique might achieve comparable operative outcomes compared with the SH technique for the management of grade III hemorrhoids, nevertheless, MTL seemed to be associated with less risk of surgical bleeding than SH.

Reagentless Electrochemical Detection of Tumor Biomarker Based on Stable Confinement of Electrochemical Probe in Bipolar Silica Nanochannel Film.

The development of simple and probe-integrated aptamer sensors for the electrochemical detection of tumor biomarkers is of great significance for the diagnosis of tumors and evaluation of prognosis. In this work, a probe-integrated aptamer sensor is demonstrated based on the stable confinement of an electrochemical probe in a bipolar nanochannel film, which can realize the reagentless electrochemical detection of the tumor biomarker carcinoembryonic antigen (CEA). To realize the stable immobilization of a large amount of the cationic electrochemical probe methylene blue (MB), a two-layer silica nanochannel array (SNF) with asymmetric charge was grown on the supporting electrode from bipolar SNF (bp-SNF). The inner SNF is negatively charged (n-SNF), and the outer-layer SNF is positively charged (p-SNF). The dual electrostatic interaction including the electrostatic adsorption from n-SNF and the electrostatic repulsion from p-SNF achieve the stable confinement of MB in bp-SNF. The recognitive interface is fabricated by the covalent immobilization of the CEA aptamer on the outer surface of bp-SNF, followed by the blocking of non-specific binding sites. Owing to the stable and abundant immobilized probes and highly specific aptamer interface, the developed aptamer sensor enables the sensitive detection of CEA in the range of 1 pg/mL to 1 µg/mL with a low limit of detection (LOD, 0.22 pg/mL, S/N = 3). Owing to the high selectivity and stability of the developed biosensor, reagentless electrochemical detection of CEA in serum was realized.

Metastatic sites and lesion numbers cooperated to predict efficacy of PD-1 inhibitor-based combination therapy for patients with metastatic colorectal cancer.

BACKGROUND: Limited data have been used to evaluate the efficacy of immunotherapy in metastatic colorectal cancer (mCRC). Furthermore, potential markers that can be used to identify responding patients and to further improve efficacy have not been fully explored. METHODS AND RESULTS: In our study, we included a total of 97 patients with mCRC, who each received programmed death-1 (PD-1) inhibitor-based combination therapy at our center. All 12 hypermutated patients benefited from immunotherapy, with median progression-free survival (mPFS) reaching 28.3 months, regardless of liver metastasis. The objective response rate (ORR) of non-hypermutated patients was 16.5% (14/85), with an mPFS of 4.0 months. For non-hypermutated patients, multivariate analysis revealed that the combination of liver metastasis and baseline lesion number significantly stratified response and survival. The lesion-based analysis indicated that the lymph node was the most responsive, followed by the peritoneum and lung, with liver metastasis being the least responsive. None of the patients (0/7) with negative programmed ligand-1 (PD-L1) expression responded, and positive PD-L1 expression may serve as a biomarker (mPFS 5.7 vs. 2.2 months, p = 0.002) that can be used to further guide treatment in non-hypermutated mCRC with liver metastasis (CRLMs). CONCLUSION: Patients with hypermutated mCRC benefited significantly from immunotherapy, whereas the non-hypermutated cohort with liver metastasis and numerous lesions showed less benefit. The lesion sites reflected varying levels of efficacy, among which PD-L1 potentially cooperated to guide the immunotherapy of CRLMs.

Modified natriuretic peptides and their potential roles in cancer treatment.

The natriuretic peptide family (NPs) is a group of natural endocrine hormones, containing a 17-amino acid ring structure connected by disulfide bonds of two cysteines. In this review, the members of the natriuretic peptide family and their corresponding receptors as well as the anti-cancer effects are introduced. Four cardiac hormones of NPs (ANP, VD, KP and LANP) can effectively inhibit the growth of human small cell lung cancer, breast cancer and other tumors and significantly reduce tumor volume in vivo. The in vitro experiments also show that cardiac hormones, CNP and urodilatin can effectively inhibit the growth of most tumor cells. We then further summarized the anti-cancer mechanism of natriuretic peptides. Finally, we introduce several methods that modify natriuretic peptides, leading to enhance their stability and prolong the biological effects of these peptides, which might be helpful for the clinical application in the future. Peptide therapy is a very promising field for cancer treatments since they can induce the death of cancer cells without dramatically affecting normal cells. The synthesis of a useful and stable natriuretic peptide can enhance the effect of cancer treatments and significantly reduce drug resistance and toxicity.

The complete chloroplast genome sequence of the water fern Ceratopteris thalictroides (Pteridaceae).

This work determined and analyzed the complete chloroplast genome sequence of Ceratopteris thalictroides (Linnaeus) Brongniart 1822 (Pteridaceae). The results indicate that the total chloroplast genome size of C. thalictroides is 149,399 bp in length, and the genome contains a large single-copy (LSC) region of 83,580 bp, a small single-copy (SSC) region of 21,241 bp, and a pair of inverted repeat (IR) regions of 22,289 bp. The GC content of C. thalictroides is 36.7%. The genome encodes a total of 131 unique genes, including 82 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. The phylogenetic analysis results strongly suggest that C. thalictroides is closely related to C. cornuta.

Genomic and transcriptomic analysis of MSI-H colorectal cancer patients with targetable alterations identifies clinical implications for immunotherapy.

Introduction: Targetable alterations such as BRAFV600E mutation and NTRK fusion are enriched in microsatellite instability-high (MSI-H) colorectal cancer (CRC). MSI-H with targetable alterations (MSI-H altered) might present unique opportunities for both targeted therapy and immunotherapy. We systematically evaluated the molecular characteristics and immune-related features of MSI-H altered and MSI-H without targetable alterations (MSI-H wt) CRC patients in our study. Methods: Among 1938 continuously enrolled CRC patients, 126 patients with MSI-H status (6.50%) were included in this retrospective study. Genomic and transcriptomic data were investigated by next-generation sequencing (NGS) and gene expression profiling (GEP), respectively. Results: BRAFV600E, NTRK1, and FGFR2 mutations were the most frequent targetable alterations in MSI-H CRC patients. The MSI-H altered phenotype was significantly associated with older age (p< 0.001), right side (p=0.024) and females (p= 0.036). No lynch syndrome (LS) patients were identified in MSI-H altered group. The tumor mutational burden (TMB), and tumor neoantigen burden (TNB) of MSI-H altered and wt subgroups were comparable (p<0.05). Subsequently, transcriptomic study analysis further revealed MSI-H altered CRC patients were linked to an immune-active tumor microenvironment with higher levels of Teff IFN-gamma, CYT, and MERCK 18 signatures, and lower levels of the IPRES gene signature, EMT and TGF Beta signatures. In addition, case study supported MSI-H CRC patient harboring targetable alterations might also achieved a long-term disease-free survival benefit from immunotherapy. Discussion: Our study preliminary revealed MSI-H altered as a novel subtype of MSI-H CRC patients with unique molecular signatures and immune-active tumor microenvironment. Given the accessibility of immune checkpoint inhibitors (ICIs) treatment, our results might provide clinical evidence for immunotherapy in MSI-H CRC patients with targetable alterations.

Corrigendum: Phylogeny and Taxonomy on Cryptic Species of Forked Ferns of Asia.

[This corrects the article DOI: 10.3389/fpls.2021.748562.].