Neoadjuvant camrelizumab plus apatinib for locally advanced microsatellite instability-high or mismatch repair-deficient colorectal cancer (NEOCAP): a single-arm, open-label, phase 2 study.

Background: PD-1 blockade is highly efficacious for mismatch repair-deficient colorectal cancer in both metastatic and neoadjuvant settings. We aimed to explore the activity and safety of neoadjuvant therapy with PD-1 blockade plus an angiogenesis inhibitor and the feasibility of organ preservation in patients with locally advanced mismatch repair-deficient colorectal cancer.

Methods: We initiated a single-arm, open-label, phase 2 trial (NEOCAP) at Sun Yat-sen University Cancer Center and the Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China.

Long-term outcomes of intraoperative chemotherapy with 5-FU for colorectal cancer patients receiving curative resection (IOCCRC): a randomized, multicenter, prospective, phase III trial.

Background: The authors aimed to compare combined intraoperative chemotherapy and surgical resection with curative surgical resection alone in colorectal cancer patients.

Methods: The authors performed a multicenter, open-label, randomized, phase III trial. All eligible patients were randomized and assigned to intraoperative chemotherapy and curative surgical resection or curative surgical resection alone (1:1).

Long-Term Outcomes of dMMR/MSI-H Rectal Cancer Treated With Anti-PD-1-Based Immunotherapy as Curative-Intent Treatment.

Background: Neoadjuvant anti-PD-1 therapy has shown encouraging efficacy in patients with deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer (LARC), which suggests its potential as a curative-intent therapy and a promising treatment option for organ preservation. We aimed to investigate the long-term outcomes of patients with dMMR/MSI-H LARC who experienced clinical complete response (cCR) after anti-PD-1 therapy.

Methods: We retrospectively analyzed patients with dMMR/MSI-H LARC who achieved cCR and received nonoperative management following neoadjuvant anti-PD-1-based treatment from 4 Chinese medical centers.

The effects of oxaliplatin-based adjuvant chemotherapy in high-risk stage II colon cancer with mismatch repair-deficient: a retrospective study.

Background: For high-risk stageIImismatch repair deficient (dMMR) colon cancers, the benefit of adjuvant chemotherapy remains debatable. The principal aim of this study was to evaluate the prognostic value of high-risk factors and the effect of oxaliplatin-based adjuvant chemotherapy among dMMR stageIIcolon cancers.

Methods: Patients with stage II dMMR colon cancers diagnosed between June 2011 and May 2018 were enrolled in the study.

A novel screening method of DNA methylation biomarkers helps to improve the detection of colorectal cancer and precancerous lesions.

Background: Colorectal cancer (CRC) is one of the most common malignancies, and early detection plays a crucial role in enhancing curative outcomes. While colonoscopy is considered the gold standard for CRC diagnosis, noninvasive screening methods of DNA methylation biomarkers can improve the early detection of CRC and precancerous lesions.

Methods: Bioinformatics and machine learning methods were used to evaluate CRC-related genes within the TCGA database.

Efficacy of PD-1 inhibitors for colorectal cancer and polyps in Lynch syndrome patients.

Background: Programmed death-1 (PD-1) inhibitor is effective for colorectal cancer (CRC) with deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H). We aimed to explore its effects on CRCs and colonic polyps in Lynch syndrome (LS) patients.

Methods: LS patients with CRC who had evaluable tumours and received at least 2 cycles of PD-1 inhibitors were retrospectively included.

Tumor-derived lactate promotes resistance to bevacizumab treatment by facilitating autophagy enhancer protein RUBCNL expression through histone H3 lysine 18 lactylation (H3K18la) in colorectal cancer.

Bevacizumab plays an important role in the first and second line treatment for metastatic colorectal cancer (CRC). And induction of hypoxia and the tumors response to it plays an important role in determining the efficacy of antiangiogenic therapy while the connection between them remains unclear. Here, we found that lactate accumulated in the tumor environment of CRC and acted as substrates for histone lactylation, and this process was further induced by cellular enhanced glycolysis in hypoxia.

Cobalt/Rhodium-Catalyzed Diversified Amidation of Benzocyclobutenols via C-C Cleavage under Catalyst and Condition Control.

Cobalt(III) and rhodium(III)-catalyzed regio- and chemoselective amidation of benzocyclobutenols has been realized using dioxazolone as the amidating reagent to afford three classes of C-N-coupled products via β-carbon elimination of the benzocyclobutenol. The Co(III)-catalyzed coupling initially afforded an isolable -(-acylamino)arylmethyl ketone, which could further cyclize to the corresponding indole derivatives under condition control. In contrast, efficient stepwise diamidation has been achieved under Rh(III) catalyst control.

Three-component regioselective carboamidation of 1,3-enynes rhodium(III)-catalyzed C-H activation.

Rhodium-catalyzed regio- and stereoselective three-component carboamidation of 1,3-enynes has been realized using indoles and dioxazolones as the functionalizing reagents. A wide range of multi-substituted skipped 1,4-dienes have been constructed in good yields and excellent stereoselectivity. The stereoselectivity is under substrate control.

The apolipoprotein B and apolipoprotein A-I Ratio serves as a strong prognostic factor for the overall survival of patients with colorectal cancer.

Background: The lipid metabolism status of patients with colorectal cancer (CRC) has not been understood comprehensively. The present study investigated the characteristics of lipid metabolism parameters in CRC patients with or without metastases and identified the independent prognostic factors of long-term prognosis.

Methods: The clinicopathological data of 231 CRC patients along with 259 formalin-fixed paraffin-embedded samples with or without liver or lung metastasis were retrieved and stained for apolipoprotein B (apoB) immunohistochemistry (IHC) in our center.

Rhodium-catalyzed enantioselective C-H alkynylation of sulfoxides in diverse patterns: desymmetrization, kinetic resolution, and parallel kinetic resolution.

Rhodium-catalyzed enantioselective C-H alkynylation of achiral and racemic sulfoxides is disclosed with alkynyl bromide as the alkynylating reagent. A wide range of chiral sulfoxides have been constructed in good yield and excellent enantioselectivity (up to 99% ee, -factor up to > 500) desymmetrization, kinetic resolution, and parallel kinetic resolution under mild reaction conditions. The high enantioselectivity was rendered by the chiral cyclopentadienyl rhodium(iii) catalyst paired with a chiral carboxamide additive.

Neoadjuvant Immunotherapy Leads to Major Response and Low Recurrence in Localized Mismatch Repair-Deficient Colorectal Cancer.

Background: Our study aimed to evaluate the efficacy and feasibility of neoadjuvant anti-PD-1 treatment for localized mismatch repair-deficient (dMMR) colorectal cancer (CRC).

Patients And Methods: The study cohort included patients with localized dMMR CRC who received PD-1 inhibitors as neoadjuvant therapy from 3 medical centers in Southern China. Main eligibility criteria included age between 18 and 75 years, ECOG performance status of 0 or 1, and receipt of ≥2 doses of PD-1 inhibitors.

Inflammation promotes resistance to immune checkpoint inhibitors in high microsatellite instability colorectal cancer.

Inflammation is a common medical complication in colorectal cancer (CRC) patients, which plays significant roles in tumor progression and immunosuppression. However, the influence of inflammatory conditions on the tumor response to immune checkpoint inhibitors (ICI) is incompletely understood. Here we show that in a patient with high microsatellite instability (MSI-H) CRC and a local inflammatory condition, the primary tumor progresses but its liver metastasis regresses upon Pembrolizumab treatment.

CaMKII orchestrates endoplasmic reticulum stress and apoptosis in doxorubicin-induced cardiotoxicity by regulating the IRE1α/XBP1s pathway.

Doxorubicin (Dox), an anthracycline antibiotic with potent antitumor effects, has limited clinical applications due to cumulative cardiotoxicity. Ca /calmodulin-dependent protein kinase II (CaMKII) is implicated in the pathological progression of Dox-induced cardiotoxicity. This study examined the hypothesis that CaMKII exacerbates Dox-induced cardiotoxicity by promoting endoplasmic reticulum stress and apoptosis through regulation of the inositol-requiring enzyme 1α (IRE1α)/spliced X-box binding protein 1 (XBP1s) pathway.

DNA ploidy and stroma predicted the risk of recurrence in low-risk stage III colorectal cancer.

Background: For clinically low-risk stage III colorectal cancer, the decision on cycles of adjuvant chemotherapy after surgery is disputed. The present study investigates the use of additional biomarkers of ploidy and stroma-ratio(PS) to stratify patients with low-risk stage III colorectal cancer, providing a basis for individualized treatment in the future.

Methods: This study retrospectively enrolled 198 patients with clinical-low-risk stage III colorectal cancer (T1-3N1M0) and analyzed the DNA ploidy and stroma ratio of FFPE tumor tissues.

Anti-PD-1-based immunotherapy as curative-intent treatment in dMMR/MSI-H rectal cancer: A multicentre cohort study.

Background: In a portion of patients with DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) rectal cancer, clinical complete response (cCR) could be achieved after anti-programmed cell death protein 1 (anti-PD-1) immunotherapy. However, no data are available concerning the safety of omitting surgery and adopting immunotherapy as a curative-intent treatment for these patients.

Methods: We retrospectively collected a series of patients with dMMR/MSI-H rectal adenocarcinoma who had cCR after receiving anti-PD-1 immunotherapy and adopted immunotherapy as curative-intent treatment from six institutions.

Neoadjuvant Immune Checkpoint Inhibition Improves Organ Preservation in T4bM0 Colorectal Cancer With Mismatch Repair Deficiency: A Retrospective Observational Study.

Background: Colorectal cancer with mismatch repair deficiency is usually less aggressive and associated with a lower risk of distant metastasis. Immune checkpoint inhibition, rather than traditional chemoradiotherapy, has shown great advantages in treating such patients.

Objective: This study aimed to verify the hypothesis that locally very advanced (T4b) colorectal cancer without distant metastases might present with higher probability of mismatch repair deficiency and be more sensitive to neoadjuvant immune checkpoint inhibition.

Rhodium-Catalyzed Atroposelective C-H Arylation of (Hetero)Arenes Using Carbene Precursors as Arylating Reagents.

Rhodium(III)-catalyzed C-H activation-based arylation of sterically hindered (hetero)arenes has been realized using diazo compounds and triazoles as arylating reagents for atroposelective synthesis of two classes of biaryls. The coupling of 3-substituted indoles and -sulfonyltriazoles afforded indoles with a C(2)-C chiral axis, while the arylation of 1-naphthylthioether with -quinone diazide afforded chiral binaphthyls. These coupling systems proceeded under mild conditions via C-H activation and carbene insertion despite the steric hindrance of both the arenes and the carbene precursors.

miR-634 inhibits human vascular smooth muscle cell proliferation and migration in hypertension through Wnt4/β-catenin pathway.

MicroRNAs (miRNAs) have been regarded as modulators in vascular pathologies, including hypertension. Dysregulated proliferation and migration of VSMCs (vascular smooth muscle cells) contributes to vascular remodeling during hypertension. miR-634 was reported to be dysregulated in hypertensive patients.

Rhodium(iii)-catalyzed asymmetric [4+1] spiroannulations of O-pivaloyl oximes with α-diazo compounds.

Chiral Rh catalysts can catalyze the asymmetric [4+1] spiroannulation of O-pivaloyl oximes with α-diazo homophthalimides under redox-neutral and acid/base-neutral conditions, leading to formation of chiral spirocyclic imines as a result of C-H activation and N-O cleavage. The reaction proceeded with high efficiency and features broad substrate scope, mild reaction conditions, and high to excellent enantioselectivities.

Twofold C-H Activation-Based Enantio- and Diastereoselective C-H Arylation Using Diarylacetylenes as Rare Arylating Reagents.

C-H bond activation has been established as an attractive strategy to access axially chiral biaryls, and the most straightforward method is direct C-H arylation of arenes. However, the arylating source has been limited to several classes of reactive and bulky reagents. Reported herein is rhodium-catalyzed 1:2 coupling of diarylphosphinic amides and diarylacetylenes for enantio- and diastereoselective construction of biaryls with both central and axial chirality.

Dickkopf 1 impairs the tumor response to PD-1 blockade by inactivating CD8+ T cells in deficient mismatch repair colorectal cancer.

Background: Dickkopf 1 (DKK1) is associated with tumor progression. However, whether DKK1 influences the tumor response to programmed cell death protein 1 (PD-1) blockade in colorectal cancers (CRCs) with deficient mismatch repair (dMMR) or microsatellite instability (MSI) has never been clarified.

Methods: Tumor tissues from 80 patients with dMMR CRC were evaluated for DKK1 expression and immune status via immunohistochemistry.

Universal germline testing among patients with colorectal cancer: clinical actionability and optimised panel.

Purpose: Universal germline testing in patients with colorectal cancer (CRC) with a multigene panel can detect various hereditary cancer syndromes. This study was performed to understand how to choose a testing panel and whether the result would affect clinical management.

Methods: We prospectively enrolled 486 eligible patients with CRC, including all patients with CRC diagnosed under age 70 years and patients with CRC diagnosed over 70 years with hereditary risk features between November 2017 and January 2018.