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Background: The aim of the study is to evaluate clinical outcomes of patients with ovarian metastases from colorectal cancer (OM-CRC) treated with complete resection combined with chemotherapy and ...

Background Whether sarcopenia has an impact on immune-related adverse events (irAEs) in patients with malignant neoplasms receiving immune checkpoint inhibitors (ICIs) is not consistent. This study aimed to evaluate the impact of sarcopenia on all grades of irAEs. Methods PubMed, Embase, and Cochrane Library databases were systematically searched for related studies up to May 2021. Eligible studies were included according to the PICOS criteria. The risk of bias of the included studies was assessed according to the Newcastle-Ottawa Scale (NOS). The odds ratio (OR), corresponding to the 95% confidence interval (CI) of all grades of irAEs, was collected and analyzed, and a further subgroup analysis of serious adverse events was conducted. All analyses were conducted using the RevMan 5.4 software downloaded from the Cochrane website. The heterogeneity and sensitivity of the study were assessed. Results Of the 135 references identified, only 8 studies were analyzed, including 519 patients comprising 250 with sarcopenia and 269 without sarcopenia. No obvious bias was observed in the included studies. An increased incidence of irAEs was not observed in patients with sarcopenia at pre-immunotherapy compared to those without sarcopenia. The OR and corresponding 95% CI were 0.97 and 0.62–1.53, respectively (P=0.90), with low heterogeneity (P=0.17, I2 =32%). Further, severe adverse events were analyzed in three studies, and the results showed that sarcopenia was not related to irAEs (P=0.97). Conclusions Malignancies with sarcopenia at pre-immunotherapy may not increase the incidence of irAEs, and sarcopenia may not be a predictive factor for irAEs.

To investigate the association between polymorphisms in theA total of 81 patients with colon or rectal cancer were included in the study. The single nucleotide polymorphisms (SNPs) rs3127573, rs316019, and rs1869641 of theThe rs1869641 genotype was significantly associated with the occurrence of thrombocytopenia (p = 0.047), whereas the rs316019 genotype was significantly associated with severity of leucopenia and neutropenia (p = 0.004 and 0.001, respectively). The rs3127573 genotype was not associated with hematological toxicities arising during chemotherapy with oxaliplatin.It is shown here, for the first time, that the rs316019 gene variant of the

Objectives To analyze the clinicopathological parameters of advanced lung cancer patients who received Immune checkpoint inhibitors (ICIs) treatment to establish pre-treatment body mass index (BMI) as a predictor of immunotherapy response, patient survival, and immune-related adverse events (irAEs). Methods We retrospectively evaluated a cohort of 92 patients who received therapy with ICIs for advanced lung cancer at our hospital between January 2018 and January 2021. Patients were categorized into three groups based on BMI; an underweight group (BMI 2), a normal-weight group (18.5 kg/m2 ≤ BMI ≤ 24.9 kg/m2), and an overweight group (BMI ≥ 25 kg/m2). The correlations were observed between BMI and immunotherapy response, progression-free survival (PFS), and irAEs based on ICIs treatment. Results Pretreatment BMI levels were significantly associated with response to ICIs therapy in disease control rate (DCR) (p = 0.034) and PFS (p = 0.006) of patients with advanced lung cancer, and it was a non-significant trend towards objective response rate (ORR) (p = 0.086). Pretreatment BMI, gender, and PD-L1 expression level were independent prognostic factors for PFS in univariate and multivariate analyses: HR = 0.323, 95% CI: 0.141–0.737, p = 0.007, and HR = 0.277, 95% CI: 0.115–0.670, p = 0.004; gender: HR = 2.609, 95% CI: 1.198–5.683, p = 0.016; PD-L1: HR = 6.599, 95% CI: 1.555–27.996, p = 0.001). Higher BMI is a significant predictor for irAEs (p = 0 .016). Conclusion High pre-treatment BMI is associated with positive immunotherapy outcomes, while decreased BMI was associated with irAEs development.

Colon cancer, as one of the common malignant tumors, has the highest morbidity and mortality. We investigated the clinical significance and possible mechanism of the circular RNA circHIPK2 in the progression of colorectal cancer (CRC). Quantitative analysis of mRNAs, gene microarray hybridization, immunofluorescence, luciferase reporter assay, proliferation assay, EDU staining, subcellular location analysis and Western blotting. circHIPK2 expression was upregulated in patients with CRC compared with paracancerous tissues. In contrast, patients with high circHIPK2 expression had lower overall survival rate and disease-free survival rate than those with low circHIPK2 expression. circHIPK2 expression in normal intestinal epithelial cells was lower than that in CRC cell lines. circHIPK2 promoted CRC progression. miR-485-5p reduced CRC progression. miR-485-5p, as the target of circHIPK2 in CRC model, played a role in promoting CRC progression and expediting HSP90 ubiquitination. HSP90 ubiquitination by miR-485-5p can promote cell proliferation. circHIPK2 has potential clinical significance in CRC progression, which may serve as an exceptional candidate for further therapeutic exploration.

Xuan Wu,1– 3,* Jingxun Wu,4,* Gangling Tong,1– 3,* Boran Cheng,1– 3,* Minhua Chen,5,* Shaokang Yu,1– 3 Lirui He,6 Zhu Li,1– 3 Shubin Wang1– 3 1Department of Oncology, Peking University Shenzhen Hospital, Shenzhen 518036, People’s Republic of China; 2Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research, Shenzhen 518036, People’s Republic of China; 3Cancer Institute of Shenzhen-PKU-HKUST Medical Center, Shenzhen 518036, People’s Republic of China; 4Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen 361003, People’s Republic of China; 5Community Healthcare Center, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen 518033, People’s Republic of China; 6Department of Gastrointestinal Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shubin Wang Department of Medical OncologyPeking University Shenzhen Hospital, 1120 Lianhua Road, Shenzhen 518036, People’s Republic of ChinaTel +86 75683923333Fax +86 75683061340Email shubinwang2013@163.comPurpose: Dexamethasone combined with 5-hydroxytryptamine type 3 receptor antagonists (5-HT3 RA) dual regimen is the standard prophylaxis regimen for patients receiving moderately emetogenic chemotherapy (MEC). However, it has been found in real-world practice that chemotherapy-induced nausea and vomiting (CINV) remains poorly controlled among patients with gastrointestinal tumor, especially in those with high-risk factors for vomiting, such as female, young, and non-alcoholic individuals. Hence, we aimed to evaluate the efficacy of an olanzapine-containing triple regimen in this clinical setting.Patients and Methods: We retrospectively reviewed the clinical records of gastrointestinal tumor patients who received mFOLFOX6, XELOX, or FOLFIRI chemotherapy at two institutions. All patients included were female and less than 55 years old, with no history of drinking. The patients were divided into two groups for olanzapine-containing triple therapy (olanzapine, tropisetron, and dexamethasone) and non-olanzapine dual therapy (tropisetron and dexamethasone). The study outcomes were complete response (CR), complete control (CC), nausea control, and quality of life (QoL) by the functional living index-emesis (FLIE) questionnaire.Results: A total of 93 patients were included in the study (olanzapine: 40; control: 53). The CR rate in the olanzapine group was significantly higher than that in the control group in delayed and overall phase (75.0% vs 54.7%, p=0.044; 70.0% vs 47.2%; p=0.028). The CC rate in the overall phase was also better in the olanzapine group (62.5% vs 39.6%, p=0.029). The control of nausea in the overall phase showed a superior trend in the olanzapine group (p=0.059). The olanzapine group exhibited higher FLIE scores, which demonstrated better QoL. More patients in the olanzapine group exhibited somnolence and dizziness. Conversely, the incidence of insomnia and anorexia in the olanzapine group was lower.Conclusion: This retrospective study indicates that in gastrointestinal tumor patients with high-risk factors for CINV who were receiving MEC, olanzapine-containing triple antiemetic regimen exhibit better efficacy and QoL as compared to non-olanzapine dual regimen. Further randomized studies are required to confirm these results.Keywords: CINV, MEC, olanzapine, gastrointestinal tumor, high risk of emesis

Background The aim of this study was to evaluate the efficacy and safety of trastuzumab, combined with the FLOT regimen, in the perioperative treatment of resectable HER-2-positive advanced gastric cancer. Methods Overall, 45 patients were divided into two groups; 29 patients in the experimental group were treated with trastuzumab combined with FLOT and 16 patients in the control group were treated with FLOT alone. The primary endpoint was objective response rate (ORR), and the secondary endpoints were disease control rate (DCR), tumor regression grade (TRG), surgical margin, side effects, and overall survival. Results In the experimental and control groups, ORR was 72.4% and 43.8% (p=0.226), DCR was 89.7% and 87.5%, R0 resection rate was 96.5% and 93.7%, total/subtotal tumor regression grade was 17.2% and 6.3%, partial tumor regression grade was 27.6% and 18.7% (p=0.468), and 2-year survival rate was 78.1% and 73.9% (p=0.932), respectively. The common side effects were agranulocytosis and vomiting. There was no significant difference between the two groups. Conclusion Trastuzumab combined with FLOT has a good curative effect and safety profile in the perioperative treatment of patients with resectable HER-2-positive advanced gastric cancer. In addition, trastuzumab + FLOT had the same result as FLOT alone, as there was no significant benefit with the addition of T in the group studied.

Previous studies have shown that PD-L1-positive advanced gastric cancer (GC) patients could achieve clinical benefit after receiving immune checkpoint inhibitors (ICI) in initial or subsequent therapy. A number of prospective studies such as Keynote-158 have demonstrated that PD-L1-negative patients who tested as microsatellite instability-high (MSI-H) or tumor mutational burden-high (TMB-H) can benefit from ICIs. In the search for more biomarker for immunotherapy, some studies showed that patients with a specific characteristic to tumor microenvironment (TME) were associated with better prognosis. This study aimed to explore the association between the TME and immunotherapy in PD-L1 negative GC patients.This study was a retrospective cohort study. Twenty-six CPS PD-L1 negative stage IV advanced GC patients treated with chemoimmunotherapy in Shenzhen Hospital of Peking University were retrospectively enrolled according to the inclusion criteria. Their clinical characteristics were assessed and recorded by independent clinicians. Follow-up data was conducted through the Internet or visit. Respond to treatment was evaluated by RECIST 1.1. The primary outcome was progression-free survival (PFS). The level of tumor-infiltrating lymphocytes (TILs) was measured by multiplex immunofluorescence (mIF) among these patients. Cox proportional hazards analysis was performed to analyzed the correlation between PFS and clinical characteristics including TILs.Among 26 patients, 5 patients (19.2%) were on complete response (CR) and 9 patients (34.6%) were in partial response (PR), while 7 patients (26.9%) experienced stable disease (SD). Intratumoral CD8Intratumoral CD8

Emerging evidence suggests heterologous prime-boost COVID-19 vaccination as a superior strategy than homologous schedules. Animal experiments and clinical observations have shown enhanced antibody response against influenza variants after heterologous vaccination; however, whether the inoculation order of COVID-19 vaccines in a prime-boost schedule affects antibody response against SARS-CoV-2 variants is not clear.We conducted immunological analyses in a cohort of health care workers (n = 486) recently vaccinated by three types of inactivated COVID-19 vaccines under homologous or heterologous prime-boost schedules. Antibody response against ancestral SARS-CoV-2 (Wuhan-Hu-1) was assessed by total antibody measurements, surrogate virus neutralization tests, and pseudovirus neutralization assays (PNA). Furthermore, serum neutralization activity against SARS-CoV-2 variants of concern was also measured by PNA.We observed strongest serum neutralization activity against the widely circulating SARS-CoV-2 variant B.1.617.2 among recipients of heterologous BBIBP-CorV/CoronaVac and WIBP-CorV/CoronaVac. In contrast, recipients of CoronaVac/BBIBP-CorV and CoronaVac/WIBP-CorV showed significantly lower B.1.617.2 neutralization titers than recipients of reverse schedules. Laboratory tests revealed that neutralizing activity against common variants but not the ancestral SARS-CoV-2 was associated with the inoculation order of heterologous prime-boost vaccines. Multivariable regression analyses confirmed this association after adjusting for known confounders.Our data provide clinical evidence of inoculation order-dependent expansion of neutralizing breadth against SARS-CoV-2 in recipients of heterologous prime-boost vaccination and call for further studies into its underlying mechanism.National Key RD Program of China, National Development and Re-form Commission of China, National Natural Science Foundation of China, Shenzhen Science and Technology Innovation Commission, and US Department of Veterans Affairs.

Background Advanced gastric cancer (aGC) has a high global incidence and a high mortality rate and because of its high malignancy and heterogeneity, the existing methods for prognosis are limited, and a new treatment model is necessary. Circulating tumor cells (CTCs) could be considered as a "liquid biopsy" for tumor diagnosis and for monitoring treatment responses and predicting clinical outcome. Clinical studies support the efficacy of programmed cell death 1 (PD-1) immunotherapy in a subset of aGC. Methods Cell capture efficiency, as described by the CanPatrol CTC enrichment technique, was validated using artificial blood samples as well as blood samples from 32 aGC patients. Clinicopathologic data of patients were collected from the hospital information system. We used CanPatrol for CTC isolation, classification, and clinical analysis. Results A cell capture efficiency of >80% was achieved. Significant correlation was observed between CTC enumeration and clinicopathology parameters, including the Lauren classification (r=0.470, P=0.008), perineural invasion (r=0.393, P=0.029), TNM stage (r=0.740, P

OBJECTIVE: Recent studies suggest that abnormal snoRNA expression may play crucial role in tumor development and progression. In the study, we aim to explore the clinical significance and functional role of Small nucleolar RNA 78 (SNORD78) in breast cancer.PATIENTS AND METHODS: The expression of SNORD78 in 92 breast cancer and adjacent non tumor tissues was analyzed by quantitative real time polymerase chain reaction (qRT-PCR). The association between SNORD78 expression and clinicopathological factors was evaluated. The biological functions in vitro were examined by MTT cell proliferation, colony formation and transwell invasion assays. QRT-PCR and Western blot assays were used to analyze the mRNA and protein expression of WNT1, GSK3β and β-catenin.RESULTS: SNORD78 expression showed a significant increase in breast cancer tissues and cell lines. Higher SNORD78 expression positively was related to lymph node metastasis and TNM stage in patients. Furthermore, knockdown of SNORD78 inhibited the abilities of cell proliferation, colony formation, and cell invasion in MDA-MB-231 and SKBR-3 cells. Moreover, we demonstrated that knockdown of SNORD78 inhibited WNT/β-catenin signaling pathway in MDA-MB-231 and SKBR-3 cells via downregulating the relative protein expression of WNT1 and β-catenin and upregulating the GSK3β expression.CONCLUSION: Our results indicated that SNORD78 may be potential therapeutic target for breast cancer.

Summary Interferons (IFNs) are widely used in treating coronavirus disease 2019 (COVID-19) patients. However, a recent report of ACE2, the host factor mediating SARS-Cov-2 infection, identifying it as interferon-stimulated raised considerable safety concern. To examine the association between the use and timing of IFN-α2b and clinical outcomes, we analyzed in a retrospective multicenter cohort study of 446 COVID-19 patients in Hubei, China. Regression models estimated that early administration (≤5 days after admission) of IFN-α2b was associated with reduced in-hospital mortality in comparison with no admission of IFN-α2b, whereas late administration of IFN-α2b was associated with increased mortality. Among survivors, early IFN-α2b was not associated with hospital discharge or computed tomography (CT) scan improvement, whereas late IFN-α2b was associated with delayed recovery. Additionally, early IFN-α2b and umifenovir alone or together were associated with reduced mortality and accelerated recovery in comparison with treatment with lopinavir/ritonavir (LPV/r) alone. We concluded that administration of IFN-α2b during the early stage of COVID-19 could induce favorable clinical responses., Graphical Abstract, Highlights • 242 of 446 analyzed COVID-19 patients received IFN-α2b, a type I IFN • Early initiation of IFN therapy was associated with reduced mortality • IFN therapy was not associated with recovery time for COVID-19 • IFN-α2b was associated with better responses than were lopinavir/ritonavir, In a retrospective cohort study of 446 COVID-19 patients, Wang et al. determine that early administration of interferon-α2b was associated with reduced in-hospital mortality. In contrast, late interferon therapy increased mortality and delayed recovery, suggesting the timing of interferon therapy is crucial for favorable responses in COVID-19 patients.

e16029 Background: It was demonstrated that CPS PDL1 positive patients of advanced gastric cancer (GC) could benefit from specific immune checkpoint inhibitors (ICI) for first-line, and second-line or subsequent therapy. However, whether the application of ICI could lead to better clinical outcome in advanced GC patients who were negative for PDL1 remains further explore. Some studies showed that patients with specific tumor immune microenvironment (TME) are more sensitive to immunotherapy. Therefore, TME may be a potential positive predictor for PDL1 negative patients treated with immunotherapy. Methods: We retrospectively enrolled 26 advanced GC patients who were treated by chemoimmunotherapy in Shenzhen Hospital of Peking University and evaluated for clinical characteristics. Peritumoral and intratumoral Tumour-infiltrating lymphocytes (TIL) were detected by mIHC (multiplex immunofluorescence) among these patients. The correlation between PFS and clinical characteristics including TIL was analyzed by univariate survival analysis and multivariate Cox proportional hazards analysis. Results: In 26 patients, 5 patients (19.2%) experienced complete response (CR), 9 patients (34.6%) experienced partial response (PR), while 7 patients (26.9%) experienced stable disease (SD). Compared with non-responders, higher intratumoral infiltrating CD8+ T cells instead of other subtypes were detected in CPS PDL1 negative Patients who respond to chemoimmunotherapy. Further analysis revealed that CD8+ TIL was a predictive biomarker for PFS to chemo-immunotherapy in CPS PDL1 negative patients. Conclusions: For CPS PDL1 negative advanced GC patients, intratumoral CD8+ TIL may be a potential positive predictor for treatment of chemo-immunotherapy.

HOXC10 plays a critical role in many cellular processes, such as proliferation, migration, and invasion, but the function of HOXC10 in gastric carcinoma is not clear. In this study, we aimed to investigate the expression profile of HOXC10 and its role in gastric carcinoma cells and in vivo experiments. HOXC10 expression patterns were detected in clinical samples and gastric cancer cells lines by reverse transcriptase polymerase chain reaction assays, and then, we focused on its role in regulating cell proliferation, cell cycle, migration, and invasion after transfection of silencing and overexpression plasmids in vitro and in vivo. Finally, we confirmed the correlation between HOXC10 and nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), and epidermal growth factor receptor expression. We found that HOXC10 expression increased in clinical samples, especially in poorly differentiated (PD) gastric cancer cells. Silencing HOXC10 suppressed proliferation, migration, and invasion in vitro, and inhibited tumor growth and induced apoptosis in vivo. Overexpression of HOXC10 showed the opposite effect on PD gastric cancer cells. In addition, silencing HOXC10 inhibited the expression of interleukin-6, TNF-α, TGF-β, and epidermal growth factor, and overexpressing HOXC10 induced their expression both in vitro and in vivo. Luciferase reporter assays and chromatin immunoprecipitation indicated that HOXC10 may activate the NF-κB signaling pathway through regulation of P65 transcriptional activity by binding to the P65 promoter. HOXC10 may play an important role in PD gastric carcinoma cell proliferation, cell cycle, migration, invasion, and metastasis through upregulating proinflammatory cytokines via NF-κB pathway, suggesting HOXC10 may serve as a novel therapeutic target for PD gastric cancer.

At present, tumor diagnosis is performed using common procedures, which are slow, costly, and still presenting difficulties in diagnosing tumors at their early stage. Tumor therapeutic methods also mainly rely on large-scale equipment or non-intelligent treatment approaches. Thus, an early and accurate tumor diagnosis and personalized treatment may represent the best treatment option for a successful result, and the efforts in finding them are still in progress and mainly focusing on non-destructive, integrated, and multiple technologies. These objectives can be achieved with the development of advanced devices and smart technology that represent the topic of the current investigations. Therefore, this review summarizes the progress in tumor diagnosis and therapy and briefly explains the advantages and disadvantages of the described microdevices, finally proposing advanced micro smart devices as the future development trend for tumor diagnosis and therapy.

Colorectal cancer (CRC) remains one of the most common cancers worldwide. Increasing evidence indicates that long non-coding RNAs (lncRNAs) regulate diverse cellular processes, including cell growth, differentiation, apoptosis, and cancer progression. However, the function of lncRNAs in the progression of CRC remains largely unknown. Here, we reported that HOXA cluster antisense RNA2 (HOXA-AS2) was upregulated in CRC. Increased HOXA-AS2 expression in CRC was associated with larger tumor size and higher clinical stage. In vitro experiments revealed that HOXA-AS2 knockdown significantly inhibited CRC cell proliferation by causing G1 arrest and promoting apoptosis, whereas HOXA-AS2 overexpression promoted cell proliferation. Further functional assays indicated that HOXA-AS2 overexpression significantly promoted cell migration and invasion by regulating the epithelial-mesenchymal transition (EMT). In conclusion, our study identifies HOXA-AS2C as a potential biomarker in CRC.

T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/T-LBL) is commonly associated with Notch 1 mutations. There is limited data on the relationship between Notch l and NF-κB expression and clinical features in LBL. We evaluated the expression of Notch l and NF-κB in LBL using immunohistochemistry and analyzed their relationship with clinical characteristics, treatment results, and survival. From October 2000 to August 2008, 34 untreated patients with LBL were enrolled in the study. Median age was 11.8 years (range, 1 - 25 years). Twenty-five patients were diagnosed with T-LBL and 9 patients with B-LBL. Most patients received chemotherapy consisting of modified ALL-BFM- 90. Notch l showed high expression in 68% of T-LBL and low expression in 100% of B-LBL (p = 0.015). High expression of Notch l positively correlated with presence of a mediastinal mass but not with 5-year event free survival (EFS) in T-LBL. NF-κB showed high expression in 65% of all patients with LBL, with no difference between T- and B-LBL. NF-κB expression was higher in T-LBL patients with bulky disease and B symptom; it did not correlate with 5-year EFS in T-LBL. Expression of Notch 1 and NF-κB strongly correlated (p = 0.014) in T-LBL. Notch 1 is highly ex- pressed in T-LBL. NF-κB is highly expressed in all patients with LBL with no difference between T-LBL and B-LBL. Notch 1 expression was significantly associated with NF-κB expression in T-LBL. Notch l and NF-κB may play an important role in the development of T-LBL; further investigation is warranted.

11528 Background: Currently, response assessment of patients with non-small cell lung cancer (NSCLC) primarily relies on imaging scans, which do not reflect biological processes at the molecular level. We utilized circulating tumor DNA (ctDNA) coupled with capture-based ultra deep next generation sequencing to conduct dynamic monitoring of treatment response, thus evaluating the ability of ctDNA as a tumor clonal response biomarker. Methods: We performed capture-based sequencing on longitudinal plasma samples, including baseline and a minimum of 2 evaluation points, obtained from 88 patients with advanced NSCLC using a ctDNA panel, spanning 160KB of human genome and consisting of critical exons and introns from 168 genes. This real world study comprises a highly heterogeneous cohort with a mixture of prior treatment exposure. Results: At baseline, treatment-naïve patients often harbor solo driver mutation; in contrast, patients with prior treatments are more likely to harbor concurrent driver mutations. Patients who received molecular targeted therapy according to the baseline sequencing results have a longer progression-free survival (PFS) (p = 0.0001), demonstrating the value of ctDNA in directing treatment. During subsequent evaluations, we observed 74% concordance rate between molecular and radiographic responses. Furthermore, our data revealed that during follow-up, patients with at least one time of undetectable ctDNA are associated with a longer PFS (p = 5.52e-6), regardless the type of treatment commenced. Among 44 patients who had at least one time of undetectable ctDNA, 39 achieved partial response or stable disease as their best response. Collectively, this phenomenon reflects clonal response, thus demonstrating the biological nature underlying the clinical response assessed by imaging modalities. Conclusions: This real world study demonstrates that patients with at least one time of ctDNA clearance during subsequent evaluation are associated with a longer PFS. Our study warrants further investigations to explore the value of ctDNA clearance as a surrogate endpoint of efficacy and as a risk stratification factor.