Bevacizumab Combined with S-1 and Raltitrexed for Patients with Metastatic Colorectal Cancer Refractory to Standard Therapies: A Phase II Study.

LESSONS LEARNED: Bevacizumab combined with S-1 and raltitrexed demonstrated positive antitumor efficacy and acceptable toxicity. This combination might represent a treatment option for refractory metastatic colorectal cancer. BACKGROUND: In patients with metastatic colorectal cancer (mCRC) refractory to standard therapies, S-1 plus raltitrexed showed a good objective response rate (ORR) and significant survival benefit in our previous study. In the present study, we assessed the activity and safety of bevacizumab combined with S-1 and raltitrexed. METHODS: This investigator-initiated, open-label, single-arm, phase II trial was performed at West China Hospital in China. Patients with mCRC who had disease progression after fluoropyrimidine, irinotecan, and oxaliplatin and had at least one measurable lesion were eligible for this trial. Anti-epidermal growth factor receptor (EGFR) (for tumors with wild-type RAS) and anti-vascular endothelial growth factor (VEGF) therapy in the first or second line was allowed, but patients who had been treated with bevacizumab across two consecutive chemotherapy regimens were excluded. Patients received bevacizumab (7.5 mg/kg on day 1), oral S-1 (80-120 mg per day for 14 days), and raltitrexed (3 mg/m2 on day 1) every 3 weeks. The primary endpoint was ORR. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: From September 2015 to November 2019, 44 patients were enrolled. Tumor response evaluation was available in 44 patients at the time of the analysis. There were no complete responses; the ORR was 15.9%, and the disease control rate was 54.5%. Median PFS and OS were 110 days (95% confidence interval [CI], 65.0-155.0) and 367 days (95% CI, 310.4-423.6), respectively. The combination was well tolerated. CONCLUSION: Bevacizumab combined with S-1 and raltitrexed showed promising antitumor activity and safety in refractory mCRC.

Enhancement of the antitumor effect of HER2-directed CAR-T cells through blocking epithelial-mesenchymal transition in tumor cells.

The efficacy of chimeric antigen receptor T (CAR-T) cell therapy in solid tumors is far from satisfactory. In this study, we investigated the influence of epithelial-mesenchymal transition (EMT) on the antitumor effect of CAR-T cells and explored the potential efficacy of combining CAR-T cells with inhibitors targeting EMT. We successfully induced EMT in tumor cells with TGF-ß1, and the antitumor effect of HER2-directed CAR-T cells was significantly suppressed by EMT. Upregulation of PD-L1 was observed in tumor cells undergoing EMT, and change in PD-L1 expression during the EMT process was dependent on the MEK/ERK and PI3K/Akt pathways. Inhibition of the TGF-ß1 pathway could block the EMT process in tumor cells and restore their susceptibility to HER2-directed CAR-T cells in vitro. In addition, targeting the TGF-ß1 pathway significantly enhanced the antitumor effect of HER2-directed CAR-T cells in vivo. Our findings suggest that blocking EMT could potently enhance the antitumor effect of CAR-T cells, which provides a promising approach to improving the therapeutic efficacy of CAR-T cell therapy in solid tumors.

IL-18R-dependent and independent pathways account for IL-18-enhanced antitumor ability of CAR-T cells.

Interleukin-18 (IL-18) has been demonstrated to augment the antitumor capacity of chimeric antigen receptor-T cells (CAR-T) but the underlying mechanisms are largely unknown. Here we explored the effects and mechanisms of exogenous IL-18 on the antitumor response of CAR-T cells. IL-18 boosted the cytotoxicity of human epidermal growth factor receptor-2 (HER2)-specific CAR-T cells ex vivo and enhanced the antitumor efficacy of the CAR-T cells in immunodeficient mice, moreover, IL-18 improved the antitumor capacity of OVA-specific T cells in immunocompetent mice, indicating the universal enhancing function of IL-18 for adoptive cell therapy. To address the roles of IL-18 receptor (IL-18R) in the enhancing function, we evaluated the effects of IL-18R knockout (IL-18R-/-) condition in immunocompetent host and CAR-T cells on the IL-18-enhanced antitumor activities. Interestingly, IL-18 persisted to improve the antitumor ability of IL-18R intact CAR-T cells in IL-18R-/- mice. For IL-18R-/- CAR-T cells, however, IL-18 still holds the enhancing ability to boost the antitumor efficacy in IL-18R-/- mice, albeit the ex vivo tumor-killing ability was lower than that of IL-18R intact CAR-T cells, indicating that IL-18R-independent pathway is involved in the enhancement. Furthermore, tagged IL-18 binded to the membrane of IL-18R-/- splenic and lymph node cells and IL-18R intact and IL-18R-/- CAR-T cells showed distinct transcriptomic profiles when stimulated by IL-18. These data demonstrate that IL-18R-independent pathways contribute to functions of IL-18.

S-1 plus Raltitrexed for Refractory Metastatic Colorectal Cancer: A Phase II Trial.

LESSONS LEARNED: The upregulation of dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) are important mechanisms of resistance to 5-fluorouracil (5-FU) in metastatic colorectal cancer (mCRC) after long exposure to 5-FU.S-1 (containing a DPD inhibitor) combined with raltitrexed (a TS inhibitor) showed a moderate effect, which needs further study as a third- or later-line therapy in mCRC. BACKGROUND: 5-fluorouracil (5-FU) is a fundamental drug in the treatment of metastatic colorectal cancer (mCRC). Patients with mCRC are often exposed to 5-FU and/or its analogues for a long time because of its central role in treatment regimens. The upregulation of dihydropyrimidine dehydrogenase (DPD) and/or thymidylate synthase (TS) are important mechanisms of resistance of 5-FU. To evaluate the efficacy and safety of S-1 (containing a DPD inhibitor) and raltitrexed (a TS inhibitor) for refractory mCRC, a one-center, single-arm, prospective phase II trial was conducted. METHODS: Patients who had mCRC that had progressed after treatment with fluoropyrimidine, irinotecan, and oxaliplatin and who had at least one measurable lesion were eligible for this trial. Patients received oral S-1 (80-120 mg for 14 days every 3 weeks) plus an intravenous infusion of raltitrexed (3 mg/m2 on day 1 every 3 weeks). The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: In total, 46 patients were enrolled. Three patients did not complete the first assessment because of adverse events and unwillingness, leaving tumor response evaluation available in 43 patients. Of 43 evaluable patients, the ORR was 13.9% and disease control rate was 58.1%. In the intention-to-treat population (n = 46), the ORR was 13.0% and disease control rate was 54.3%. Median PFS and median OS were 107 days (95% confidence interval [CI], 96.3-117.7) and 373 days (95% CI, 226.2-519.8), respectively. Most of the adverse effects were mild to moderate. CONCLUSION: S-1 combined with raltitrexed for refractory mCRC showed moderate effect, and it is worthy of further study as third- or later-line therapy in mCRC.

Improved therapeutic potential of MSCs by genetic modification.

Mesenchymal stem cells (MSCs), well-studied adult stem cells in various tissues, possess multi-lineage differentiation potential and anti-inflammatory properties. MSCs have been approved to regenerate lineage-specific cells to replace injured cells in tissues. MSCs are approved to treat inflammatory diseases. With the discovery of genes important for the repair of damaged tissues, MSCs genetically modified by such genes hold improved therapeutic potential. In this review, we summarised the uses of genetically modified MSCs to treat different diseases, including bone diseases, cardiovascular diseases, autoimmune diseases, central nervous system disorders, and cancer. To better understand the exact role of genetically modified MSCs, key mechanisms determining, which genes are selected to be used for modifying MSCs and improvements in post-genetic modification are discussed. Therapeutic benefits enhanced by genetic modifications are to be documented by further clinical studies.

Y-QA31, a novel dopamine D3 receptor antagonist, exhibits antipsychotic-like properties in preclinical animal models of schizophrenia.

AIM: To investigate the potential effects of Y-QA31, a novel dopamine D3 receptor antagonist, as an antipsychotic drug. METHODS: A panel of radioligand-receptor binding assays was performed to identify the affinities of Y-QA31 for different G protein-coupled receptors. [(35)S]GTPγS-binding assays and Ca(2+) imaging were used to assess its intrinsic activities. The antipsychotic profile of Y-QA31 was characterized in mouse models for the positive symptoms and cognitive deficits of schizophrenia and extrapyramidal side effects with haloperidol and clozapine as positive controls. RESULTS: In vitro, Y-QA31 is a dopamine D3 receptor antagonist that is 186-fold more potent at the D3 receptor than at the D2 receptor. Y-QA31 also exhibits 5-HT1A receptor partial agonist and α1A adrenoceptor antagonist activities with medium affinity, whereas it exhibits very little affinity for other receptors (100-fold lower than for the D3 receptor). In vivo, Y-QA31 (10-40 mg/kg, po) significantly inhibited MK-801-induced hyperlocomotion and methamphetamine-induced prepulse inhibition disruption in a dose-dependent manner. Y-QA31 also inhibited the avoidance response and methamphetamine-induced hyperlocomotion with potency lower than haloperidol. Y-QA31 was effective in alleviating the MK-801-induced disruption of novel object recognition at a low dose (1 mg/kg, po). Moreover, Y-QA31 itself did not affect spontaneous locomotion or induce cataleptic response until its dose reached 120 mg/kg. CONCLUSION: Y-QA31 is a selective D3R antagonist that exhibits antipsychotic effects in some animal models with positive symptoms and cognitive disorder and less extrapyramidal side effects.

[Chemical Constituents of Cynanchum auriculatum].

OBJECTIVE: To study the chemical constituents of Cynanchum auriculatum. METHODS: Nine compounds were isolated by silica gel, RP-18 column chromatography and Sephadex LH20. RESULTS: Nine compounds were isolated from the ethanol extract of Cynanchum auriculatum. Their structures were determined as sarcosin-3-O-ß-cymaropyranoside (1), cynotophylloside B (2), clemaphenol A (3), deacetylmetaplexigenin (4), methyl-2,6-dideoxy-3-O-methyl-ß-D-arabino-hexopyranosyl- (1 --> 4) -6-deoxy-3-O-methyl-α-L-ribo-hexopyranoside (5), trans-p-hydroxy cinnamic methyl ester (6), cyclo(D-Pro-D-Leu) (7), 3α-hydroxy-5α ,6α-epoxy-7-megastigmen9-one (8) and ferulic acid methyl ester (9) on the basis of spectral analysis. CONCLUSION: Compounds 3, 5 and 6 - 9 are isolated from Cynanchum auriculatum for the first time.

A case of penile squamous cell carcinoma treated with a combination of antiepidermal growth factor receptor antibody and chemotherapy.

Our previous study showed that the features of epidermal growth factor receptor (EGFR)-RAS signaling in penile squamous cell carcinoma (SCC) suggested potential benefits of anti-EGFR monoclonal antibodies (mAbs) for penile SCC. Here, we report, for the first time, a combination of nimotuzumab (an EGFR mAb) with chemotherapy that resulted in a partial response in a 44-year-old patient with penile SCC, who developed bilateral inguinal node metastasis after primary partial penile amputation. The literature of case reports of anti-EGFR mAbs in penile SCC was also reviewed.

Dynamic ctDNA-based analysis of drug-resistant gene alterations at RAS/BRAF wild-type metastatic colorectal cancer patients after cetuximab plus chemotherapy as the first-line treatment.

BACKGROUND: The purpose of this study was to explore the dynamic changes of genomic mutations and their correlations with the efficacy in metastatic colorectal cancer (mCRC) patients treated with cetuximab plus mFOLFOX as the first-line treatment. METHODS: We included mCRC patients from January 2018 to October 2020 as a studied cohort which were treated with cetuximab plus mFOLFOX as first line therapy. Blood samples were collected for circulating tumor DNA (ctDNA) test at three timepoints: before the first-line therapy(baseline), at the time of first-line progression and at the time of second-line progression. Progression-free survival was considered as the primary endpoint while objective response rate and overall survival were determined as the secondary endpoints. RESULTS: Totally 39 patients received first-line treatment, of which 25 patients entered the second-line treatment, while 10 patients entered the third-line treatment. The median follow-up time was 16.4 months (95 %CI, 14.8-19.3). Along the treatment from first-line progress disease (PD) to second-line PD, proportions of TP53 (12/18, 67 %), APC (10/18, 56 %), FBXW7 (3/18, 17 %), and AMER1 (2/18, 11 %) were gradually increased according to results of single nucleotide variation (SNV). CONCLUSIONS: Resistant gene mutations caused by anti-EGFR drugs in RAS/BRAF wild-type mCRC patients can be observed by dynamic ctDNA analysis. TP53 and AMER1 mutations, tumor mutational burden (TMB) levels, and TP53/AMER1 co-mutation may predict the efficacy of the first-line cetuximab-contained treatment. Situations of genetic mutations were differentiated from first-line PD to second-line PD, which indicated that mutation detection may contribute to predict prognosis of mCRC patients.

Clinical characteristics of patients with solitary pulmonary mass after radical treatment for primary cancers: pulmonary metastasis or second primary lung cancer?

We identified clinical characteristics of 30 pulmonary metastasis (PM) patients and 29 second primary lung cancer (SPLC) patients with feature of solitary pulmonary mass (SPM) after radical treatment of prior cancers. 6.7% and 44.8% patients presented with centrally located SPM and the median event-free durations were 33 and 72 months in PM and SPLC groups, respectively. PM was more likely to be found in prior cancers with stage III. In conclusion, the location of SPM, the event-free duration and the prior tumor staging were important features for differentiating SPLC from PM among patients with SPM after prior cancers.

[Expression of thymidylate synthase and dihydropyrimidine dehydrogenase in penile cancer].

OBJECTIVE: To investigate the expression of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) in penile cancer. METHODS: A total of 96 patients with penile cancer were included, the expression of TS and DPD in tumor tissues were examined by immunohistochemistry method, the relationship of TS and DPD expressions with the clinical characters were also analyzed. RESULTS: The expression of TS and DPD in penile cancer tissue were 41. 67% (40/96) and 33. 33% (32/96) respectively. There was a positive correlation between TS and DPD expression (Pearson C= 0. 362, P<0. 01). DPD was found to be more expressed in non-smoking patients (P = 0. 040). CONCLUSION: TS and DPD were moderately expressed in penile cancer and their expressions were positively correlated. This could be helpful for the application of fluorouracil in chemotherapy for the patients with penile cancer.

Case report: Remarkable response to sintilimab, lenvatinib, and nab-paclitaxel in postoperative metastatic chemotherapy-resistant combined hepatocellular-cholangiocarcinoma.

Background: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a highly aggressive malignancy with a poor prognosis. However, there are no consensus treatment guidelines, and decisions are usually extrapolated from intrahepatic cholangiocarcinoma (ICC) or hepatocellular carcinoma (HCC). Given that cHCC-CCA owns the unequivocal presence of both hepatocytic and cholangiocytic differentiation, a combination regimen of anti-PD1 antibody, multikinase inhibitor, and chemotherapy targeting against both components might be an optimal choice. Case presentation: We present the case of a patient with postoperative metastatic chemotherapy-resistant cHCC-CCA who exhibited a durable response and reasonable tolerability to a combination therapy consisting of the anti-PD1 antibody sintilimab, multikinase inhibitor lenvatinib, and nab-paclitaxel, despite having a low tumor mutational burden (TMB-L), microsatellite stability (MSS), and negative programmed cell death 1 ligand 1 (PD-L1). Conclusion: The combination regimen of immune checkpoint inhibitor sintilimab, multikinase inhibitor lenvatinib, and chemotherapy with nab-paclitaxel, which targets both the HCC and ICC components, may represent a promising treatment option for patients with cHCC-CCA. Further research is warranted to validate these findings in larger patient cohorts.

Development of a multiplex qRT-PCR assay for the detection of porcine epidemic diarrhea virus, porcine transmissible gastroenteritis virus and porcine Deltacoronavirus.

Currently, porcine coronaviruses are prevalent in pigs, and due to the outbreak of COVID-19, porcine coronaviruses have become a research hotspot. porcine epidemic diarrhea virus (PEDV), Transmissible Gastroenteritis Virus (TGEV), and Porcine Deltacoronavirus (PDCoV) mentioned in this study mainly cause diarrhea in pigs. These viruses cause significant economic losses and pose a potential public health threat. In this study, specific primers and probes were designed according to the M gene of PEDV, the S gene of TGEV, and the M gene of PDCoV, respectively, and TaqMan probe-based multiplex real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was developed for the simultaneous detection of PEDV, TGEV, and PDCoV. This method has high sensitivity and specificity, and the detection limit of each virus can reach 2.95 × 100 copies/µl. An assay of 160 clinical samples from pigs with diarrhea showed that the positive rates of PEDV, TGEV, and PDCoV were 38.13, 1.88, and 5.00%; the coinfection rates of PEDV+TGEV, PEDV+PDCoV, TGEV+PDCoV, PEDV+TGEV+PDCoV were 1.25, 1.25, 0, 0.63%, respectively. The positive coincidence rates of the multiplex qRT-PCR and single-reaction qRT-PCR were 100%. This method is of great significance for clinical monitoring of the porcine enteric diarrhea virus and helps reduce the loss of the breeding industry and control the spread of the disease.

Role of intestinal flora in primary sclerosing cholangitis and its potential therapeutic value.

Primary sclerosing cholangitis (PSC) is an autoimmune disease characterized by chronic cholestasis, a persistent inflammation of the bile ducts that leads to sclerotic occlusion and cholestasis. Gut microbes, consisting of microorganisms colonized in the human gut, play an important role in nutrient intake, metabolic homeostasis, immune regulation, and immune regulation; however, their presence might aid PSC development. Studies have found that gut-liver axis interactions also play an important role in the pathogenesis of PSC. Patients with PSC have considerably reduced intestinal flora diversity and increased abundance of potentially pathogenic bacteria. Dysbiosis of the intestinal flora leads to increased intestinal permeability, homing of intestinal lymphocytes, entry of bacteria and their associated metabolites, such as bile acids, into the liver, stimulation of hepatic immune activation, and promotion of PSC. Currently, PSC effective treatment is lacking. However, a number of studies have recently investigated the targeted modulation of gut microbes for the treatment of various liver diseases (alcoholic liver disease, metabolic fatty liver, cirrhosis, and autoimmune liver disease). In addition, antibiotics, fecal microbiota transplantation, and probiotics have been reported as successful PSC therapies as well as for the treatment of gut dysbiosis, suggesting their effectiveness for PSC treatment. Therefore, this review briefly summarizes the role of intestinal flora in PSC with the aim of providing new insights into PSC treatment.

How do intestinal probiotics restore the intestinal barrier?

The intestinal barrier is a structure that prevents harmful substances, such as bacteria and endotoxins, from penetrating the intestinal wall and entering human tissues, organs, and microcirculation. It can separate colonizing microbes from systemic tissues and prevent the invasion of pathogenic bacteria. Pathological conditions such as shock, trauma, stress, and inflammation damage the intestinal barrier to varying degrees, aggravating the primary disease. Intestinal probiotics are a type of active microorganisms beneficial to the health of the host and an essential element of human health. Reportedly, intestinal probiotics can affect the renewal of intestinal epithelial cells, and also make cell connections closer, increase the production of tight junction proteins and mucins, promote the development of the immune system, regulate the release of intestinal antimicrobial peptides, compete with pathogenic bacteria for nutrients and living space, and interact with the host and intestinal commensal flora to restore the intestinal barrier. In this review, we provide a comprehensive overview of how intestinal probiotics restore the intestinal barrier to provide new ideas for treating intestinal injury-related diseases.

The gut microbiota-bile acid axis: A potential therapeutic target for liver fibrosis.

Liver fibrosis involves the proliferation and deposition of extracellular matrix on liver tissues owing to various etiologies (including viral, alcohol, immune, and metabolic factors), ultimately leading to structural and functional abnormalities in the liver. If not effectively treated, liver fibrosis, a pivotal stage in the path to chronic liver disease, can progress to cirrhosis and eventually liver cancer; unfortunately, no specific clinical treatment for liver fibrosis has been established to date. In liver fibrosis cases, both the gut microbiota and bile acid metabolism are disrupted. As metabolites of the gut microbiota, bile acids have been linked to the progression of liver fibrosis via various pathways, thus implying that the gut microbiota-bile acid axis might play a critical role in the progression of liver fibrosis and could be a target for its reversal. Therefore, in this review, we examined the involvement of the gut microbiota-bile acid axis in liver fibrosis progression to the end of discovering new targets for the prevention, diagnosis, and therapy of chronic liver diseases, including liver fibrosis.

Clinicopathologic features, treatment, survival, and prognostic factors of combined hepatocellular and cholangiocarcinoma: A nomogram development based on SEER database and validation in multicenter study.

PURPOSE: The aim of the study was to comprehensively understand the combined hepatocellular and cholangiocarcinoma (CHC) and develop a nomogram for prognostic prediction of CHC. METHODS: Data were collected from the Surveillance, Epidemiology and End Results (SEER) database (year 2004-2014). Propensity-score matching (PSM) was used to match the demographic characteristic of the CHC versus hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). A nomogram model was established to predict the prognosis in terms of cancer specific survival (CSS). The established nomogram was externally validated by a multicenter cohort. RESULTS: A total of 71,756 patients enrolled in our study including 62,877 HCC patients, 566 CHC patients, and 8303 ICC patients. The CHC, HCC, and ICC are not exactly similar in clinical characteristic. After PSM, the CSS of CHC was better than HCC but comparable to ICC. Tumor size, M stage, surgery, chemotherapy, and surgery were independently prognostic factors of CHC and were included in the establishment of novel nomogram. The c-index of the novel nomogram in SEER training set and multicenter validation was 0.779 and 0.780, respectively, which indicated that the model was with better discrimination power. In addition, decision curve analyses proved the favorable potential clinical effect of the predictive model. Lastly, a risk classification based on nomogram also verified the reliability of the model. CONCLUSION: CHC had better survival than HCC but was comparable to ICC. The nomogram was established based on tumor size, M stage, chemotherapy, surgery, and radiotherapy and well validated by external multicenter cohort.

Antiemetic activity of megestrol acetate in patients receiving chemotherapy.

PURPOSE: Several trials had independently noted that patients receiving megestrol acetate had less nausea and vomiting, but this antiemetic activity of megestrol acetate has not been reported separately in the literature. Our objective was to evaluate the antiemetic ability of megestrol acetate in patients receiving chemotherapy. PATIENTS AND METHODS: Patients receiving chemotherapy were randomly assigned to receive either megestrol acetate 320 mg PO or placebo before the first day of chemotherapy, followed on days 1-4 by megestrol acetate 320 mg PO combined with granisetron 3 mg IV and metoclopramide 20 mg IM or only granisetron 3 mg IV combined with metoclopramide 20 mg IM in a crossover manner during two consecutive cycles. Rates of complete protection against both vomiting and moderate-to-severe nausea was the primary end point. RESULTS: One hundred patients were enrolled in the study. The antiemetic regimen containing megestrol acetate was superior in providing complete protection from nausea and vomiting (45% megestrol acetate regimen vs.17% no megestrol acetate regimen). Complete response of acute phase in both antiemetic regimens was different (85% megestrol acetate regimen vs. 72% no megestrol acetate regimen). Complete response of delayed emesis was also different (49% megestrol acetate regimen vs. 18% no megestrol acetate regimen). Adverse events were mostly mild to moderate. There were no serious drug-related adverse events between the two antiemetic regimens. CONCLUSION: Megestrol acetate was shown to be an effective antiemetic agent. Megestrol acetate might be a new antiemetic option for chemotherapy.

First-line therapy of bevacizumab plus chemotherapy versus cetuximab plus chemotherapy for metastatic colorectal cancer patients with mucinous adenocarcinoma or mucinous component.

BACKGROUND: To compare the efficacy of first-line bevacizumab plus chemotherapy with cetuximab plus chemotherapy based on the stratification of metastatic colorectal cancer (mCRC) patients with mucinous adenocarcinoma (MA) or mucinous component (MC). METHODS: A retrospective study involving all mCRC patients receiving first-line bevacizumab-based or cetuximab-based chemotherapy at our hospital from September 2013 to January 2020 was conducted. Overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were compared between the cetuximab-chemotherapy group and the bevacizumab-chemotherapy group on the basis of the conventional pathological classification of MA or MC. RESULTS: A total of 620 patients with mCRC were included in our study, consisting of 141 (22.7%) patients with MA/MC and 479 (77.3%) patients with non-mucinous adenocarcinoma (NMA). In the MA/MC cohort, patients who were treated with bevacizumab-based chemotherapy were associated with significantly better OS than those treated with cetuximab-base chemotherapy (30.0 vs. 26.3 months, p = 0.002), irrespective of tumor sites. The efficacy of bevacizumab-based chemotherapy was higher in nearly all subgroups as shown in the subgroup analysis. In the NMA cohort, median OS was better in the cetuximab plus chemotherapy group than that in the bevacizumab plus chemotherapy group (32.2 vs. 27.0 months, p = 0.005) for left-side mCRC patients, whereas OS was significantly longer in the bevacizumab plus chemotherapy group for right-side mCRC patients (26.0 vs. 20.9 months, p = 0.013). CONCLUSION: Conventional pathological classification (e.g. MA/MC) should be considered when tailoring the individualized optimal treatment for mCRC. Bevacizumab plus chemotherapy as first-line therapy may be the optimal option for patients with MA/MC.

Molding a silver nanoparticle template on polydimethylsiloxane to efficiently capture mammalian cells.

Herein, a functional template made up of in situ synthesized silver nanoparticles (AgNPs) is prepared on polydimethylsiloxane (PDMS) for the spatial control of cell capture, where the residual Si-H groups in the PDMS matrix are used as reductants to reduce AgNO(3) for forming AgNPs. In virtue of microfluidic system, a one-dimensional array pattern of AgNPs is obtained easily. Further combining with plasma treatment, a two-dimensional array pattern of AgNPs could be achieved. The obtained PDMS-AgNPs composite is characterized in detail. The PDMS-AgNPs composite shows good antibacterial property in E. coli adhesion tests. The patterns possess hifi and high resolution (ca. 8 microm). Cell patterns with high efficiency and spatial selectivity are further formed with the aid of H-Arg-Gly-Asp-Cys-OH (RGDC) tetrapeptide which is grafted on the AgNPs template. Cells immobilized on the template show a good ability for adhesion, spreading, migration, and growth.