An Efficient Technique for One-Dimensional Fractional Diffusion EquationModel for Cancer Tumor

This study intends to examine the analytical solutions to the resulting one-dimensional differential equation of acancer tumor model in the frame of time-fractional order with the Caputo-fractional operator employing a highlyefficient methodology called the q-homotopy analysis transform method.So,the preferred approach effectivelyfound the analytic series solution of the proposed model.The procured outcomes of the present frameworkdemonstrated that this method is authentic for obtaining solutions to a time-fractional-order cancer model.Theresults achieved graphically specify that the concerned paradigm is dependent on arbitrary order and parametersand also disclose the competence of the proposed algorithm.

The Continuous Relative Deficiency of Intracellular Potassium Is a Core Mechanism for the Occurrence and Metastasis of Tumor Cancer Cells

The core mechanism for occurrence of tumor cancer cells is related to the continuous relative deficiency of potassium ions in the cells of organs and tissues, which results in embryonic like proliferation and differentiation in the affected cells. The purpose of the metastasis of cancer cells is to obtain and utilize the potassium resources in other organs in body. However, if the overall potassium storage in body is obviously insufficient, the metastatic cancer cells still fail to achieve the purpose of obtaining enough potassium and turn into normal cells, further proliferation and differentiation of cancer cells will continue, and finally will lead to functional decline in the organs and tissues affected or death. Therefore, the key means to prevent and treat tumors and cancers is to ensure the normal and balanced potassium ions in cells in various organs and tissues, so as to avoid the formation of tumors and cancer cells caused by obvious deficiency of potassium ions.

Health-related quality of life evaluated by tumor node metastasis staging system in patients with hepatocellular carcinoma

AIM: To investigate and evaluate the change in healthrelated quality of life (HRQoL) by tumor node metastasis (TNM) staging system in patients with hepatocellular carcinoma (HCC). METHODS: A total of 140 patients diagnosed with HCC between June 2008 and April 2009 in our department were enrolled to this study. One hundred and thirty-five (96.5%) patients had liver cirrhosis secondary to hepatitis B virus (HBV) infection, 73 (54.07%) of them being HBV DNA positive; the other etiologies of liver cirrhosis were alcoholic liver disease (1.4%), hepatitis C (1.4%) or cryptogenic (0.7%). All subjects were fully aware of their diagnosis and provided informed consent. HRQoL was assessed before treatment using the functional assessment of cancer therapy-hepatobiliary (FACT-Hep) questionnaire. Descriptive statistics were used to evaluate demographics and disease-specific characteristics of the patients. One-way analysis of variance and independent samples t tests were used to compare the overall FACT-Hep scores and clinically distinct TNM stages. Scores for all FACT-Hep items were analyzed by frequency analyses. The mean scores obtained from the FACT-Hep in different Child-Pugh classes were also evaluated. RESULTS: The mean FACT-Hep scores were reduced significantly from TNM StageⅠto Stage Ⅱ, Stage ⅢA, Stage ⅢB group (687 ± 39.69 vs 547 ± 42.57 vs 387 ± 51.24 vs 177 ± 71.44, P = 0.001). Regarding the physical and emotional well-being subscales, scores decreased gradually from Stage Ⅰ to Stage ⅢB (P = 0.002 vs Stage Ⅰ; P = 0.032 vs Stage Ⅱ; P = 0.033 vs Stage ⅢA). Mean FACT-Hep scores varied by Child-Pugh class, especially in the subscales of physical well-being, functional well-being and the hepatobiliary cancer (P = 0.001 vs Stage I; P = 0.036 vs Stage Ⅱ; P = 0.032 vs Stage ⅢA). For the social and family well-being subscale, only Stage ⅢB scores were significantly lower as compared with Stage Ⅰ scores (P = 0.035). For the subscales of functional well-being and hepatobiliary cancer, there were significant differences for Stages ⅡΙ, ⅢA and ⅢB (P = 0.002vs StageⅠ). CONCLUSION: HRQoL of patients with HCC worsens gradually with progression of TNM stages. The most impaired subscales of HRQoL, as measured by FACT-Hep, were physical and emotional well-being.

Effect of Qinggan Huayu granule on H22 liver ascitic tumor mice

Objective:To evaluate the therapeutic effect of Qinggan Huayu granule on mice with H22 liver cancer ascites tumor.Methods:A H22 liver cancer ascites mouse model was established by intraperitoneally injecting H22 liver cancer cells.Mice were randomly divided into the model group,the Ganfule group(1.35 g/kg),the fluorouracil group(50 mg/kg i.p),the Qinggan Huayu granule groups at low(0.67 g/kg),medium(1.34 g/kg),and high(2.68 g/kg)doses.Then the mice were administered continuously for 10 days and body weight and abdominal circumference were monitored every 3 days.On day 11,eight rats in each group were randomly selected for dissection to detect the amount of peritoneal water,peritoneal permeability and histopathological changes.The remaining mice were observed for survival.In addition,the vascular endothelial growth factor A(VEGFA)and vascular endothelial growth factor receptor 2(VEGFR2)were determined by Western blotting.Results:Compared with the model group,the weight growth of mice in the fluorouracil group and the medium-dose and high-dose Qinggan Huayu granule groups was slower(P<0.05).Moreover,the abdominal circumference of mice in each treatment group was increased slowly.There were significant differences in abdominal circumference between the fluorouracil group,the medium-dose group and the control group from day 6(P<0.05)while the abdominal circumference of the high dose group was significantly smaller than that of the control group from day 12(P<0.05).Moreover,compared with the model group,the amount of ascites in the medium-and high-dose Qinggan Huayu granule groups was decreased significantly(P<0.05).The optical density value of ascites supernatant in medium-and high-dose Qinggan Huayu granule group and the fluorouracil group decreased significantly(P<0.05)and the survival period of the medium-dose Qinggan Huayu granule group and the fluorouracil group was prolonged prominently(P<0.05).There was no significant difference in the low-dose Qinggan Huayu granule group and the Ganfule group.Peritoneal histopathological assay showed more complete peritoneal structure,less edema and less angiogenesis of the peritoneum in the fluorouracil group and the medium-and high-dose Qinggan Huayu granule group,which was better than that of the Ganfule group and the low-dose group.Compared with the model group,the expressions of VEGFA and VEGFR2 in the medium-dose Qinggan Huayu granule group decreased significantly(P<0.05,P<0.01).Conclusion:Qinggan Huayu granule can inhibit ascites production in the mice model with H22 liver cancer ascites tumor,prolong the survival of mice,and reduce peritoneal permeability and suppress the increase of peritoneal neovascularization.The mechanism may be related to the inhibition of VEGF/VEGFR pathway.

CYTOTOXICITY OF INDIRECT IMMUNOTOXIN MEDIATED BY ANTI-GASTRIC CANCER MONOCLONAL ANTIBODIES ON TUMOR CELLS

In the present study, an indirect assay was employed to investigate 5 anti-gastric cancer monoclonal antibodies for their cytotoxic potential as ricin A chain-containing immunotoxins. The tumor cell, were treated with dilutions of tested antibody followed by ricin A chain coupled to goat anti-mouse immunoglobulin. The cytotoxic effect was determined with tetrazolium colorimetric assay. The results showed that among the 5 antibodies chosen, MGb2 and MG7 could be well used for preparation of effective A chain immunotoxins.

Implication of serum levels of interleukin-18 and nitric oxide in tumor growth and metastasis of non-small cell lung cancer

To study the effect of IL-18 and nitric oxide(NO) on the growth and metastasis of non-small cell lung cancer (NSCLC).Methods Serum IL-18 and nitrate and nitrite levels in 82 patients with NSCLC and 20 healthy control subjects were measured by using ELISA and Griess.Results The levels of serum IL-18 were (334.2±31.0)ng/L in NSCLC patients and (151.3±22.0)ng/L in control subjects,respectively.The levels of nitrate and nitrite were (237.1±21.0)μmol/L in NSCLC patients and (44.2±15.0)μmol/L in control subjects.The levels of serum IL-18 and nitrate and nitrite were not related with age,gender,histological types in patients with NSCLC.The levels of serum IL-18 was closely associated with TNM stage,lymph node metastasis and distal metastasis,but not with its degree and organ types of metastasis.There was a negative correlation between the levels of serum IL-18 and nitrate and nitrite.Conclusion Serum IL-18 and nitrate and nitrite levels may be useful to evaluate the prognosis of the patients with NSCLC.16 refs,2 tabs.

Changing paradigm of cancer therapy：precision medicine by next-generation sequencing

Precision medicine aims to identify the right drug, for the right patient, at the right dose, at the right time, which is particularly important in cancer therapy. Problems such as the variability of treatment response and resistance to medication have been longstanding challenges in oncology, especially for development of new medications. Solid tumors, unlike hematologic malignancies or brain tumors, are remarkably diverse in their cellular origins and developmental timing. The ability of next-generation sequencing(NGS) to analyze the comprehensive landscape of genetic alterations brings promises to diseases that have a highly complex and heterogeneous genetic composition such as cancer. Here we provide an overview of how NGS is able to facilitate precision medicine and change the paradigm of cancer therapy, especially for solid tumors, through technical advancements, molecular diagnosis, response monitoring and clinical trials.

Development of a quantum-dot-labelled magnetic immunoassay method for circulating colorectal cancer cell detection

AIM:To detect of colorectal cancer(CRC) circulating tumour cells(CTCs) surface antigens,we present an assay incorporating cadmium selenide quantum dots(QDs) in these paper.METHODS:The principle of the assay is the immunomagnetic separation of CTCs from body fluids in conjunction with QDs,using specific antibody biomarkers:epithelial cell adhesion molecule antibody,and monoclonal cytokeratin 19 antibody.The detection signal was acquired from the fluorescence signal of QDs.For the evaluation of the performance,the method under study was used to isolate the human colon adenocarcinoma cell line(DLD-1) and CTCs from CRC patients' peripheral blood.RESULTS:The minimum detection limit of the assay was defined to 10 DLD-1 CRC cells/mL as fluorescence was measured with a spectrofluorometer.Fluorescenceactivated cell sorting analysis and Real Time RT-PCR,they both have also been used to evaluate the performance of the described method.In conclusion,we developed a simple,sensitive,efficient and of lower cost(than the existing ones) method for the detection of CRC CTCs in human samples.We have accomplished these results by using magnetic bead isolation and subsequent QD fluorescence detection.CONCLUSION:The method described here can be easily adjusted for any other protein target of either the CTC or the host.

Molecular pathogenesis and therapeutic strategies of human osteosarcoma

Osteosarcoma（OS）is a devastating illness with rapid rates of dissemination and a poor overall prognosis,despite aggressive standard-of-care surgical techniques and combination chemotherapy regimens.Identifying the molecular mechanisms involved in disease pathogenesis and progression may offer insight into new therapeutic targets.Defects in mesenchymal stem cell differentiation,abnormal expression of oncogenes and tumor suppressors,and dysregulation within various important signaling pathways have all been implicated in development of various disease phenotypes.As such,a variety of basic science and translational studies have shown promise in identifying novel markers and modulators of these disease-specific aberrancies.Born out of these and similar investigations,a variety of emerging therapies are now undergoing various phases of OS clinical testing.They broadly include angiogenesis inhibitors,drugs that act on the bone microenvironment,receptor tyrosine kinase inhibitors,immune system modulators,and other radio-or chemo-sensitizing agents.As new forms of drug delivery are being developed simultaneously,the possibility of targeting tumors locally while minimizing systemic toxicityis is seemingly more achievable now than ever.In this review,we not only summarize our current understanding of OS disease processes,but also shed light on the multitude of potential therapeutic strategies the scientific community can use to make long-term improvements in patient prognosis.

Effects of Neoadjuvant Chemotherapy on Multiple Cytokines in Patients with Tri-negative Breast Cancer

The novel ET therapy is that doxorubicin and paclitaxel are used in neoadjuvant chemotherapy for tri-negative breast cancer(TNBC).The study mainly investigated the efficacy of ET therapy and its impact on tumor markers and cytokines.Firstly extracted from August 2017 to August 2020,84 cases of TNBC patients were as experimental group in our hospital,and the patients were randomly divided into two groups,including the control group(42 cases)underwent conventional chemotherapy and observation group(42 cases)to accept ET neoadjuvant chemotherapy.To compare the therapeutic effect of two groups,levels of cytokines,tumor markers,and survival were detected.The results showed that the total efficiency of the control group was 80.95%,significantly lower than that of the observation group(95.24%),and the difference between the two groups was statistically significant(P<0.05).The survival rate of the control group was 78.57%,which was significantly lower than that of the observation group(95.24%).In addition,CEA,CA19-9,CA125 and VEGF of the control group were significantly higher than those of the observation group(P<0.05).Therefore,the ET therapy of neoadjuvant chemotherapy has an ideal effect on the treatment of TNBC,which can reduce the levels of tumor markers and cytokines,prolonging the survival rate of patients.

Similar fecal immunochemical test results in screening and referral colorectal cancer

AIM: To improve the interpretation of fecal immunochemical test (FIT) results in colorectal cancer (CRC) cases from screening and referral cohorts. METHODS: In this comparative observational study, two prospective cohorts of CRC cases were compared. The first cohort was obtained from 10 322 average risk subjects invited for CRC screening with FIT, of which, only subjects with a positive FIT were referred for colonoscopy. The second cohort was obtained from 3637 subjects scheduled for elective colonoscopy with a positive FIT result. The same FIT and positivity threshold (OC sensor; ≥ 50 ng/mL) was used in both cohorts. Colonoscopy was performed in all referral subjects and in FIT positive screening subjects. All CRC cases were selected from both cohorts. Outcome measurements were mean FIT results and FIT scores per tissue tumor stage (T stage). RESULTS: One hundred and eighteen patients with CRC were included in the present study: 28 cases obtained from the screening cohort (64% male; mean age 65 years, SD 6.5) and 90 cases obtained from the referral cohort (58% male; mean age 69 years, SD 9.8). The mean FIT results found were higher in the referral cohort (829 ± 302 ng/mLvs 613 ± 368 ng/mL,P = 0.02). Tissue tumor stage (T stage) distribution was dif-ferent between both populations [screening population: 13 (46%) T1, eight (29%) T2, six (21%) T3, one (4%) T4 carcinoma; referral population: 12 (13%) T1, 22 (24%) T2, 52 (58%) T3, four (4%) T4 carcinoma], and higher T stage was significantly associated with higher FIT results (P < 0.001). Per tumor stage, no significant difference in mean FIT results was observed (screening vs referral: T1 498 ± 382 ng/mL vs 725 ± 374 ng/mL, P = 0.22; T2 787 ± 303 ng/mL vs 794 ± 341 ng/mL, P = 0.79; T3 563 ± 368 ng/mLvs 870 ± 258 ng/mL,P = 0.13; T4 not available). After correction for T stage in logistic regression analysis, no significant differences in mean FIT results were observed between both types of cohorts (P = 0.10). CONCLUSION: Differences in T stage distribution largely explain differences in FIT results between screening and referral cohorts. Therefore, FIT results should be reported according to T stage.

Asymptomatic pancreatic lesions: New insights and clinical implications

Despite great efforts in experimental and clinical research, the prognosis of pancreatic cancer (PC) has not changed significantly for decades. Detection of pre-invasive lesions or early-stage PC with small resectable cancers in asymptomatic individuals remains one of the most promising approaches to substantially improve the overall outcome of PC. Therefore, screening programs have been proposed to identify curable lesions especially in individuals with a familial or genetic predisposition for PC. In this regard, Canto et al recently contributed an important article comparing computed tomography, magnetic resonance imaging, and endoscopic ultrasound for the screening of 216 asymptomatic high-risk individuals (HRI). Pancreatic lesions were detected in 92 of 216 asymptomatic HRI (42.6%). The high diagnostic yield in this study raises several questions that need to be answered of which two will be discussed in detail in this commentary: First: which imaging test should be performed? Second and most importantly: what are we doing with incidentally detected pancreatic lesions? Which ones can be observed and which ones need to be resected?

Gonadotropin-releasing hormone agonists cotreatment during chemotherapy in borderline ovarian tumor and ovarian cancer patients

Background Recently, conservative surgery is acceptable in young patients with borderline ovarian tumor and ovarian cancer. The preservation of these patients＇ future fertility has been the focus of recent interest. This study aimed to observe the effect of gonadotropin-releasing hormone agonists （GnRHa） cotreatment during chemotherapy in borderline ovarian tumor and ovarian cancer patients. Methods Sixteen patients who were treated with fertility preservation surgery for borderline ovarian tumor and ovarian cancer and then administered GnRHa during chemotherapy in Peking University People＇s Hospital from January 2006 to July 2010 were retrospectively analyzed. This group was compared with a control group of 16 women who were treated concurrently with similar chemotherapy （n=5） without GnRHa or were historical controls （n=11）. The disease recurrence, the menstruation status and reproductive outcome were followed up and compared between the two groups. Results There were no significant differences between both groups regarding age, body weight, height, marriage status, classification of the tumors, stage of the disease, as were the cumulative doses of each chemotherapeutic agent. One （1/16） patient in the study group while 2 （2/16） patients in the control group relapsed 2 years after conclusion of the primary treatment （P 〉0.05）. All of the 16 women in the study group compared with 11 of the 16 patients in the control group resumed normal menses 6 months after the termination of the treatment （P 〈0.05）. There were 4 spontaneous pregnancies in the study group while 2 in the control group, all of the neonates were healthy. Conclusions GnRHa administration before and during chemotherapy in borderline ovarian tumor and ovarian cancer patients who had undergone fertility preservation operation may bring up higher rates of spontaneous resumption of menses and a better pregnancy rate. Long-term follow up and large scale clinical studies are required.

Application of Response Evaluation Criteria of Traditional Chinese Medicine for Solid Tumor in Advanced Non-Small Cell Lung Cancer

Objective：To evaluate the objectivity and comprehensiveness of Response Evaluation Criteria of Traditional Chinese Medicine for Solid Tumor（Draft,REC-TCM-ST） in application of Chinese medicine therapeutic effect in patients with advanced non-small cell lung cancer（NSCLC）.Methods：A retrospective clinical research was used in 104 NSCLC patients in stages of Ⅲ-Ⅳ,53 cases were in Chinese medicine（CM） group and 51 cases were in Western medicine（WM） group.The therapeutic effect of the two groups was evaluated with both REC-TCM-ST and Response Evaluation Criteria in Solid Tumor（RECIST）.Kaplan-Meier method was used to analyze the survival time.Kappa test method was used to test the consistency of the two kinds of evaluation results.Results：According to REC-TCM-ST,the effective rate on relieving tumor mass in the CM group was significantly lower than that in the WM group（P〈0.05）,but there was no significant difference in tumor-mass stable rate（P〉0.05）;the symptom of weakness in the CM group was improved significantly,indicating better therapeutic effect than that in the WM group（P〈0.01）.Karnofsky score in the CM group was significantly better than that in the WM group（P〈0.01）.In terms of survival conditions,the median survival time and the survival rate of 6 months,1 year and 2 years of the CM group were higher than the WM group.The total effective rate was 9.62%,and the total stable rate was 72.12%for 104 cases according to RECIST;while the total effective rate was 34.62%,and the total stable rate was 84.62%according to REC-TCM-ST,thus there were significant differences between the results of the two criteria（P〈0.01）,and there was also some consistency between them,but not satisfactory.Conclusions：REC-TCM-ST was used to evaluate the therapeutic effect of CM in the treatment of advanced NSCLC,which shows that its evaluation results can better reflect the advantages and disadvantages of CM,and the effectiveness of CM is more objective and comprehensive than RECIST,so REC-TCM-ST is worthy of further improvement and clinical expansion.

PROSPECTIVE STUDY OF MULTIPLE GENETIC TUMOR MARKER ASSAY BY QUANTITATIVE REAL-TIME PCR TO PREDICT RECURRENCE IN COLORECTAL CANCER PATIENTS

Objective To describe correlation between multiple genetic tumor markers,carcinoembryonic antigen (CEA),cytokeratin 20 (CK20),and Survivin,and clinicopathological features of colorectal cancer (CRC) and to assess prognostic diagnosis value in cancer recurrence and metastasis.Methods A total of 92 patients with CRC,68 patients with precancerous lesions,and 29 control volunteers were collected for the detection of CEA,CK20,and Survivin expressions by using quantitative Real-Time PCR technology.Associations among these measurements and clinicopathological features of CRC,and cancer recurrence and metastasis rates in 4-year follow-up were analyzed.Results No mRNA expressions of CEA,CK20,or Survivin were detected in the control group.Expressions of CEA,CK20,and Survivin were 41.3%,47.8%,and 72.8% in CRC patients,respectively.The expressions of genetic tumor markers were related to the clinical stage and lymph node metastasis.In patients with Survivin high expression,4-year survival rate was significantly lower than that in Survivin low expression.The multiple tumor markers assay for CRC patients showed higher specificity and positive detection rate than single marker assay.Patients with CEA,CK20,and Survivin simultaneous expressions had significantly higher 4-year recurrence rate and death rate than those with only one or two markers expression.ConclusionMultiple tumor markers assay including CEA,CK20,and Survivin in peripheral blood by quantitative Real-Time PCR can be an ideal method for the surveillance of the recurrence and prognosis for CRC patients.

RNA editingof SLC22A3 causes early tumor progression in familial esophageal cancer patients

Subject Code:H16With the support by the National Natural Science Foundation of China,a collaborative study by the Research groups led by Prof.Fu Li(付利)from the Cancer Research Center,Shenzhen University School of Medicine and Prof.Guan Xinyuan(关新元)from the University of Hong Kong reported that an

Glucocorticoids suppress tumor angiogenesis and growth of prostate cancer

Hormone-refractory prostate cancer ( HRPC) sometimes is responsive to treatment with glucocorticoids, such as prednisolone, hydrocortisone and dexamethasone, but the underlying mechanisms are not well established. In a recent paper (Clin Cancer Res, 2006, 12:3003-3009), Yano et al. Hypothesized and confirmed that the therapeutic effect of glucocorticoids on HRPC is attributed to inhibition of angiogenesis. A prostate cancer cell line DU145 that expresses glucocorticoid receptor was used to study the effect of dexamethasone (Dex) on the expres-

Phase 1 clinical trial demonstrated that MUC1 positive metastatic seminal vesicle cancer can be effectively eradicated by modified Anti-MUC1 chimeric antigen receptor transduced T cells

Recent progress in chimeric antigen receptor-modified T-cell(CAR-T cell) technology in cancer therapy is extremely promising, especially in the treatment of patients with B-cell acute lymphoblastic leukemia. In contrast, due to the hostile immunosuppressive microenvironment of a solid tumor, CAR T-cell accessibility and survival continue to pose a considerable challenge, which leads to their limited therapeutic efficacy. In this study, we constructed two anti-MUC1 CAR-T cell lines. One set of CAR-T cells contained SM3 single chain variable fragment(sc Fv) sequence specifically targeting the MUC1 antigen and co-expressing interleukin(IL) 12(named SM3-CAR). The other CAR-T cell line carried the SM3 sc Fv sequence modified to improve its binding to MUC1 antigen(named p SM3-CAR) but did not co-express IL-12. When those two types of CAR-T cells were injected intratumorally into two independent metastatic lesions of the same MUC1+ seminal vesicle cancer patient as part of an interventional treatment strategy, the initial results indicated no side-effects of the MUC1 targeting CAR-T cell approach, and patient serum cytokines responses were positive. Further evaluation showed that p SM3-CAR effectively caused tumor necrosis, providing new options for improved CAR-T therapy in solid tumors.

Nicotinamide N-methyltransferase protein expression in renal cell cancer

Objective: To understand the function of nicotinamide N-methyltransferase (NNMT) protein as tumor biomarker in renal carcinoma. Methods: Recombinant NNMT protein was used to prepare monoclonal antibodies by hybridoma technique. The diagnostic and prognostic function of NNMT protein in renal carcinoma was evaluated by analyzing 74 renal cancer tissues through immunohistochemical staining for NNMT by using the prepared antibodies. Results: Two hybridomas named 2F8 and 1E7 stably secreting the monoclonal antibodies were isolated successfully, and characters such as isotypes and specificity were determined. NNMT protein was significantly up-regulated in renal cancer and significantly associated with tumor histology and ages. The univariate survival analysis demonstrated that the pT-status, high levels of NNMT, and distant metastasis were significant prognosticators. Conclusion: NNMT is over-expressed in a large proportion in renal cell cancers. High NNMT expression is significantly associated with unfavorable prognosis. However, the prognostic value of NNMT needs further verification in larger sample sizes.