Clinical Observation of Arteriovenous Combined Chemotherapy in Advanced Gastric Cancer

Objective:To analyze the therapeutic effect and influencing factors of arteriovenous combined chemotherapy in 39 patients with advanced gastric cancer,and to explore the choice of therapeutic strategy.Methods:In this group of patients,the sequence of combined use of arteriovenous chemotherapy was 2 cycles of arterial chemotherapy first,followed by 3~4 cycles of systemic intravenous chemotherapy,and then changed to traditional Chinese medicine,oral chemotherapeutic drugs or immunotherapy after stable disease.Results:Thirty-five patients achieved complete disappearance of symptoms,significant tumor reduction of 26%(PR:13/39),moderate tumor reduction of 51%,18 patients with tumor markers decreased by more than 50%,4 patients completely reduced to normal,half-year survival rate of 90%,1-year survival rate of 56%,3-year survival rate of 33%,5-year survival rate of 10%.Conclusion:The use of arteriovenous combined chemotherapy and embolization in patients with middle and advanced gastric cancer is not only feasible,but also less complications.It can enable some patients to achieve stage II surgical resection,reduce or delay the metastasis and recurrence of patients,improve the quality of life of patients and prolong the survival time.

Pneumatosis Cystoides Intestinalis Complicated during Chemotherapy for Pulmonary Nontuberculous Mycobacterial Disease

Background: Pneumatosis cystoides intestinalis (PCI) is a rare disease characterized by the presence of gas in the intestinal wall. Aim: We report two rare cases of PCI that are complicated during the chemotherapy for pulmonary nontuberculous mycobacterial (NTM) disease. Case Presentation: In this report, we described two cases (a 72-year-old woman and a 60-year-old woman) of PCI that appeared during the combined chemotherapy consisting of rifampicin, ethambutol and clarithromycin. Because there were few clinical symptoms and increased inflammatory responses, the diagnosis of PCI was delayed. However, there were fortunately no severe complications in both cases. Conclusion: Respiratory physicians should be aware of the potential development of PCI in patients during the chemotherapy for pulmonary NTM disease. It is important to detect PCI in the early stage through radiological examinations to avoid severe complications.

Local immunotherapy with interleukin - 2 delivered from biodegradable polymer microspheres combined with interstitial chemotherapy: a novel treatment for experimental malignant glioma.

OBJECTIVE:Local delivery of carmustine(BCNU)from biodegradablepolymers prolongs survival against experi-mental brain tumors.Moreover,paracrine administration of interleukin-2(IL-2)has been shown to elicit apotent antitumor immune response and to improve survival in animal brain tumor models.We report the use of anovel polymeric microsphere delivery vehicle to release IL-2.We demonstrate both in vitro release of cytokinefrom the microspheres and histological evidence of the inflammatory response elicited by IL-2 released from themicrospheres in the rat brain.Thees microspheres are used to deliver IL-2,and biodegradable polymer wafers

Natural product-induced oxidative stress-synergistic anti-tumor effects of chemotherapeutic agents

Reactive oxygen species are closely related to tumor development.In recent years,reactive oxygen species has become a hot spot in tumor therapy,and many natural substances in nature contain compound components with anti-tumor effects.However,there is a lack of discussion on the synergistic anti-tumor effects of natural products in combination with chemotherapeutic drugs through reactive oxygen species.The terms“natural products”,“reactive oxygen species”,“anti-tumor”,and“chemotherapy”were used to identify the synergistic effects of natural products.We conducted a systematic literature search in PubMed and Web of Science databases for relevant research articles and reviews published in recent years.We systematically summarized the studies related to anti-tumor active ingredients in natural compounds in the field of reactive oxygen species in recent years.A total of 77 relevant literatures were included.Among them,45 literatures containing various natural products such as terpenoids,flavonoids,alkaloids,etc.exert anti-tumor effects by regulating reactive oxygen species levels,and 32 literatures regarding adjunctive role of natural products in anti-tumor therapy.In this study,we found that natural products exert anti-tumor effects by elevating reactive oxygen species levels.It provides strong theoretical support for future clinical studies.

Hormonal therapy might be a better choice as maintenance treatment than capecitabine after response to first-line capecitabine-based combination chemotherapy for patients with hormone receptor-positive and HER2-negative,metastatic breast cancer

Background:Both hormonal therapy(HT) and maintenance capecitabine monotherapy(MCT) have been shown to extend time to progression(TTP) in patients with metastatic breast cancer(MBC) after failure of taxanes and anthracycline?containing regimens.However,no clinical trials have directly compared the efficacy of MCT and HT after response to first?line capecitabine?based combination chemotherapy(FCCT) in patients with hormone receptor(HR)?positive and human epidermal growth factor receptor 2(HER2)?negative breast cancer.Methods:We retrospectively analyzed the charts of 138 HR?positive and HER2?negative MBC patients who were in non?progression status after FCCT and who were treated between 2003 and 2012 at the Cancer Institute and Hospital,Chinese Academy of Medical Sciences,in Beijing,China.The median number of first?line chemotherapy cycles was 6(range,4–8);combined agents included taxanes,vinorelbine,or gemcitabine.Of these 138 patients,79 received MCT,and 59 received HT.Single?agent capecitabine was administered at a dose of 1250 mg/m2 twice daily for 14 days,followed by a 7?day rest period,repeated every 3 weeks.Of the 59 patients who received HT,37 received aromatase inhibitors(AIs),8 received selective estrogen receptor modulators(SERMs),and 14 received goserelin plus either AIs or SERMs.We then compared the MCT group and HT group in terms of treatment efficacy.Results:With a median follow?up of 43 months,patients in the HT group had a much longer TTP than patients in the MCT group(13 vs.8 months,P ease?free surviv= 0.011).When TTP was adjusted for age,menopausal status,Karnofsky performance status score,disal,site of metastasis,number of metastatic sites,and response status after FCCT,extended TTP was still observed for patients in the HT group(hazard ratio:0.63;95% confidence interval:0.44–0.93;P = 0.020).We also observed a trend of overall survival advantage for patients in the HT group vs.patients in the MCT group,but the difference was not significant(43 vs.37 months,P tients in the MCT g= 0.400).In addition,patients in the HT group gen?erally tolerated the treatment well,whereas paroup experienced grades 3–4 adverse events,the most frequent of which were hand?foot syndrome(15.8%) and hematologic abnormalities(7.6%).Conclusion:For HR?positive and HER2?negative MBC patients,HT might be considered a treatment after response to FCCT but prior to MCT as a long?term administration.

First-line chemotherapy in very elderly patients with metastatic pancreatic cancer:Gemcitabine monotherapy vs combination chemotherapy

BACKGROUND Combination chemotherapy(gemcitabine plus nab-paclitaxel and FOLFIRINOX)is widely used as the standard first-line treatment for pancreatic cancer.Considering the severe toxicities of combination chemotherapy,gemcitabine monotherapy(G mono)could be used as a first-line treatment in very elderly patients or those with a low Eastern Cooperative Oncology Group status.However,reports on the efficacy of G mono in patients older than 75 years are limited.AIM To evaluate the efficacy of G mono and combination chemotherapy by comparing their clinical outcomes in very elderly patients with pancreatic cancer.METHODS We retrospectively analyzed 104 older patients with pancreatic cancer who underwent chemotherapy with G mono(n=45)or combination therapy(n=59)as a first-line treatment between 2011 and 2019.All patients were histologically diagnosed with ductal adenocarcinoma.Primary outcomes were progression-free survival and overall survival.We also analyzed subgroups according to age[65-74 years(elderly)and≥75 years(very elderly)].Propensity score matching was performed to compare the outcomes between the two chemotherapy groups.RESULTS The baseline characteristics were significantly different between the two chemotherapy groups,especially regarding age,ratio of multiple metastases,tumor burden,and Eastern Cooperative Oncology Group performance status.After propensity score matching,the baseline characteristics were not significantly different between the chemotherapy groups in elderly and very elderly patients.In the elderly patients,the median progression-free survival(62 d vs 206 d,P=0.000)and overall survival(102 d vs 302 d,P=0.000)were longer in the combination chemotherapy group.However,in the very elderly patients,the median progression-free survival(147 d and 174 d,respectively,P=0.796)and overall survival(227 d and 211 d,respectively,P=0.739)were comparable between the G mono and combination chemotherapy groups.Adverse events occurred more frequently in the combination chemotherapy group than in the G mono group,especially thromboembolism(G mono vs nab-paclitaxel vs FOLFIRINOX;8.9%vs 5.9%vs 28%,P=0.041),neutropenia(40.0%vs 76.5%vs 84.0%,P=0.000),and neuropathy(0%vs 61.8%vs 28.0%,P=0.006).CONCLUSION In elderly patients,combination therapy is more effective than G mono.However,G mono is superior for the management of metastatic pancreatic cancer in very elderly patients.

Using Pegaspargase in Combination with Chemotherapy in the Treatment of Lymphoma

Objective:To analyze the clinical effect of pegaspargase combined with chemotherapy on patients with lymphoma.Methods:Seventy patients with lymphoma admitted to Shaanxi Provincial People’s Hospital between December 2020 and June 2021 were selected as study subjects and were equally divided into the control group and the intervention group using the lottery method,with 35 cases in each group;the control group received conventional treatment,while the intervention group received pegaspargase combined with chemotherapy.The treatment satisfaction,quality of life,psychological status,and incidence of adverse reactions of the patients in the two groups were compared.Results:The differences in the indicators between the two groups were statistically significant(p<0.05).Conclusion:Pegaspargase combined with chemotherapy can effectively improve the treatment effect and satisfaction of lymphoma patients;hence,it is worthy of promotion in clinical treatment.

Successful treatment of a high-risk nonseminomatous germ cell tumor using etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine: A case report

BACKGROUND Choriocarcinoma is an infrequent entity and the most aggressive subtype of germcell tumors.Because of early metastatic spread and rapid disease progression,choriocarcinoma patients display poor prognosis.Although etoposide,methotrexate,actinomycin D,cyclophosphamide,and vincristine(EMA-CO)regimen is widely used to treat gestational trophoblastic tumors in females,its role in treating male choriocarcinoma is seldom reported.CASE SUMMARY A 32-year-old man was diagnosed with burned-out primary germ cell tumors(GCT)with retroperitoneum,liver and lung metastases.Biopsy of the liver revealed pure choriocarcinoma.The patient received bleomycin,etoposide,and cisplatin chemotherapy.After two cycles of treatment,response evaluation revealed the mixed response.EMA-CO regimen was used in the second-line therapy.After eight cycles,the patient showed a potentially resectable state and thus,all residual masses were surgically removed.The patient was completely cured,and 10 years later,he is leading a healthy life without complications.CONCLUSION This paper is the first case of high-risk nonseminomatous GCT in a male patient to be successfully treated with the EMA-CO regimen.The EMA-CO regimen can be used actively in patients with high-risk nonseminomatous GCT.

Hepatic epithelioid hemangioendothelioma after thirteen years'follow-up:A case report and review of literature

BACKGROUND Hepatic epithelioid hemangioendothelioma(EHE)is a rare vascular endothelial cell tumor of the liver,consisting of epithelioid and histiocyte-like vascular endothelial cells in mucus or a fibrotic matrix.Immunohistochemistry is usually positive for vascular markers,such as factor VIII-related antigen,CD31,and CD34.Hepatic EHE can have a varied clinical course;treatment includes liver transplantation,liver resection,chemotherapy,and radiation therapy.CASE SUMMARY A 46-year-old woman with abdominal discomfort and elevated serum carcinoembryonic antigen was found to have multiple low-density lesions in the liver and lung on computed tomography(CT)evaluation.An ultrasound-guided fine needle aspiration biopsy revealed a fibrous stroma with dendritic cells,containing intracellular vacuoles.Immunohistochemical staining found that the tumor cells were positive for CD34,CD31,and factor VIII-related antigen.The patient received four courses of combined chemotherapy and was followed-up for 13 years,at which time the patient was in stable condition without disease progression and a confined neoplasm,as evidenced by CT scans.CONCLUSION The histology and immunohistochemical characteristics of hepatic EHE are well described.Chemotherapy may be effective in patients with extrahepatic lesions.

Clinical outcomes of targeted therapies in elderly patients aged ≥ 80 years with metastatic colorectal cancer

BACKGROUND The 5-fluorouracil-based chemotherapy combined with oxaliplatin or irinotecan is usually used in colorectal cancer(CRC).The addition of a targeted agent(TA) to this combination chemotherapy is currently the standard treatment for metastatic CRC.However,the efficacy and safety of combination chemotherapy for metastatic CRC in patients aged above 80 years has yet to be established.AIM To assess the clinical outcomes and feasibility of combination chemotherapy using a TA in extremely elderly patients with CRC.METHODS Eligibility criteria were:(1) Age above 80 years;(2) Metastatic colorectal cancer;(3) Palliative chemotherapy na?ve;(4) Eastern Cooperative Oncology Group performance status 0-1;and(5) Adequate organ function.Patients received at least one dose of combination chemotherapy with or without TA.Response was evaluated every 8 wk.RESULTS Of 30 patients,the median age of 15 patients treated with TA was 83.0 years and that of those without TA was 81.3 years.The median progression-free survival(PFS) and overall survival(OS) in patients treated with TA were 7.4 mo and 15.4 mo,respectively,compared with 4.4 mo and 15.6 mo,respectively,in patients treated without TA.There was no significant difference in PFS(P:0.193) and OS(P:0.748) between patients treated with and without TA.Common grade 3/4 hematologic toxicities were anemia(16.7%) and neutropenia(10.0%).After disease progression,the median OS of patients who were treated with and without salvage chemotherapy were 23.5 mo and 7.0 mo,respectively,suggesting significant difference in OS(P = 0.001).CONCLUSION Combination chemotherapy with TA for metastatic CRC may be considered feasible in patients aged above 80 years,when with careful caution.Salvage chemotherapy can help improve OS in some selected of these elderly patients.

ADVANCE NON SMALL CELL LUNG CANCER ACCEPTING CHEMOTHERAPY COMBINED WITH SHENMAI INJECTION

The aim of the study was to observe the changes of vascular endothelial growth factor(VEGF)and the efficacy of patients with advanced non-small-cell lung cancer(NSCLC)after the treatment of chemotherapy with Shenmai Injection.This study is a randomized controlled,prospective,single blind trial.63 eligible patients with NSCLC were

Evaluation of the Efficiency of the Magicramp® Device for Reducing Cramps Resulting from Oncological Treatments: “Double-Blind, Randomized Clinical Trial”

We identified that oncological treatments in general (chemotherapies, immunotherapies and radiotherapies) frequently cause peripheral neuropathy, including cramps, characterized by excess protons due to metabolic and neuronal factors, such as sudden changes in pH, uremia and aspects that affect neuromotor functions. Such situations and others like them are often neglected in treatment, which naturally concerns itself with the main problem: Cancer. Sometimes toxic solutions are implemented that have comorbid side effects, such as duloxetine (standard treatment). Based on monitoring of cancer patients who used the non-toxic product, called “Magicramp® Electrostatic Charge Reduction Cushion” (MECRC), approved in Europe more than 10 years ago, we carried out a controlled test in Brazil. In this clinical trial, we hypothesized that reducing excessive ionic charges (electrostatic charge), which is one of the side effects often described in the literature as “Chemotherapy-Induced Peripheral Neuropathy” (CIPN), would decrease or eliminate cramping, under the hypothesis that such elimination would prevent or attenuate muscular vulnerability to action impulses, and increase the power of relaxation through the same mechanism. In this double-blind and randomized clinical trial, 40 (forty) adult patients with muscle cramps caused by oncological treatments were tested, evaluating the degree of efficiency of the product that aims to reduce muscle cramps, by eliminating and/or reducing excess loads electrostatic ionic. Data from the clinical research conducted in this study are available online at https://doi.org/10.7910/DVN/QUS94U.

Polyoxypregnanes as safe, potent, and specific ABCB1-inhibitory pro-drugs to overcome multidrug resistance in cancer chemotherapy in vitro and in vivo

Multidrug resistance(MDR)mediated by ATP binding cassette subfamily B member 1(ABCB1)is significantly hindering effective cancer chemotherapy.However,currently,no ABCB1-inhibitory drugs have been approved to treat MDR cancer clinically,mainly due to the inhibitor specificity,toxicity,and drug interactions.Here,we reported that three polyoxypregnanes(POPs)as the most abundant constituents of Marsdenia tenacissima(M.tenacissima)were novel ABCB1-modulatory pro-drugs,which underwent intestinal microbiota-mediated biotransformation in vivo to generate active metabolites.The metabolites at non-toxic concentrations restored chemosensitivity in ABCB1-overexpressing cancer cells via inhibiting ABCB1 efflux activity without changing ABCB1 protein expression,which were further identified as specific non-competitive inhibitors of ABCB1 showing multiple binding sites within ABCB1 drug cavity.These POPs did not exhibit ABCB1/drug metabolizing enzymes interplay,and their repeated administration generated predictable pharmacokinetic interaction with paclitaxel without obvious toxicity in vivo.We further showed that these POPs enhanced the accumulation of paclitaxel in tumors and overcame ABCB1-mediated chemoresistance.The results suggested that these POPs had the potential to be developed as safe,potent,and specific pro-drugs to reverse ABCB1-mediated MDR.Our work also provided scientific evidence for the use of M.tenacissima in combinational chemotherapy.

Self-Motivated Supramolecular Combination Chemotherapy for Overcoming Drug Resistance Based on Acid-Activated Competition of Host–Guest Interactions

In this work,we propose a nanoparticle-based strategy of self-motivated supramolecular combination chemotherapy that carries drugs stably and releases them actively in the acidic tumor microenvironment to overcome the drug resistance of cancer cells.This self-motivated nanoparticle consists of a cucurbit[7]uril-containing polymer(PCB)-based core.

Cisplatin and paclitaxel co-delivery nanosystem for ovarian cancer chemotherapy

We have designed and developed an effective drug delivery system using biocompatible polymer of poly(ethylene glycol)-polyaspartic acid(mPEG-PAsp)for co-loading the chemotherapy drugs paclitaxel(PTX)and cisplatin(CP)in one nano-vehicle.This study aimed to improve the anti-cancer effi-cacy of combinations of chemotherapy drugs and reduce their side effects.mPEG-PAsp-(PTX/Pt)nano-micelles disperse well in aqueous solution and have a narrow size distribution(37.863.2 nm)in dynamic light scattering(DLS).Drug release profiles found that CP released at pH 5.5 was signifi-cantly faster than that at pH 7.4.MPEG-PAsp-(PTX/Pt)nano-micelles displayed a significantly higher tumor inhibitory effect than mPEG-PAsp-PTX nano-micelles when the polymer concentrations reached 50 lg/mL.Our data indicated that polymer micelles of mPEG-PAsp loaded with the combined drug exert synergistic anti-tumor efficacy on SKOV3 ovarian cells via different action mechanisms.Results from our studies suggested that mPEG-PAsp-(PTX/Pt)nano-micelles are promising alternatives for carrying and improving the delivery of therapeutic drugs with different water solubilities.

The Chinese guidelines for neoadjuvant therapy of pancreatic cancer(2020)

Aiming to keep pace with the renewal of international guidelines and refine the domestic treatment system of pancreatic cancer,the Chinese Pancreatic Surgery Association,Chinese Medical Association and Pancreatic Disease Committee of China Research Hospital Association launched this Chinese guidelines for neoadjuvant therapy of pancreatic cancer(2020 edition).Based on the Grading of Recommendations Assessment,Development,and Evaluation system,the guidelines have conducted a discussion on the indication,regimen selection,therapeutic effect evaluation,pathological diagnosis,surgery strategy,etc.The guidelines have quantified the evidence level of the current clinical researches and provided recommendations for the clinical practice in neoadjuvant therapy of pancreatic cancer.The guidelines have highlighted the role of multiple disciplinary team and represented the conversion of treatment concepts in pancreatic cancer.Neoadjuvant therapy has prolonged the survival of part of pancreatic cancer patients.However,more high-quality clinical researches are in urgent need to improve the level of evidence,optimize the clinical practice,and improve the survival of patients.

Echinatin inhibits tumor growth and synergizes with chemotherapeutic agents against human bladder cancer cells by activating p38 and suppressing Wnt/β-catenin pathways

Bladder cancer (BC) is one of the most common malignant tumors in the urinary system.Due to the poor prognosis and high mortality rate of the disease,it is urgent to develop new drugs with high efficacy and low toxicity to treat BC.Echinatin (Ecn) is a bioactive natural flavonoid oflicorice that has attracted special attention for its promising anti-tumor potential.Herein,we explored the inhibitory effects of Echinatin on BC cells and probed the possible molecular mechanism.We found that Ecnin vitro inhibited the proliferation,migration,and invasion,arrested the cell cycle at the G2/M phase,and promoted apoptosis in BC cells.Besides,Ecn had no notable cytotoxicity towards human normal cells.We subsequently confirmed that Ecn restrained xenograft tumor growth and metastasis of BC cells in vivo .Mechanistically,Ecn activated the p38 signaling pathway but inactivated the Wnt/β-catenin signaling pathway,while over-expression of β-catenin and the p38 inhibitor both attenuated the inhibitory effects of Ecn on BC cells.Remarkably,Ecn combined with cisplatin (DDP) or gemcitabine (Gem) had synergistic inhibitory effects on BC cells.In summary,our results validate that Ecn inhibits the tumor growth of human BC cells via p38 and Wnt/β-catenin signaling pathways.More meaningfully,our results suggest a potential strategy to enhance DDP- or Gem-induced inhibitory effects on BC cells by combining with Ecn.