Differential recovery of polymorphonuclear neutrophils,B and T cell subpopulations in the thymus,bone marrow,spleen and blood of mice following split-dose polychemotherapy

In these studies, we examined the effect of a maximum-tolerated, split-dose chemotherapy protocol of cyclophosphamide, cisplatin, and 1,3-bis(2-chloroethyl)-1-nitrosourea carmustine on neutrophil and lymphocyte subpopulations in the peripheral blood (PBL), thymus, bone marrow and spleen. It was found that this protocol of polychemotherapy, modeled after the induction protocol used with autologous bone marrow transplantation for breast cancer, suppressed both B and T cell populations and T cell function at times when the absolute neutrophil count had returned to normal or supernormal numbers. In the peripheral blood, 7 days following initiation of chemotherapy, there was a twofold increase in the percentage of granulocytes as compared to the level in control animals on the basis of a differential count. The polymorphonuclear neutrophil (PMN) frequency in the bone marrow was increased on day 14 and statistically identical to that in control mice on all other days analyzed. In contrast to the bone marrow cells and PBL on day 7, the frequency of PMN in the spleen and thymus was depressed. B cells (B220+) were depressed in the PBL, spleen and bone marrow and took 18–32 days to return to their normal frequency, while the frequency of B cells in the thymus was increased owing to a loss of immature T cells. The percentage of CD3+ cells in the thymus, spleen and bone marrow was significantly increased and required 10–18 days to return to normal levels, while the absolute number of CD3+ cells in the blood varied around the normal value. The ratio of CD4+ to CD8+ cells in all the organs studied varied only slightly owing to a similar reconstitution of CD4+ and CD8+ cells. In contrast to the phenotypic recovery of the CD3+, CD4+ and CD8+ cells, the ability of the splenic lymphocytes to respond to concanavalin-A was depressed and remained depressed, despite the phenotypic reconstitution of the T cell subsets, on the basis of both percentage and absolute cell number. These results show a selective T and B cell depression following multi-drug, split-dose chemotherapy in tissue and blood leukocyte populations and a chronic depression in T cell function.     

Eimeria tenella: specific reversal of t-butylaminoethanol toxicity for parasite and host by choline and dimethylaminoethanol.

t-Butylaminoethanol is an anticoccidial compound that is related structurally to the metabolically active substances, dimethylaminoethanol, and choline. Toxic effects of t-butylaminoethanol for chickens and Eimeria tenella are specifically overcome by feeding sufficient amounts of dimethylaminoethanol or choline. Dietary concentrations of the two above metabolites required to totally overcome toxic effiects of t-butylaminoethanol were determined and are expressed as the reversal ratio, inhibitor (t-butylamino-ethanol): metabolite. The inhibitor:choline ratio for total reversal of toxic effects of the inhibitor in chickens is approximately 1:10 over a concentration range of inhibitor from 0.019 to 0.05%. The inhibitor:choline ratio for reversal of antiparasitic effects is approximately 1:200 with a concentration of 0.01% inhibitor. The inhibitor:Dimethylaminoethanol ratio for reversal of toxic effects of the inhibitor in the chicken is approximately 1:7 with a concentration of 0.015% inhibitor. The inhibitor:dimethylaminoethanol ratio for reversal of antiparasitic effects is approxmately 1:20 wth a concentration of 0.01% inhibitor.     

Babesia bigemina,Babesia argentina, and Anaplasma marginale: Coinfectious immunity in bovines

Forty-eight intact and eight splenectomized cattle were used to evaluate different systems of coinfectious immunization against Babesia bigemina, Babesia argentina, and Anaplasma marginale. Coinfectious immunity was induced by two methods: (1) blood of cattle acutely infected with B. bigemina, B. argentina and A. marginale was used as the source of inoculum and the post vaccination reactions were chemotherapeutically controlled with Imidocarb, Ganaseg, Gloxazone, and Liquamycin, and (2) by artificially inducing babesiosis with the blood of carrier cattle with chronic infections of B. bigemina and B. argentina without chemotherapy. The degree of resistance was determined by bloodborne and tick-borne challenges. Ticks were collected from cattle and identified as Boophilus microplus and Dermacentor nitens. Vaccinated cattle demonstrated a high degree of resistance to babesiosis and anaplasmosis; however, cattle without coinfectious immunity were treated chemotherapeutically to prevent death losses.     

Trypanosoma brucei: An evaluation of salicylhydroxamic acid as a trypanocidal drug

The chemotherapeutic potential of salicylhydroxamic acid (SHAM) was studied in adult rats infected with a strain of Trypanosoma brucei that kills the rats in about 100 hr. The median lethal dose, administered intraperitoneally in a carboxymethyl-cellulose suspension, is approximately 820 mg/kg body weight for male and 850 mg/kg for female rats. The apparent cause of death is severe depression of the central nervous system.Half-maximal inhibition of O₂ uptake by trypanosomes in vitro requires 15 μM SHAM, whereas 100 μM inhibits over 90%. This inhibitory effect on trypanosome respiration was used as a biological assay for the effective SHAM concentration in rat plasma. After administration of a sublethal SHAM dose to rats, the effective plasma SHAM concentration rose rapidly to about 500 μM and then fell to about 10 μM at 4 hr. Nevertheless, this dose did not significantly affect the survival time of rats infected with T. brucei. Even if, by repeated SHAM administration, the plasma SHAM concentration was kept at around 100 μM for more than 4 hr, no therapeutic effect was observed.These results show that O₂ uptake is not essential for the survival of trypanosomes in rats and they support the idea that bloodstream trypanosomes have an alternative pathway for glycolysis, allowing energy production in the absence of respiration.The possibility that SHAM or other inhibitors of trypanosome respiration could stilll be trypanocidal if used in conjunction with another inhibitor of glycolysis is discussed.     

益生菌在结直肠癌患者中的应用

结直肠癌(colorectal cancer,CRC)的发病率及病死率在多国多年居高不下,肠道微生态的失衡在CRC的发生发展中所起的作用被许多学者所证实。专家一致认为,积极纠正肠道微生态失衡是可取的。CRC患者术前肠道菌群已经出现改变,术后肠道菌群失衡加重,化疗会进一步加重这种失衡状态。肠道微生态的稳态对机体肠道功能和免疫功能等起着重要作用。益生菌作为一种可调节肠道菌群的微生态制剂,已显现出在CRC患者治疗中的应用价值,现对益生菌在CRC患者中的应用进展作一综述。     

Targeting head and neck tumoral stem cells: From biological aspects to therapeutic perspectives

Head and neck squamous cell cancer(HNSCC) is the sixth most common cancer in the world. Effective therapeutic modalities such as surgery, radiation, chemotherapy and combinations of each are used in the management of the disease. In most cases, treatment fails to obtain total cancer cure. In recent years, it appears that one of the key determinants of treatment failure may be the presence of cancer stem cells(CSCs) that escape currently available therapies. CSCs form a small portion of the total tumor burden but may play a disproportionately important role in determining outcomes. CSCs have stem features such as self-renewal, high migration capacity, drug resistance, high proliferation abilities. A large body of evidence points to the fact that CSCs are particularly resistant to radiotherapy and chemotherapy. In HNSCC, CSCs have been increasingly shown to have an integral role in tumor initiation, disease progression, metastasis and treatment resistance. In the light of such observations, the present review summarizes biological characteristics of CSCs in HNSCC, outlines targeted strategies for the successful eradication of CSCs in HNSCC including targeting the self-renewal controlling pathways, blocking epithelial mesenchymal transition, niche targeting, immunotherapy approaches and highlights the need to better understand CSCs biology for new treatments modalities.     

Suramin Induces Phosphorylation of the High-Affinity Nerve Growth Factor Receptor in PC12 Cells and Dorsal Root Ganglion Neurons

Abstract: Suramin is a polysulfonated naphthylurea with demonstrated antineoplastic activity. Toxicity includes adrenal insufficiency and peripheral neuropathy. Although the mechanism of antitumor activity is unknown, inhibition of binding of growth factors to their receptors has been suggested. Growth factors inhibited by suramin include platelet-derived growth factor, fibroblast growth factor, transforming growth factor, epidermal growth factor, insulin-like growth factor, and nerve growth factor (NGF). In these studies, suramin was shown to be cytotoxic to PC12 cells in a dose-dependent manner. At lower doses and in surviving cells, we observed the induction of neurite outgrowth. To determine the mechanism of suramin-induced neurite outgrowth, PC12 cells were exposed to suramin and/or NGF for various time periods and treated cells were analyzed, by western blot analysis, for expression of tyrosine phosphoproteins. There was a similarity in the pattern of tyrosine-phosphorylated proteins in PC12 cells stimulated with suramin or NGF. Of particular interest was the rapid phosphorylation (by 1 min) of the high-affinity NGF (TrkA) receptor. Activation of other members of the signal-transduction cascade (Shc, p21 ^ras , Raf-1, ERK-1) revealed similar phosphorylation levels induced by suramin and NGF. Parallel studies were performed in rat dorsal root ganglion cultures; suramin potentiated neurite outgrowth and activated the NGF receptor on these cells. This finding of specific patterns of tyrosine phosphorylation of cellular proteins in response to suramin treatment demonstrated that suramin is a partial agonist for the NGF receptor in both PC12 cells and dorsal root ganglion neurons.     

卡瑞利珠单抗联合化疗对晚期非鳞非小细胞肺癌患者免疫功能和NLR、CAR的影响

摘要 目的：探讨卡瑞利珠单抗联合化疗对晚期非鳞非小细胞肺癌（NSCLC）患者免疫功能和中性粒细胞与淋巴细胞比值（NLR）、C-反应蛋白与白蛋白比值（CAR）的影响。方法：采用回顾性分析,选取2020年1月到2022年12月期间安徽医科大学第一附属医院北区收治的晚期非鳞NSCLC患者100例,按照治疗方法将患者分为对照组（n=48）和观察组（n=52）。对照组接受注射用培美曲塞二钠联合顺铂注射液或注射用奈达铂化疗,观察组在对照组基础上接受卡瑞利珠单抗治疗。对比两组疗效、免疫功能、肿瘤标志物、NLR、CAR,同时观察两组治疗期间不良反应发生率。结果：与对照组相比,观察组的临床总有效率更高（P<0.05）。治疗4个周期后,与对照组相比,观察组癌胚抗原（CEA）、细胞角蛋白19片段抗原21-1（CYFRA21-1）、糖类抗原125（CA125）、NLR、CAR、CD8⁺更低,CD3⁺、CD4⁺、CD4⁺/CD8⁺更高（P<0.05）。两组不良反应发生率对比未见差异（P>0.05）。结论：晚期非鳞NSCLC患者在化疗的基础上结合卡瑞利珠单抗治疗,有助于控制疾病进展,提高临床疗效,降低肿瘤标志物水平,提高免疫功能,降低NLR、CAR。     

血清ANXA2、ANXA3与转移性结直肠癌患者化疗疗效的关系

摘要 目的：探讨血清膜联蛋白（ANX）A2、ANXA3与转移性结直肠癌（mCRC）患者化疗疗效的关系。方法：选取2019年1月～2020年10月徐州医科大学附属医院收治的90例mCRC患者,根据mFOLFOX6化疗联合西妥昔单抗治疗后的疗效分为未缓解组和缓解组。采用酶联免疫吸附法检测血清ANXA2、ANXA3水平。分别采用单因素、多因素Logistic回归分析和受试者工作特征（ROC）曲线分析mCRC患者化疗未缓解的影响因素和血清ANXA2、ANXA3对mCRC患者化疗未缓解的预测价值。结果：90例mCRC患者客观缓解率为58.89%（53/90）。单因素分析显示,两组年龄、回盲部肿瘤、TNM分期、Zubrod-东部肿瘤协助组-世界卫生组织（ZPS）评分、治疗目标、ANXA2、ANXA3组间比较存在统计学差异（P＜0.05）。多因素Logistic回归分析显示,回盲部肿瘤、TNM分期Ⅳ期、ZPS评分1～2分和ANXA2、ANXA3升高为mCRC患者化疗未缓解的独立危险因素（P＜0.05）。ROC曲线分析显示,血清ANXA2预测mCRC患者化疗未缓解的曲线下面积（AUC）为0.787,ANXA3预测mCRC患者化疗未缓解的AUC为0.791,血清ANXA2、ANXA3联合预测为0.904,二者联合预测的AUC最大（P＜0.05）。结论：血清ANXA2、ANXA3水平升高为mCRC患者化疗未缓解的独立危险因素,可影响mCRC患者的化疗疗效,二者联合预测mCRC患者化疗未缓解的价值较高。     

COVID-19 pandemic and patients with cancer: The protocol of a Clinical Oncology center in Tehran,Iran

AimTo provide recommendations for the management of patients with cancer in the COVID-19 era.BackgroundThe current global pandemic of COVID-19 has severely impacted global healthcare systems. Several groups of people are considered high-risk for SARS-CoV-2 infection, including patients with cancer. Therefore, protocols for the better management of these patients during this viral pandemic are necessary. So far, several protocols have been presented regarding the management of patients with cancer during the COVID-19 pandemic. However, none of them points to a developing country with limited logistics and facilities.MethodsIn this review, we have provided a summary of recommendations on the management of patients with cancer during the COVID-19 pandemic based on our experience in Shohada-e Tajrish Hospital, Iran.ResultsWe recommend that patients with cancer should be managed in an individualized manner during the COVID-19 pandemic.ConclusionsOur recommendation provides a guide for oncology centers of developing countries for better management of cancer.