The Expression of Estrogen Receptor Subtypes in Prolactinomas and Their Relationship to Tumor Biological Behavior

Dopamine agonists （DA） are a first-line therapy for prolactinomas （PA）. However, nearly 10% of prolactinomas do not respond to DA therapy. A considerable number of studies have shown that estrogen plays an important role in the development of prolactinomas. However, the expression of estrogen receptors （ER） in prolactinomas has not been fully explored. Accordingly, we examined the levels of ESR1 and its subtypes A5-DeI-ESR1 and ESR2 mRNA in prolactinomas. In the present study,

Monitoring of Biological Responses of Tumor Cells after Irradiation with ^(99m)Tc-MIBI——An In Vitro Study

To explore the possibility to employ 99m Tc MIBI to monitor biological response of tumor cells after irradiation and to observe the relation between the radiation doses and the uptake levels of 99m Tc MIBI in tumor cells, the cells were irradiated with a single dose of 2 Gy, 10 Gy and 20 Gy respectively. The uptake of 99m Tc MIBI in each dosage group was determined before and 24, 48, 72 h after irradiation respectively. Apoptosis index , plating efficiency of tumor cells was simultaneously determined. There was a positive correlation between uptake levels of 99m Tc MIBI and AI. A negative correlation was noted between the uptake levels and PE . It is suggested that 99m Tc MIBI may be used as a tracer to monitor the change of viability state of tumor cells after being irradiated with different doses.

Spinal cord biological safety of image-guided radiation therapy versus conventional radiation therapy

Tumor models were simulated in purebred Beagles at the T9-10 levels of the spinal cord and treated with spinal image-guided radiation therapy or conventional radiation therapy with 50 or 70 Gy total radiation. Three months after radiation, neuronal injury at the T9-10 levels was observed, including reversible injury induced by spinal image-guided radiation therapy and apoptosis induced by conventional radiation therapy. The number of apoptotic cells and expression of the proapoptotic protein Fas were significantly reduced, but expression of the anti-apoptotic protein heat shock protein 70 was significantly increased after image-guided radiation therapy compared with the conventional method of the same radiation dose. Moreover, the spinal cord cell apoptotic index positively correlated with the ratio of Fas/heat shock protein 70. These findings indicate that 3 months of radiation therapy can induce a late response in the spinal cord to radiation therapy; image-guided radiation therapy is safer and results in less neuronal injury compared with conventional radiation therapy.

Evaluation of treatment response for breast cancer:are we entering the era of "biological complete remission"?

Breast cancer is one of the most common malignancies in women. The post-operative recurrence and metastasis are the leading causes of breast cancer-related mortality. In this study, we tried to explore the role of circulating tumor cell （CTC） detection combination PET/CT technology evaluating the prognosis and treatment response of patients with breast cancer; meanwhile, we attempted to assess the concept of ＂biological complete remission＂ （bCR） in this regard. A 56-year-old patient with breast cancer （T2N1M1, stage IV left breast cancer, with metastasis to axillary lymph nodes and lungs） received 6 cycles of salvage treatment with albumin-bound paditaxd plus eapecitaabine and trastuzumah. Then, she underwent CTC detection and PET/CT for efficacy evaluation. CTC detection combination PET/CT is useful for the evaluation of the biological efficacy of therapies for breast cancer. The bCR of the patient appeared earlier than the conventional clinical imaging complete remission and promised the histological （pathological） complete remission. The integrated application of the concepts including bCR, imageological CR, and histological CR can achieve the early and prognosis of breast cancer. accurate assessment of biological therapeutic reponse and

Hepatoma cell line HepG2.2.15 demonstrates distinct biological features compared with parental HepG2

AIM:To investigate the biological features of hepatitis B virus(HBV)-transfected HepG2.2.15 cells. METHODS:The cell ultrastructure,cell cycle and apoptosis,and the abilities of proliferation and invasion of HBV-transfected HepG2.2.15 and the parent HepG2 cells were examined by electron microscopy,flow cytometry, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and trans-well assay.Oncogenicity of the two cell lines was compared via subcutaneous injection and orthotopic injection or implantation in nude mice,and the pathological analysis of tumor formation was performed.Two cytoskeletal proteins were detected by Western blotting. RESULTS:Compared with HepG2 cells,HepG2.2.15 cells showed organelle degeneration and filopodia disappearance under electron microscope.HepG2.2.15 cells proliferated and migrated slowly in vitro,and hardly formed tumor and lung metastasis in nude mice.Flow cytometry showed that the majority of HepG2.2.15 cells were arrested in G1 phase,and apoptosis was minor in both cell lines.Furthermore,the levels of cytoskeletal proteins F-actin and Ezrin were decreased in HepG2.2.15 cells. CONCLUSION:HepG2.2.15 cells demonstrated a lower proliferation and invasion ability than the HepG2 cells due to HBV transfection.

Risk of infections associated with biological treatment in inflammatory bowel disease

Tumor necrosis factor-α (TNF-α) inhibitors are biological agents introduced in the late 1990s for the treatment of different immune-mediated diseases as inflammatory bowel disease, rheumatoid arthritis and psoriasis. The most commonly used TNF-α antagonists are infliximab, adalimumab, and certolizumab pegol, and though highly effective in lowering inflammation, the efficacy must be weighed against the potential for adverse events. The treatment-induced immunosuppression is suspected to increase the risk of infections, including the risk of reactivation of latent tuberculosis, as the TNF-α cytokine plays an important role in the immune function. In this topic highlight a short overview of the infection risk associated with TNF-α inhibiter therapy is outlined with a focus on the overall risk of serious infections, mycobacterial infection and latent viral infections.

Relationship between phenotypes of cell-function differentiation and pathobiological behavior of gastric carcinomas

AIM: To reveal the correlation between the functional differentiation phenotypes of gastric carcinoma cells and the invasion and metastasis by a new way of cell-function classification.METHODS:Surgically resected specimens of 361 gastric carcinomas(GC) were investigated with enzyme-, mucin-, and tumor-related marker immunohistochemistry. According to the direction of cell-function differentiation, stomach carcinomas were divided into five functionally differentiated types. RESULTS: (1) Absorptive function differentiation type (AFDT): there were 82 (22.7%) patients including 76 (92.7%) aged 45 years. Sixty-nine (84.1%) cases belonged to the intestinal type. Thirty-eight (46.3%) expressed CD44v6 and 9 (13.6%) of 66 male patients developed liver metastasis.The 5-year survival rate of patients in this group (58.5%) was higher than those with the other types (P【0.01). (2) Mucin secreting function differentiation type (MSFDT): 54 (15%) cases. Fifty-three (98.1%) tumors had penetrated the serosa, 12 (22.2%) expressed ER and 22 (40.7%) expressed CD44v6. The postoperative 5-year survival rate was 28.6%. (3) Absorptive and mucin-producing function differentiation type (AMPFDT): there were 180 (49.9%) cases, including 31 (17.2%) aged younger than 45 years. The tumor was more common in women (62, 34.4%,) and expressed more frequently estrogen receptors (ER) (129, 81.7%) than other types (P【0.01). Ovary metastasis was found in 12 (19.4%) out of 62 female subjects. The patients with this type GC had the lowest 5-year survival rate (24.7%) among all types. (4) Specific function differentiation type (SFDT): 13 (3.6%) cases. Nine (69.2%) tumors of this type derived from APUD system, the other 4 (30.7%) were of different histological differentiation. Sixty per cent of the patients survived at least five years. (5) Non-function differentiation type (NFDT): 32 (8.9%) cases. Nineteen (59.4%) cases had lymph node metastases but no one with liver or ovary metastasis. The 5-year survival rate was 28.1%. CONCLUSION: This new cell-function classification of GC is helpful in indicating the characteristics of invasion and metastasis of GC with different cell-function differentiation phenotypes. Further study is needed to disclose the correlation between the cell-functional differentiation phenotypes and the relevant genotypes and the biological behavior of gastric carcinoma.

Deterministic Parsing Model of the Compound Biological Effectiveness (<i>CBE</i>) Factor for Intracellular ¹⁰Boron Distribution in Boron Neutron Capture Therapy

Purpose: In defining the biological effects of the 10B(n, α)7Li neutron capture reaction, we have previously developed a deterministic parsing model to determine the Compound Biological Effectiveness (CBE) factor in Borono-Phenyl-Alanine (BPA)-mediated Boron Neutron Capture Therapy (BNCT). In present paper, we demonstrate that the CBE factor is directly and unambiguously derivable by the new formula for any case of intracellular 10Boron (10B) distribution, which is founded on this model for tissues and tumor. Method: To determine the CBE factor, we derive the following new calculation formula founded on the deterministic parsing model with three constants, CBE0, F, n and the eigen value Nth/Nmax. where, Nth and Nmax are the threshold value of boron concentration of N and saturation boron density in tissues and tumor. In order to determine these constants and the eigen values, iterative calculation technique was employed for the CEB factor and Nmax data set previously reported. Results and Conclusion: From the iterative calculation results, it is clear that the calculated CBE factor values obtained are almost identical to the original CBE factors and there is a good correlation between the original CBE factors and Nth/Nmax, when CBE0, F and n are given as 0.5, 8 and 3, respectively. These constants provide a better understanding of different types of intracellular10B distribution.

Determination of the Compound Biological Effectiveness (CBE) Factors Based on the <i>ISHIYAMA-IMAHORI</i>Deterministic Parsing Model with the Dynamic PET Technique

Purpose: In defining the biological effects of the 10B(n, α)7Li neutron capture reaction, we have proposed a deterministic parsing model (ISHIYAMA-IMAHORI model) to determine the Compound Biological Effectiveness (CBE) factor in Borono-Phenyl-Alanine (BPA)-mediated Boron Neutron Capture Therapy (BNCT). In present paper, we demonstrate a specific method of how the application of the case of application to actual patient data, which is founded on this model for tissues and tumor. Method: To determine the CBE factor, we derived the following new calculation formula founded on the deterministic parsing model with three constants, CBE0, F, n and the eigen value Nth/Nmax.? (1), where, Nth and Nmax are the threshold value of boron concentration of N and saturation boron density and CBE0, F and n are given as 0.5, 8 and 3, respectively. In order to determine Nth and Nmax in the formula, sigmoid logistic function was employed for 10B concentration data, Db(t) obtained by dynamic PET technique. (2), where, A, a and t0 are constants. Results and Conclusion: From the application of sigmoid function to dynamic PET data, it is concluded that the Nth and Nmax for tissue and tumor are identified with the parameter constants in the sigmoid function in Equation (2) as: (3). And the calculated CBE factor values obtained from Equation (1), with Nth/Nmax.

Post-operative abdominal complications in Crohn's disease in the biological era: Systematic review and meta-analysis

AIM: To perform a systematic review and meta-analysis on post-operative complications after surgery for Crohn's disease(CD) comparing biological with no therapy.METHODS: Pub Med, Medline and Embase databases were searched to identify studies comparing postoperative outcomes in CD patients receiving biological therapy and those who did not. A meta-analysis with a random-effects model was used to calculate pooled odds ratios(OR) and confidence intervals(CI) for each outcome measure of interest. RESULTS: A total of 14 studies were included for metaanalysis, comprising a total of 5425 patients with CD 1024(biological treatment, 4401 control group). After biological therapy there was an increased risk of total infectious complications(OR = 1.52; 95%CI: 1.14-2.03, 8 studies) and wound infection(OR = 1.73; 95%CI: 1.12-2.67; P = 0.01, 7 studies). There was no increased risk for other complications including anastomotic leak(OR = 1.19; 95%CI: 0.82-1.71; P = 0.26), abdominal sepsis(OR = 1.22; 95%CI: 0.87-1.72; P = 0.25) and re-operation(OR = 1.12; 95%CI: 0.81-1.54; P = 0.46) in patients receiving biological therapy. CONCLUSION: Pre-operative use of anti-TNF-α therapy may increase risk of post-operative infectious complications after surgery for CD and in particular wound related infections.

Advances in biological immunotherapy for gastric cancer:a mini-review

Gastric cancer immunotherapy refers to the use of biological technology to mobilize the immune function so that the body has a natural anti-cancer ability.It can be induced in vitro by collecting immune cells and cancer cells from patients with gastric cancer to form specific immune cell groups.Besides,a large number of these immune cell groups are cultured,separated,and then reinfused into patients,to achieve high efficiency,eliminate tumors and mobilize immune mechanisms in patients.In theory,this method can cure tumors because the principle of immunotherapy is to stimulate the body's autoimmune response.However,for some special populations,there may be more severe side effects.At present,the prediction,prevention,and treatment of this severe side effect are not complete.The immunotherapy of gastric cancer has not yet reached the full promotion,but it is a good treatment direction.It can be used clinically with chemotherapy and radiotherapy,surgery and traditional Chinese medicine cooperate,thereby achieving significant curative effects,and even curing gastric cancer.

Topical biological agents targeting cytokines for the treatment of dry eye disease

Because inflammation plays a key role in the pathogenesis of dry eye disease and Sjogren's syndrome, topical anti-inflammatory agents such as corticosteroids and cyclosporine A have been used to treat inflammation of the ocular surface and lacrimal gland. Systemic biological agents that target specific immune molecules or cells such as tumor necrosis factor(TNF)-α, interferone-α, interleukin(IL)-1, IL-6, or B cells have been used in an attempt to treat Sjogren's syndrome. However, the efficacy of systemic biological agents, other than B-cell targeting agents, has not yet been confirmed in Sjogren's syndrome. Several studies have recently evaluated the efficacy of topical administration of biological agents targeting cytokines in the treatment of dry eye disease. Topical blockade of IL-1 by using IL-1 receptor antagonist could ameliorate clinical signs and inflammation of experimental dry eye. Using a mouse model of desiccating stress-induced dry eye, we have demonstrated that topical application of a TNF-α blocking agent, infliximab, could improve tear production and ocular surface irregularity, decrease inflammatory cytokines and Th-1 CD4+ cells on the ocular surface, and increase gobletcell density in the conjunctiva. Although controversy still remains, the use of topical biological agents targeting inflammatory cytokines may be a promising therapy for human dry eye disease.

Is non-biological treatment of rheumatoid arthritis as good as biologics?

The management of rheumatoid arthritis(RA) in the past three decades has undergone a paradigm shift from symptomatic relief to a "treat-to-target" approach. This has been possible through use of various conventional and biologic disease modifying anti-rheumatic drugs(DMARDs) which target disease pathogenesis at a molecular level. Cost and infection risk preclude regular use of biologics in resource-constrained settings. In therecent years, evidence has emerged that combination therapy with conventional DMARDs is not inferior to biologics in the management of RA and is a feasible cost-effective option.

自身免疫疾病应用肿瘤坏死因子-α抑制剂后并发结核病33例临床特征分析

目的探讨自身免疫疾病患者应用肿瘤坏死因子-α抑制剂后并发结核病的临床特点、治疗及预后。方法收集2019年1月至2023年3月期间广州市胸科医院收治的33例应用生物制剂(肿瘤坏死因子-α抑制剂)后并发结核病患者的临床资料,其中男性25例,女性8例,中位年龄32岁,回顾性分析其临床症状、实验室检查结果、影像学及气管镜特征、病理特点、治疗及转归进行综合分析。结果常见临床表现为咳嗽(26/33)、咳痰(23/33)、发热(17/33)。发病多见于肺结核(32/33)、支气管结核(15/33)、纵隔及肺门淋巴结结核(11/33)。结核菌双侧全肺播散(21/33),结核菌肺内组织(支气管、纵隔肺门淋巴结、胸膜)播散(19/33),肺外结核(18/33),肺结核伴肺内组织或肺外结核(26/33)。血CD4+T淋巴细胞检测正常(23/33),血IGRA检测阳性(27/33)。肺部影像学粟粒性结节(8/33)。淋巴结组织病理为不典型肉芽肿结节。抗结核治疗疗程8~32个月。死亡1例。结论自身免疫疾病应用肿瘤坏死因子-α抑制剂后并发结核病患者以双肺病灶多见,易播散到肺内组织及全身多个器官,免疫功能下降,多需延长治疗疗程,经综合治疗多预后良好。

Recombination Mutant Human Tumor Necrosis Factor Combined with Chemotherapy in the Treatment of Advanced Cancer

Objective: Past studies showed that tumor necrosis factor (TNF) assisted anti-tumor treatment and intensified the sensitivity of chemotherapy. However its clinical application has been curbed because of its low purity, high dosage, and strong toxicity. The objective of present study is to evaluate the therapeutic effects and adverse reactions of recombinant mutant human tumor necrosis factor (rmhTNF) combined with chemotherapy in patients with advanced malignant tumor. Methods: 105 patients with advanced malignant tumor were randomly divided into trial group, 69 patients, and control group, 36 patients. rmhTNF was injected intramuscularly to the trial group at a dose of 4×106 U/m2, from the 1st to 7th days, the 11th to 17th days combined with chemotherapy course. The chemotherapy plan was as follows: CAP for patients with the NSCLC; FAM for patients with gastric cancer; FC for patients with colorectal cancer. One treatment cycle lasted for 21 days and two cycles were scheduled. The control group was given only the same chemotherapy as the trial group. Results: In the trial group there was 1 CR case and 12 PR cases, and the response rate was 13/69 (18.84%); in the control group 1 PR case, the response rate 1/36 (2.78%). The response rate in the trial group was significantly higher than that in the control group (P=0.022). The response rate for NSCLC in the trial group was 8/17 (47.06%), and 1/6 (16.67%) in the control group. The response rates for gastric cancer and colorectal cancer in the trial groups also were higher than those in the control groups. After the treatment the KPS was 89.00±9.92 in the trial group, and 84.17±8.84 in the control group, with a significant difference between the two groups (P=0.028). The adverse reactions of rmhTNF injection included: pain in the injection area, chill, hardening and swelling and redness in the injection area, fever, ostealgia and myosalgia, and cold-like symptoms. All these adverse reactions were mild and bearable. Conclusion: The administration of rmhTNF in combination with general chemotherapy is an effective and secure means in treating advanced malignant tumor.

组蛋白乳酸化修饰在恶性肿瘤中的研究进展

组蛋白赖氨酸乳酸化修饰是2019年新发现的一种酰化修饰,在基因表达、细胞代谢以及疾病治疗等生物过程中发挥着重要作用。近年来,乳酸化修饰生化相关研究取得突破性进展,尤其是在乳酸化修饰的生理功能以及与疾病相关性等领域逐渐受到关注。本文简要介绍乳酸化修饰的鉴定、生物学功能及其在恶性肿瘤中的作用,这将为进一步探索乳酸化修饰的功能和机制提供理论基础。

Ga基液态金属在生物医学应用的研究进展

介绍了Ga基液态金属(GaLMs)的主要理化性质,这些性质为GaLMs应用奠定了基础。从诊断和治疗两方面总结了GaLMs在生物医学领域应用的进展,包括可穿戴柔性传感、生物成像、肿瘤治疗及其他疾病治疗。围绕GaLMs的结构优化、长期生物安全性及诊疗一体化等,讨论了GaLMs在生物医学应用中面临的挑战和未来的发展方向。

miR-93-5p/FOXJ2轴介导胃癌细胞的生物学功能

目的:评估miR-93-5p对胃癌细胞的调节和功能。方法:采用qPCR检测miR-93-5p在胃癌组织、胃癌细胞系中表达,MTT、克隆形成、Transwell实验检测miR-93-5p对胃癌细胞增殖、侵袭的影响,双荧光素酶报告基因实验检测miR-93-5p与FOXJ2的靶向关系。结果:miR-93-5p在胃癌细胞系和胃癌组织中表达升高,抑制miR-93-5p表达后胃癌细胞增殖和侵袭能力受抑。双荧光素酶报告基因检测显示,miR-93-5p mimic显著降低MKN28和MKN45细胞Wt-FOXJ2相对荧光素酶活性,FOXJ2为胃癌细胞中miR-93-5p的直接靶基因。结论:miR-93-5p靶向FOXJ2促进胃癌细胞的增殖和侵袭,miR-93-5p/FOXJ2轴可能是判断胃癌预后的生物标志物和治疗靶点。

重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗中毒性表皮坏死松解症的疗效及安全性

目的探讨重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR:Fc)治疗中毒性表皮坏死松解症(TEN)患者的临床疗效及安全性。方法回顾性选取2020年1月至2022年1月海南医学院第一附属医院TEN患者20例,均给予rhTNFR:Fc治疗。治疗21 d后,记录TEN患者临床疗效,比较治疗前与治疗后不同时段(治疗后7、14、21 d)的药疹面积和严重程度指数(DASI)评分[DASI评分平均值,50%DASI(DASI50)、75%DASI(DASI75)、90%DASI(DASI90)所占比例]、血清肿瘤坏死因子α(TNF-α)水平、体温下降时间、皮疹控制时间、住院时间及药物治疗的安全性。结果治疗21 d后,TEN患者中,显效18例(90.00%),有效2例(10.00%)。TEN患者治疗后7、14、21 d的DASI评分分别为(30.44±5.68)、(5.28±2.31)、(2.04±1.12)分,均明显低于治疗前[(52.34±7.45)分],差异均有统计学意义(P<0.05)。相较治疗前、治疗7 d、治疗14 d,治疗21 d后的DASI50(100.00%)、DASI75(100.00%)、DASI90(90.00%)的改善比率最高,差异均有统计学意义(P<0.05)。TEN患者治疗后7、14、21 d的血清TNF-α水平分别为(22.73±5.58)、(15.99±4.60)、(4.44±1.10)pg/mL,均低于治疗前[(33.63±17.36)pg/mL],差异均有统计学意义(P<0.05)。TEN患者体温下降时间为(2.49±0.81)d,皮疹控制时间为(5.19±1.90)d,住院时间为(11.92±4.20)d。治疗期间患者未出现终止治疗或失访,均未出现急性不良反应,随访期间病情未见复发,定期复查结果显示并无合并症、活动性肝炎与结核疾病等。结论rhTNFR:Fc作为治疗TEN疾病的药物其疗效随治疗时间延长而提高,可降低血清TNF-α水平与DASI评分,且安全性较高。

电化学发光法和直接化学发光法测定12项肿瘤标志物指标的相关性和一致性评价

目的:评估电化学发光法和直接化学发光法测定12项肿瘤标志物的相关性和一致性。方法:选取2023年3-8月首都医科大学附属北京天坛医院体检血清标本2426例,在12项肿瘤标志物中甲胎蛋白(AFP)446例、癌胚抗原(CEA)284例、糖类抗原72-4(CA72-4)289例、糖类抗原19-9(CA19-9)87例、糖类抗原125(CA125)205例、糖类抗原15-3(CA15-3)216例、总前列腺特异性抗原(TPSA)292例、游离前列腺特异性抗原(FPSA)292例、细胞角蛋白19片段(Cyfra21-1)84例、神经元特异性烯醇化酶(NSE)84例、鳞状细胞癌相关抗原(SCC)84例、胃泌素释放肽前体(PROGrp)63例。分别采用电化学发光法和直接化学发光法对12项肿瘤标志物指标进行检测,分析两种检测方法的相关性与及一致性。结果:Pearson和Spearman相关性分析显示,电化学发光和直接化学发光法检测肿瘤标志物的AFP、CEA、CA72-4、CA19-9、CA125、CA15-3、TPSA、FPSA、Cyfra21-1、NSE、SCC和PROGrp12项指标均具有显著正相关性(r=0.971、0.934、0.945、0.975、0.900、0.948、0.994、0.984、0.982、0.828、0.879、0.922,P<0.05);两种方法检测总符合率分别为98.21%、98.24%、98.27%、98.85%、97.07%、99.54%、99.66%、99.32%、92.86%、92.86%、95.24%和96.83%,除CA15-3和NSE因数据原因无法计算Kappa值外,其余均有一致性(Kappa=0.848、0.728、0.930、0.794、0.485、0.887、0.664、0.540、0.477、0.652,P<0.05)。结论:电化学发光法和直接化学发光法检测肿瘤标志物中AFP、CA72-4、CA19-9、TPSA相关性及一致性较好,CEA、CA125、FPSA、Cyfra21-1、SCC、PROGrp相关性较好,但一致性一般,CA15-3、NSE相关性较好。临床在参考实验室检测结果时应注意检测方法的不同可能存在着结果差异。