Progression of radiotherapy for brain metastases in non-small cell lung cancer / 国际肿瘤学杂志

Brain metastases are one of the most common distant metastases in patients with non-small cell lung cancer (NSCLC), and the prognosis will be extremely poor. The effect of chemotherapy and operation is limited. As a standard treatment, radiotherapy is widely used in clinical practice. Radiotherapy alone includes whole brain radiotherapy, stereotactic radiotherapy and whole brain radiotherapy combined with stereotactic radiotherapy. With the continuous development of radiotherapy and the progress of gene sequencing, radiotherapy has been combined with targeted drugs, anti-angiogenic drugs and immunodrugs in the treatment of NSCLC brain metastasis, which can improve the survival of patients with NSCLC brain metastasis.

Review of Development of Emerging Clinical Antitumor Therapeutics / 肿瘤防治研究

With the continuous progress of tumor treatment methods in recent years, more and more emerging antitumor drugs have been approved to market and put into clinical use. In addition, some treatments that are in clinical trials such as gene therapy are also continuously making new breakthroughs. In this review, we mainly give a brief introduction to the novel antineoplastic therapies that have been clinically used in recent years, as well as the ones with remarkable efficacy and are expected to be approved for marketing.

Actualización de medicamentos asociados a necrosis avascular de los maxilares: perspectiva y revisión de literatura / Update of medications associated with avascular necrosis of the jaws: a perspective and literature review

La osteonecrosis de los maxilares está definida como la exposición de hueso necrótico en la región maxilofacial al menos por ocho semanas en pacientes que están recibiendo medicamentos antirresortivos para el tratamiento del cáncer primario o metastásico hacia el hueso, osteoporosis o enfermedad de Paget, sin historia previa de radiación. Desde el año 2003, la terminología utilizada estaba en relación con los bifosfonatos, en la actualidad ha sido introducido el término osteonecrosis de los maxilares relacionada por medicamentos (OMAM). La cirugía oral (implantología o cirugía periapical) incrementa el riesgo de OMAM, así como los desbalances concomitantes de la salud oral (inflamación dental y formación de abscesos). Las estrategias conservadoras en el tratamiento varían desde el cuidado local conservador hasta la resección quirúrgica radical del hueso necrótico. En el presente artículo se expone un análisis sistemático retrospectivo de la literatura en páginas como PubMed, ScienceDirect y Springer, Cochrane Library. Con el objetivo de resaltar el aumento de la incidencia de OMAM a nivel mundial con el uso de antirresortivos y otros medicamentos asociados en su patogenia en el Hospital Regional «General Ignacio Zaragoza¼ del ISSSTE, UNAM, en la Ciudad de México (AU)

Osteonecrosis of the jaws is defined as the exposure of necrotic bone in the maxillofacial region for at least 8 weeks in patients receiving antiresorptive medications for the treatment of primary or metastatic cancer towards the bone, osteoporosis, or Paget's disease, without previous history of radiation. Since 2003, the terminology used was related to bisphosphonates, the term medication-related osteonecrosis of the jaws has now been introduced. Oral surgery (implantology or periapical surgery) increases the risk of avascular necrosis, as well as concomitant imbalances in oral health (dental inflammation and abscess formation). Conservative strategies in treatment vary from conservative local care to radical surgical resection of the necrotic bone. In this article, a systematic retrospective analysis of the literature is presented on pages such as PubMed, Science Direct and Springer, Cochrane Library. And in which the objective is to highlight the increase in the incidence of medication related osteonecrosis of the jaws worldwide with the use of antiresorptive, and other associated medications in its pathogenesis at the Hospital Regional «General Ignacio Zaragoza¼ ISSSTE, UNAM in Mexico City (AU)

The early evaluation of lowGdose CT perfusion imaging for the treatment efficacy of lung cancer with anrotinib hydrochloride / 实用放射学杂志

Objective To explore whether CT perfusion imaging (CTPI)parameters can early predict the curative effect of anlotinib hydrochloride and their predictive accuracy for the treatment in lung cancer patients.Methods 2 6 patients with advanced nonGsmall cell lung cancer (NSCLC)were treated with anlotinib hydrochloride and underwent CTPI scanning before chemotherapy,after the first and second treatment cycle respectively.The average values of perfusion value (PV),peak enhancement image (PEI),time to peak (TTP),blood volume (BV)and the change rate of these parameters after one treatment cycle every time were measured and recorded. According to the response evaluation criteria in solid tumors 1.1 (RECIST1.1),the maximum diameter of the target tumor was measured and the tumor regression rate after two treatment cycles was calculated.Then a correlation analysis was conducted between the change rate of perfusion parameters (PV%,PEI%,TTP%,BV%)after one treatment cycle and the tumor regression rate (D%)after two treatment cycles. The ROC curve was performed to evaluate the accuracy of those parameters.Results PV after one treatment cycle was significantly lower than that before treatment,and PV% showed a statistical difference (P＝0.00).The PV% after one treatment cycle was positively correlated with D% after two treatment cycles (r＝0.56).In addition,the AUC of PV% and BV% were 0.99 and 0.88 respectively, and specificity were both 100%,with sensitivity respectively 75.7% and 82.6%.Conclusion CTPI can early reflect the curative effect of anlotinib hydrochloride for advanced NSCLC and provide more options for clinical evaluation.

Pseudoxantoma elástico / Pseudoxanthoma elastic

Resumo O pseudoxantoma elástico é uma doença generalizada do tecido conjuntivo envolvendo a pele, olhos e sistema cardiovascular desencadeando a fragmentação e calcificação das fibras elásticas. Geralmente ocorre após a puberdade, as manifestações características são manchas pequenas, circunscritas, amareladas, localizadas no pescoço, axila e pregas inguinais. Estrias angioides na retina, tendência à hemorragia e insuficiência arterial são as complicações mais comuns. Esta doença pode ser herdada como autossômica dominante ou recessiva. O tratamento das manifestações oculares convencional é através da fototerapia a laser impedindo a ocorrência de hemorragias locais. Entretanto, novas abordagens terapêuticas estão sendo desenvolvidas como a utilização em longo prazo de drogas antiangiogênicas, as quais atuam inibindo a neovascularização ocular. Apesar de não ter ainda efetivamente substituído o tratamento original, pesquisas recentes já evidenciam benefícios da nova técnica. O objetivo deste estudo é relatar sobre o caso de uma paciente de 37 anos, portadora do pseudoxantoma elástico, com estrias angioides e hemorragia ocular, e o tratamento eficaz com a terapia antiangiogênica no ambulatório de oftalmologia em Nova Iguaçu, Rio de Janeiro.

Abstract The pseudoxanthoma elasticum is a generalized disease of the connective tissue involving the skin, eyes and cardiovascular system triggering the fragmentation and calcification of elastic fibers. Usually occurs after puberty, the manifestations characteristics are small spots, circumscribed, yellowish, located on the neck, axilla and inguinal folds. Angioid streaks in the retina, tendency to hemorrhage and arterial insufficiency are the most common complications. This disease can be inherited as autosomal dominant or recessive. The treatment of ocular manifestations is through the conventional phototherapy laser preventing the occurrence of local hemorrhages. However, new therapeutic approaches are being developed as the long-term use of drugs antiangiogenic, which act by inhibiting the ocular neovascularization. Despite not having yet effectively replaced the original treatment, recent research already show benefits of new technique. The objective of this study is to report on a case of a patient of 37 years, the carrier of the Pseudoxanthoma Elasticum, with angioid streaks and ocular hemorrhage, and the effective treatment with antiangiogenic therapy at the clinic of Ophthalmology in Nova Iguaçu, Rio de Janeiro.

Treatment options after sorafenib failure in patients with hepatocellular carcinoma

Second line therapy after failure of sorafenib continues to be under study. Prognosis of hepatocellular carcinoma is measured in months, with median overall survival reaching 10.7 months with sorafenib. Because of the modest net benefit sorafenib has contributed, and rising incidence of hepatocellular carcinoma in the world, continued efforts are ongoing to look for efficient upfront, second line, or combination therapies. Herein we review the most relevant to date published literature on treatment options beyond sorafenib, reported studies, ongoing investigational efforts, and possibilities for future studies in advanced hepatocellular carcinoma.

Antiangiogenic Therapy Impedes Infiltration by CD4+ and CD8+ Cells Into an Early Colon Tumor

BACKGROUND: While the majority of angiogenesis studies have focused on the late stages of cancer, the emergence of neovascularization in colon tumorigenesis has been observed an earlier stage than expected. Recent reports implied that early angiogenesis might be a defense mechanism to stimulate the natural clearance of microadenomas during colon tumorigenesis. However, little is known about how early angiogenesis affects the natural clearance of tumors. METHODS: Spontaneous colon tumors were developed in adenomatous polyposis coli conditional knockout mice with Cre recombinase adenovirus administration. Vascular endothelial growth factor (VEGF) antagonist, DC101, was administrated to determine the effect of early angiogenesis and then infiltration of immune cells into tumor and concentration of cytokines were evaluated. RESULTS: The continuous administration of the VEGF receptor 2 antagonist DC101 in the mouse models impeded the infiltration by CD4+ and CD8+ cells into the tumor region. Furthermore, the administration of the VEGF antagonist decreased the amounts of anti-tumoral cytokines such as interleukin (IL)-6 and IL-10. CONCLUSIONS: We revealed that newly formed vessels during tumorigenesis can be channels for particular anti-tumoral immune cells. Our results may confer insight for the clinical development of an efficient antiangiogenic therapeutic manual and a timely chemoprevention to suppress tumor growth.

Present Status and Problems on Molecular Targeted Therapy of Cancer / Journal of the Korean Cancer Association, 대한암학회지

Numerous clinical trials of molecular targeted drugs for cancer have been conducted, with remarkable results for certain drugs and accumulation of "negative data" causing a hitch in the development plan for some other compounds. Five recent issues and problems of molecular targeted therapies were discussed critically. Drug discovery and effects against driver mutations (activating mutations) and problems: possibility for circumventing inherent and acquired resistance with the aim of achieving radical cure. Synthetic lethality: reasonable patient selection in individualized treatment strategy. Response rate and progression-free survival improvement with or without overall survival benefit and enhancement of toxicity in bevacizumab therapy: best endpoints for the evaluation of effect of antiangiogenic therapy. Negative data on small-molecule targeted therapy, primarily vascular endothelial growth factor tyrosine kinase inhibitors: loose GO or NO-GO decision criteria for further development of new compounds in early clinical trials. Effect of immunotherapy: difficulty to verify by proof of principle study. We are faced to many questions for the development of efficient personalized therapy. Accumulation of scientific global preclinical and clinical evidences is essential to use these new therapeutic modalities for the improvement of oncologic health care.

Improving Conventional or Low Dose Metronomic Chemotherapy with Targeted Antiangiogenic Drugs / Journal of the Korean Cancer Association, 대한암학회지

One of the most significant developments in medical oncology practice has been the approval of various antiangiogenic drugs for the treatment of a number of different malignancies. These drugs include bevacizumab (Avastin(R)), the anti-VEGF monoclonal antibody. Thus far, bevacizumab appears to induce clinical benefit in patients who have advanced metastatic disease only or primarily when it is combined with conventional chemotherapy. The reasons for the chemo-enhancing effects of bevacizumab are unknown, and this is a subject that we have been actively studying along with additional ways that antiangiogenic drugs may be combined with chemotherapy. In this respect, we have focused much of our effort on metronomic low dose chemotherapy. We have been studying the hypothesis that some chemotherapy drugs at maximum tolerated doses or other cytotoxic-like drugs such as acute "vascular disrupting agents" (VDAs) can cause an acute mobilization of proangiogenic cells from the bone marrow which home to and colonize the treated tumors, thus accelerating their recovery. These cells include endothelial progenitor cells. This systemic process can be largely blocked by a targeted antiangiogenic drug, e.g. anti-VEGFR-2 antibodies. In addition, metronomic chemotherapy, i.e., close regular administration of chemotherapy drugs at low non-toxic doses with no breaks, over prolonged periods of time not only prevents the acute CEP bone marrow response, but can even target the cells. This potential antiangiogenic effect of metronomic chemotherapy can also be boosted by combination with a targeted antiangiogenic agent. Treatment combinations of metronomic chemotherapy and an antiangiogenic drug have moved into phase II clinical trial testing with particularly encouraging results thus far reported in metastatic breast and recurrent ovarian cancer. Oral chemotherapy drugs such as cyclophosphamide (CTX), methotrexate are the main chemotherapeutics used for such trials. Oral 5-FU prodrugs such as UFT would also appear to be highly suitable based on long term adjuvant therapy studies in patients. Recent preclinical results using metronomic cyclophosphamide and metronomic UFT in models of advanced metastatic breast cancer suggest that this type of combination might be particularly promising for metronomic chemotherapy in this indication, particularly when combined with a targeted antiangiogenic drug.

The effect of anti-VEGF antiserum on the progression of bladder cancer in mouse model / 中华泌尿外科杂志

Objective To investigate the effect of antiserum against VEGF on angiogenesis and growth of bladder cancer in a mouse model in order to explore a novel strategy for the treatment of bladder cancer. Methods Antiserum against VEGF was prepared by using recombinant human VEGF and was identified for its specific affinity with VEGF by ELISA.The bladder carcinoma cell lines BST739 were implanted in T739 mice which were randomly divided into 2 groups:the control group receiving normal mice serum intraperitoneally,and the experimental group receiving antiserum against VEGF intraperitoneally.All the animals were sacrificed at last.Then all the bladder carcinomas were weighted and the microvessel density (MVD) in them was studied by immunohistochemical staining. Results The antiserum against VEGF was prepared and demonstrated with high specificity. The MVD in the antiserum group was lower than that in the control group. But the average weight of tumors was not significantly less in the antiserum group. Conclusions The study shows that to inhibit the activity of VEGF may reduce the angiogenesis in bladder cancer and supports the antiangiogenic therapy for bladder cancer.Inhibition of VEGF activity might become an important way of adjuvant therapy for bladder cancer.

Inhibitory effects of angiostatin gene combined with antisense hypoxia inducible factor-1? gene transfection on implanted human ovarian carcinoma in nude mice / 中国肿瘤生物治疗杂志

Objective: To observe the synergistic inhibitory effect of angiostatin gene combined with antisense hypoxia inducible factor-1? (aHIF-1?) gene on implanted human ovarian carcinoma in nude mice. Methods: BALB/C nude mice were subcutaneously transplanted with SKOV3 tumor cells and the tumors were allowed to grow till the diameter reached 0.4 cm, then the mice were randomly divided into 4 groups: PcDNA3 control group, PcDNA3-Angiostatin group, PcDNA3B-aHIF-1? group and PcDNA3-Angiostatin+PcDNA3B-aHIF-1? group; plamids PcDNA3, PcDNA3-Angiostatin, PcDNA3B-aHIF-1? and PcDNA3-Angiostatin+PcDNA3B-aHIF-1? were injected intra-tumorally in the above groups, respectively. The tumor samples were harvested on the 7 th day after gene transfer. Angiostatin, HIF-1?, vascular endothelial growth factor (VEGF) and microvessel density (MVD) of tumors were determined by immunohistochemical methods. Tumor cell apoptosis was determined with TUNEL staining. Results:The growth of tumors of PcDNA3-Angiostatin+PcDNA3B-aHIF-1? group was significantly inhibited, with local low expression of HIF-1? and VEGF (lower than those of the other 3 groups). MVD in combined transfection group(13.6?2.3) was lower than that of Angiostain group (24.5?2.7); the apoptosis index in combined transfection group (5.32?0.62)was higher than those of Angiostatin group(2.89?0.45), aHIF-1? group(2.98?0.51)and contrl group(1.56?0.41). Conclusion: Our results suggest a synergestic effect between Angiostain gene and aHIF-1? gene in inhibiting implanted human ovarian tumors in nude mice, which may contribute to drug resistance in antiangiogenic therapy of tumors.

Inhibitory effect of adenovirus mediated VEGF-siRNA on transplanted osteosarcoma in nude mice / 中国肿瘤生物治疗杂志

Objective: To investigate the inhibitory effect of adenovirus-mediated VEGF-siRNA on transplanted osteo- sarcoma in nude mice.Methods: VEGF-siRNA gene was cloned into the genome of replication-deficient adenovirus to construct Ad-VEGF-siRNA;the latter was then used to infect osteosarcoma MG63 cell line in vitro;and the expression of VEGF gene was detected by RT-PCR.Osteosarcoma transplantation model was established in nude mice;VEGF expression in tumor tissue was analyzed and the inhibitory effect on tumor growth and lung metastasis were also observed.Results: The recombinant adenovirus vector Ad-VEGF-siRNA was successfully constructed.In vivo and in vitro experiment both showed that Ad-VEGF-siRNA significantly downregulated VEGF expression in MG63 cells and transplanted tumor tissue. It was found that Ad-VEGF-siRNA significantly inhibited transplanted osteosarcoma growth(P