Biomechanical Characteristics of Idiopathic Pulmonary Fibrosis / 医用生物力学

Idiopathic pulmonary fibrosis (IPF) is a common chronic interstitial fibrotic disease. During the fibrosis process, myofibroblasts are abnormally activated, collagen is deposited in large quantities and the biomechanical characteristics of lung tissue are significantly altered. In this paper, a systematic review about the changes in lung tissues, cellular biomechanical properties and biomechanical signals during the process of IPF was presented, and the in vitro reproduction of biomechanical features and therapeutic strategies for targeting biomechanics wassummarized, so as to provide references for clinical prevention and treatment of IPF.

Small cell lung cancer: an overview of the targets

Abstract Lung cancer is the leading cause of cancer deaths worldwide. Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancer cases. Despite a frequently good response to first-line treatment with chemotherapy and/or radiotherapy, early relapse occurs in the majority of patients and 5-year survival is only about 5%. This histological subtype of lung cancer is strongly associated with tobacco smoking. The behavior of SCLC is unique within solid tumors. Initially, it positively responds to chemotherapy or radiotherapy. However, at relapse, which occurs early in the majority of cases, the tumor is resistant to available therapy and eventually will cause the death of the patient. These results in an overall 5-year survival of approximately 5% for the entire population of patients diagnosed with SCLC. This dismal prognosis has not significantly changed in past years. There is an urgent need for discovery targets to select patients more prone to having a proper response to the treatment, avoiding to reduce their resistance and resulting the increase of overall and progression-free survivals.

Treatment Sequencing Strategies in Lung Cancer / 中国肺癌杂志

BACKGROUND@#The advances in the lung cancer screening methods and therapeutics, together with awareness towards deleterious habits, such as smoking, is increasing the overall survival with better quality of life for the patients. However, lung cancer is still one of the most common and fatal neoplasm with a high incidence and consequently burden to public health worldwide. Thus, based on guidelines and recent phases II and III clinical trials studies, this manuscript summarizes the current treatment sequencing strategies in lung cancer.@*METHODS@#A comprehensive search of related articles was performed focused on phases II and III clinical trials studies.@*RESULTS@#The lung cancer management should take into consideration the tumor characteristics, histology, molecular pathology and be discussed in a multidisciplinary team. Lung cancer treatment options comprises surgery whenever possible, radiotherapy associate with/or chemotherapy and immunotherapy as monotherapy, or combined with chemotherapy and best palliative care.@*CONCLUSIONS@#The screening predictability in more patients, smoking reduction, early diagnosis, better disease understanding and individualized, more effective and tolerable therapeutics are related to an increasing in overall survival and quality of life. In the near future improvement of personalized therapy in precision medicine is expected, enhancing new predictive biomarkers, optimal doses and optimal treatment sequencing as well as anti-cancer vaccines development.

Research Advance in Treatment of Thrombotic Thrombocytopenic Purpura --Review / 中国实验血液学杂志

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy, in which a severe deficiency of von Willebrand factor lyase results in thrombocytopenic clots that block blood vessels and eventually lead to terminal organ failure. Therapeutic plasma exchange is the cornerstone of TTP treatment which can greatly improves the survival rate of the patients. With the further exploration to the pathophysiological mechanism of TTP, other alternative therapies, new immunosuppressive agents, targeted antagonists, gene therapy and other emerging means gradually emerge, which are expected to further reduce the mortality and recurrence rate of the patients. In this review, the new developments in TTP treatment were summarized briefly.

Terapias dirigidas a dianas moleculares: perspectiva actual en la leucemia promielocítica / Molecular targeted therapies: current perspectives in acute promyelocytic leukemia

Introducción: La leucemia promielocítica presenta particularidades biológicas y clínicas con respecto al resto de las leucemias mieloides agudas. El descubrimiento de los detalles moleculares de su patogénesis, posibilitó que su tratamiento, constituya una de las mejores representaciones de la investigación traslacional y esto hace que establezca un modelo para el desarrollo de terapias dirigidas a dianas moleculares con enfoque curativo en pacientes con cáncer. Objetivo: Abordar los principales avances en la terapia de la LPM desde el descubrimiento de los agentes diferenciadores hasta su estado actual. Métodos: Se realizó una búsqueda exhaustiva en bases de datos como Scielo, Pubmed, ScienceDirect, Redalyc y se utilizaron como referencias los artículos actualizados publicados principalmente en los últimos cinco años. Análisis y síntesis de la información: Se abordaron los principales avances en la terapia de este tipo de leucemia, desde el descubrimiento de los agentes diferenciadores hasta su estado actual, haciendo énfasis en su mecanismo de acción y nuevas opciones terapéuticas. Conclusiones: Los aportes realizados en el estudio etiopatogénico y molecular de la leucemia promielocítica y su impacto objetivo en la investigación clínica, constituyen uno de los mejores ejemplos de tratamiento dirigido a alteraciones moleculares específicas y representa un modelo de integración biológica, clínica y terapéutica en beneficio de los pacientes afectados con esta enfermedad(AU)

Introduction: Acute promyelocytic leukemia is a biologically and clinically different type from other acute myeloid leukemias. The discovery of molecular details in its pathogenesis enabled its treatment to constitute one of the best examples of translational research and makes a model for the development of targeted therapies with a curative approach in cancer patients. Objective: To analize the main advances in PML therapy from the discovery of differentiating agents to their current state. Methods: An exhaustive search was carried out in the databases as Scielo, Pubmed, ScienceDirect, Redalyc, and updated articles published mainly in the last five years were used as references. Analysis and synthesis of the information: The article addressed the main advances in the therapy of this type of leukemia, from the discovery of differentiating agents to its current state, emphasizing its mechanism of action and new therapeutic options. Conclusions: The contributions made in the etiopathogenic and molecular study of promyelocytic leukemia and its objective impact on clinical research constitute one of the best examples of treatment aimed at specific molecular alterations and represents a model of biological, clinical and therapeutic integration in benefit of patients affected with this disease(AU)

Genes involucrados en el cáncer pulmonar / Genes involved in lung cancer

Introducción: El cáncer pulmonar constituye un serio problema de salud mundial por su elevada prevalencia y mortalidad. En la carcinogénesis pulmonar están implicados oncogenes y genes supresores tumorales, que en una compleja interacción con factores ambientales favorecen la transformación cancerosa. Objetivo: Describir los principales genes implicados en el cáncer pulmonar. Métodos: Se buscaron referencias en las bases de datos PubMed Central, Annual Reviews y SciELO. Se revisaron preferentemente los artículos originales, las revisiones bibliográficas, las revisiones sistemáticas y los metaanálisis de los últimos cinco años. Análisis e integración de la información: En la carcinogénesis pulmonar se involucran los oncogenes JUN, FOS, ABL1, BRAF, RAF1, GNAS, KRAS, NRAS, HRAS, CSF 1R, MYC, EGFR, MET, ALK, CCNE1, DDR2, ERBB3, FGFR1, MDM2, ROS1, SOX2 y TP63 y los genes supresores tumorales TP53, CDKN2A, CDKN1A, RB1, CDK2AP1, ATM, ERCC2, BRCA1, CCND1, STK11, PDLIM2, PTEN, ARID1A, ASCL4, CUL3, EP300, KEAP1, KMT2D, NF1, NOTCH1, RASA1, ETD2 y SMARCA4. El conocimiento de la genética molecular del cáncer pulmonar es importante para la identificación de biomarcadores diagnósticos y pronósticos más eficaces y para el diseño de fármacos diana sobre genes específicos(AU)

Introduction: Lung cancer is a serious global health problem due to its high prevalence and mortality. Lung carcinogenesis involves oncogenes and tumor suppressor genes which interact in complex manners with environmental factors, paving the way for the cancerous transformation. Objective: Describe the main genes involved in lung cancer. Methods: References were searched for in the databases PubMed Central, Annual Reviews and SciELO. Particular attention was paid to original papers, bibliographic reviews, systematic reviews and meta-analyses published in the last five years. Data analysis and integration: Lung carcinogenesis involves the oncogenes JUN, FOS, ABL1, BRAF, RAF1, GNAS, KRAS, NRAS, HRAS, CSF 1R, MYC, EGFR, MET, ALK, CCNE1, DDR2, ERBB3, FGFR1, MDM2, ROS1, SOX2 and TP63, and the tumor suppressor genes TP53, CDKN2A, CDKN1A, RB1, CDK2AP1, ATM, ERCC2, BRCA1, CCND1, STK11, PDLIM2, PTEN, ARID1A, ASCL4, CUL3, EP300, KEAP1, KMT2D, NF1, NOTCH1, RASA1, ETD2 and SMARCA4. Knowledge about the molecular genetics of lung cancer is important to identify more efficient diagnostic and prognostic biomarkers and to design targeted drugs for specific genes(AU)

Experience in Using Jumihaidokuto and Orengedokuto for Skin Disorders Caused by Molecular Target Drugs / 日本東洋医学雑誌

In some molecular targeted therapies, skin disorders including acne-like rashes or maculopapular rashes frequently appear, which are often clinically problematic. In Kampo medicine, it has been reported that the combination of jumihaidokuto and orengedokuto (hereinafter called JHT + OGT) is effective for acne. In this study, we report the experiences of JHT + OGT for the treatment of rashes caused by molecular targeted therapies. We extracted patients from June 2013 to June 2017 who took molecular targeted therapies and the treatment with JHT + OGT for skin rashes. The primary endpoint was severity of rashes before and after treatment by JHT + OGT (judged by CTCAE v4.0). In 22 patients (14 males and 8 females), the rashes after treatment with JHT + OGT significantly improved compared with those before treatment (from the median grade of 2 to 1 [p = 0.011]), with 14 cases of improvement, 6 cases of no change, and 2 cases of deterioration. It was suggested that JHT + OGT for skin rashes caused by molecular targeted therapies could be one of the treatment options.

Research progress of vascular endothelial growth factor in bladder cancer / 医学研究生学报

Vascular endothelial growth factor (VEGF) is known as the most efficient promote blood vessel growth factor.Numerical novel researches has confirmed that it plays a key role in bladder cancer proliferation, invasion and metastasis. The increasing clinical trials have aimed at targeting VEGF pathway.The encouraging outcomes provide new feasibility on bladder tumor treatment. Theis review conducted to discuss the tumor promoting mechanisms, bladder cancer progression relevance and bladder tumor target therapy of VEGF.

Application of patient-derived tumor xenograft mouse models in guiding the clinical treatment / 中国肿瘤临床

Patient-derived tumor xenograft(PDTX)models are based on the transfer of primary tumor tissue directly from the patient into immunodeficient mice.PDTX models retain many of the key characteristics of the original cancers,including heterogeneity,histo-logical characteristics,molecular diversities,and host microenvironments.These models do not only serve as platforms for co-clinical trials to determine precisely targeted therapies,but can also be applied to the development of biomarkers and action targets for drug responsiveness and personalized drug selection.PDTX models combined with clinical,genomic,and pharmacodynamic data and ap-plied to the individualized treatment of cancer patients could increase the specificity of drug use,improve clinical treatment success, and promote the development of individualized treatment and precise medical regimes.This review summarizes the historical back-ground,influential modeling factors,clinical applications,and limitations of PDTX mouse models.

Novel Therapeutics for Recurrent or Metastatic Gastric Cancer / 대한내과학회지

Despite advances in cancer therapy, gastric cancer has a poor prognosis and high cancer-related mortality. Based on the molecular characteristics of cancer, specific targeted therapies have shown clinical benefits for various tumors. In addition, immunotherapy using immune checkpoint inhibitors has led to a paradigm shift in cancer treatment and shown remarkable results in some solid tumors. Although immunotherapy has been actively applied to gastric cancer, the efficacy is unsatisfactory compared with other solid tumors, such as melanoma and lung cancers. This is because of the complex mechanism of gastric cancer, tumor heterogeneity, heterogeneity among patients, and the absence of appropriate biomarkers to predict response. An effective new cancer treatment strategy that combines targeted therapies and various immunotherapies based on biological markers such as tumor mutation burden and microsatellite instability is urgently needed. Furthermore, customized treatment is necessary to overcome tumor heterogeneity.

Potential novel target drugs for anti-ovarian cancer targeted therapies:research advances / 国际药学研究杂志

Molecular target therapy plays an important role in the treatment of malignant tumor.But research and development progress is slow on drugs targeting ovarian cancer.Only bevacizumab and olaparib have been approved for treating ovarian cancer by the FDA or the EMA,and their clinical application is limited.In recent years,there have been more and more reports on molecular tar?get therapy of ovarian cancer.Research advances have been made on novel drugs targeting E3 ubiquitin ligase,VEGF/VEGFR signal?ing pathways,PD-1/PD-L1 signaling pathways,IL-6/IL-6R signaling pathways and macrophage migration-inhibitory factor.This arti?cle briefly summarizes the current progresses in studies of molecular target therapy in ovarian cancer.

Regulation of chromosome regulator EZH2 in cancer epigenetics and EZH2 targeted drugs in cancer therapy / 中国药理学与毒理学杂志

Enhancer of zeste homolog 2(EZH2)is the catalytic subunit of polycomb repressor complex 2(PRC2),a complex that methylates lysine-27 of histone H3(H3K27). PRC2 facilitates chro?matin compaction and gene silencing by modulating the methylation of H3K27,which is thought to be the classical function of EZH2 in several types of cancer. In some other situations,EZH2 also acts as an acti?vator of transcription in a PRC2-independent manner. EZH2 has been demonstrated to be extensively involved in the development and progression of cancer by inducing aberrant histone modification and gene transcription via aberrant EZH2 expression,functional mutation or other mechanisms which are very context-dependent. EZH2 inhibitors targeting the catalytic activity of EZH2 or the stability of PRC2 have been designed for cancer therapies and some of them have produced positive effects. This review focuses on the regulation of EZH2 on cancer epigenetics and the development of therapeutic drugs targeting EZH2.

Targeting the Phosphatidylinositol-3-kinase Pathway in Gastric Cancer: Can Omics Improve Outcomes? / 대한배뇨장애요실금학회지

Phosphatidylinositol-3-kinase (PI3K) pathway signaling is an established oncogenic signal transduction pathway implicated in multiple malignancies. Therapeutic targeting of PI3K pathway components has improved outcomes in chronic lymphocytic leukemia, kidney cancer, breast cancer, and neuroendocrine tumors. Gastric cancers harbor some of the highest rates of oncogenic alterations in PI3K but attempts to translate this genomic observation have met with limited clinical success and novel approaches are needed. In the following review we discuss PI3K signaling, previous preclinical and clinical investigations in gastric cancer, and discuss future strategies aimed at overcoming resistance and improving efficacy. Identification and refinement of molecular tumor subtypes, development of predictive biomarkers along, and rational drug combination strategies are key to capitalizing on the therapeutic potential of PI3K pathway directed therapies in gastric cancers.

Targeting the Phosphatidylinositol-3-kinase Pathway in Gastric Cancer: Can Omics Improve Outcomes? / 대한배뇨장애요실금학회지

Phosphatidylinositol-3-kinase (PI3K) pathway signaling is an established oncogenic signal transduction pathway implicated in multiple malignancies. Therapeutic targeting of PI3K pathway components has improved outcomes in chronic lymphocytic leukemia, kidney cancer, breast cancer, and neuroendocrine tumors. Gastric cancers harbor some of the highest rates of oncogenic alterations in PI3K but attempts to translate this genomic observation have met with limited clinical success and novel approaches are needed. In the following review we discuss PI3K signaling, previous preclinical and clinical investigations in gastric cancer, and discuss future strategies aimed at overcoming resistance and improving efficacy. Identification and refinement of molecular tumor subtypes, development of predictive biomarkers along, and rational drug combination strategies are key to capitalizing on the therapeutic potential of PI3K pathway directed therapies in gastric cancers.

Cure of human immunodeficiency virus/acquired immune deficiency syndrome: promising future prospects at horizon.

Acquired immune deficiency syndrome (AIDS) is a disease caused by human immunodeficiency virus and characterized by profound immunosuppression that leads to opportunistic infections, secondary neoplasms, and neurologic complications. AIDS is among the leading causes of death worldwide. Current therapeutic options are directed only toward management of AIDS, but not toward its prevention or cure. In addition, it also possesses numerous problems like drug resistance, drug toxicity, drug interactions, non-adherence to therapy, life-long and expensive treatment, etc. Recent years in drug development have shown promising prospects for prevention/ treatment/cure of AIDS like histone deacetylase inhibitors, Vpu ion channel inhibitors, viral decay acceleration, maturation inhibitors, tat antagonists, gene/stem cell therapy, and antiretroviral vaccines.

A new futuristic glaucoma therapeutic management paradigm.

Glaucoma is a group of diseases, characterized by a progressive form of optic nerve damage. Current studies indicate more selective pathophysiological involvement, thereby targeted therapies are warranted. Although both the prostaglandin analogs and beta blockers are still, most commonly used drugs for glaucoma, due to their effi cacy, lack of adverse effects. In addition, a stepped care approach is the corner stone for its management. In addition, attempts have been made to enhance patient compliance and ocular delivery of already available anti-glaucoma drugs such as pilocarpine and timolol maleate. Notable among futuristic treatment options are; novel delivery systems, benzalkonium chloride-free drugs, various glaucoma drainage devices, new targeted therapies and prompt diagnosis plus aggressive treatment, in patients with primary angle closure glaucoma. Promising new focus on vision sparing, greater patient safety and tolerability will provide improved treatment options and long-term preservation of vision and quality of life.

Molecular Pathogenesis and Targeted Therapies in Well-Differentiated Thyroid Carcinoma

Four proto-oncogenes commonly associated with well-differentiated thyroid carcinoma, rearranged during transfection (RET)/papillary thyroid cancer, BRAF, RAS, and PAX8/peroxisome proliferator activated receptor-gamma, may carry diagnostic and prognostic significance. These oncogenes can be used to improve the diagnosis and management of well-differentiated thyroid carcinoma. Limited therapeutic options are available for patients with metastatic well-differentiated thyroid cancer, necessitating the development of novel therapies. Vascular endothelial growth factor (VEGF)- and RET-directed therapies such as sorafenib, motesanib, and sunitinib have been shown to be the most effective at inducing clinical responses and stabilizing the disease process. Further clinical trials of these therapeutic agents may soon change the management of thyroid cancer.

Sunitinib in metastatic renal cell carcimoma: A single-center experience.

INTRODUCTION: Historically, metastatic renal cell carcinoma (RCC) has had poor prognosis; the outcomes have improved with the introduction of tyrosine‑kinase inhibitors, such as sunitinib. There is no reported literature from India on the use of sunitinib in metastatic RCC. We present an analysis of sunitinib at our institute over 4 years. MATERIALS AND METHODS: An unselected population of patients with metastatic or relapsed metastatic RCC receiving sunitinib was analyzed with respect to patient characteristics, response, toxicity, and outcomes. RESULTS: Fifty‑nine patients (51 males, 8 females) with a median age of 55 years were included in the study. Lungs and bones were the most common site of metastases. The patients received a median number of 4 cycles, with 23 patients requiring dose‑modification and 12 discontinuing therapy due to toxicity. Overall, 38 patients (65%) had CR, PR, or standard deviation while 14 had progression or death at initial evaluation. The median progression‑free survival (PFS) was 11.4 months and overall survival was 22.6 months. Hand–foot syndrome, fatigue, mucositis, skin rash, and vomiting were seen more often among our patients, whereas hypertension was not as common compared with previously published reports. CONCLUSION: Sunitinib is a viable option for the treatment of metastatic RCC and shows a comparable PFS in Indian patients. Although toxicity remains a concern, most of the adverse effects can be managed conservatively. Careful patient selection, tailoring the dose of therapy, adequate counseling, and careful follow‑up is essential for optimum therapy.

Prognostic factors of the invasion and metastasis of gastric cancer and their applications in targeted therapy / 国际外科学杂志

Invasion and metastasis are critical determinants on cancer morbidity.Genes and molecules participating in these steps have been demonstrated as potential prognostic factors.Growth factors and their receptors,cell-cycle regulators,cell-adhesion molecules and m trix-degrading enzymes are potentially used as prognostic factors.However,increased understandings for molecular mechanisms underlying carcinogenesis and its implementation in the treatment of gastric cancers have recently been focused on the development and incorporation of targeted agents with chemotherapy.

Targeted molecular therapies in thyroid carcinoma: [review] / Terapias moleculares direcionadas em câncer de tireoide: [revisão]

Thyroid cancer incidence has significantly increased in the last three decades and many patients seek medical attention for its treatment every year. Among follicular cell-derived tumors, the majority are differentiated thyroid carcinomas (DTC), whose prognosis is very good with only 15 percent of the cases presenting disease persistence or recurrence after initial treatment. Medullary thyroid carcinoma has a worse prognosis, especially in patients with diffused cancers at the time of initial surgery. Traditional treatment options for persistent or recurrent disease include additional surgery, radioiodine treatment and TSH-suppression in DTC patients; external beam radiotherapy, and cytotoxic chemotherapy, often have low efficacy and many patients with advanced disease ultimately die. In the last two decades many of the molecular events involved in cancer formation have been uncovered. This knowledge has prompted the development of novel therapeutic strategies mainly based on the inhibition of key molecular mediators of the tumorigenic process. In particular the class of small-molecule tyrosine kinase inhibitors was enriched by many compounds that have reached clinical trials and in some cases have had approval for clinical use in specific cancers. Many of these compounds entered clinical trials also for locally advanced or metastatic thyroid carcinomas showing very promising results.

O câncer de tireoide tem aumentado significativamente nas últimas três décadas e muitos pacientes têm buscado cuidados médicos para o tratamento a cada ano. Entre os tumores derivados de células foliculares, a maioria é carcinoma diferenciado de tireoide (CDT), cujo prognóstico é muito bom, em que somente em 15 por cento dos casos a doença é persistente ou recorrente após o tratamento inicial. O carcinoma medular de tireoide tem um prognóstico pior, especialmente em pacientes com câncer difuso no momento da cirurgia inicial. As opções no tratamento tradicional para a doença persistente ou recorrente incluem cirurgia adicional, radioiodoterapia e supressão de TSH em pacientes CDT; a radioterapia externa e a quimioterapia citotóxica apresentam com frequência uma baixa eficácia e muitos pacientes com doença avançada não sobrevivem. Nas últimas duas décadas, muitos dos eventos envolvidos na formação do câncer tornaram-se conhecidos. Esse conhecimento possibilitou o desenvolvimento de novas estratégias terapêuticas, baseadas principalmente na inibição de mediador molecularchave no processo tumorigênico. Em particular, a classe das pequenas moléculas inibidoras de tirosina-quinase foi enriquecida por muitos compostos investigados em estudos clínicos e alguns casos foram aprovados para uso clínico em tipos específicos de câncer. Muitos desses compostos foram aplicados em estudos clínicos de câncer de tireoide com extensa invasão local ou metástase, mostrando resultados muito promissores.