吉西他滨联合卡培他滨治疗蒽环类和紫杉类耐药的转移性乳腺癌

目的:观察吉西他滨(Gemcitabine)联合卡培他滨(Capecitabine)治疗蒽环类和紫杉类药物耐药的转移性乳腺癌患者的近期疗效和不良反应。方法:40例患者采用吉西他滨联合卡培他滨方案化疗:吉西他滨1000mg/m2静脉滴注,第1、8天;卡培他滨1000mg/m2口服,每日两次,第1-14天;21天为1周期。每2周期评价疗效,每周期进行毒性和安全性评估。结果:40例患者共接受156周期化疗,中位化疗周期4个(2-6个周期),总有效率(overall remission rate,RR)为35.00%(14/40),其中临床完全缓解率(clinical completeremission,cCR)为7.50%(3/40),部分缓解率(partial remission,PR)为27.50%(11/40),稳定率(stable dis-ease,SD)为30.00%(12/40),进展率(progressive disease,PD)为35.00%(14/40)。结论:吉西他滨联合卡培他滨是治疗蒽环类和紫杉类药物耐药的转移性乳腺癌的有效方案,其血液学和非血液学毒性耐受性良好。     

Methylene chloride fraction of the leaves of Thuja orientalis inhibits in vitro inflammatory biomarkers by blocking NF-κB and p38 MAPK signaling and protects mice from lethal endotoxemia

Aim of the study

Thuja orientalis (TO) has been a recognized herbal medicine across Northeast Asian countries for thousands of years and used for the treatment of various inflammatory diseases through as yet undefined mechanisms. In this study, we set out to determine whether the anti-inflammatory effects of this plant are mediated to suppress mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) activation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells.

Materials and methods

RAW 264.7 cells were pretreated with the methylene chloride fraction of TO (MTO) and stimulated with LPS. Nitric oxide (NO) release was determined by the accumulation of nitrite in the culture supernatants and tumor necrosis factor-α (TNF-α) and IL-6 secretion were determined by immunoenzymatic assay. Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression were evaluated via RT-PCR and Western blotting. NF-κB activation was also evaluated by reporter gene assay and electrophoretic mobility shift assay (EMSA). In addition, the protective effect of MTO was evaluated by use of the LPS-induced endotoxin shock model in mice.

Results

We found that MTO significantly suppressed LPS-stimulated NO and IL-6 production without affecting cell viability. MTO inhibited the expression of LPS-induced iNOS and COX-2 protein and their mRNA expression. Also, TNF-α and IL-6 secretion were decreased by MTO in both PMA and ionomycin-stimulated splenocytes. As a result, MTO inhibited pro-inflammatory cytokines such as TNF-α and IL-6, which is hypothesized as being due to the suppression of LPS-induced p38 MAPK and NF-κB activation. Moreover, MTO improved the survival rate during lethal endotoxemia by inhibiting the production of TNF-α in an animal model and our LC-MS analysis showed that a major component of MTO was pinusolide.

Conclusions

We demonstrate here the evidence that the methylene chloride fraction of Thuja orientalis (MTO) potentially inhibits the biomarkers related to inflammation in vitro and in vivo, and might be provided as a potential candidate for the treatment of inflammatory diseases.     

AMP-activated protein kinase modulators: a patent review (2006 - 2010)

INTRODUCTION: AMPK is a key player in the regulation of energy balance at both the cellular and whole-body levels, placing it at the center stage in studies of metabolic disorders. Recently, AMPK has also been identified as a potential target for either therapy or prevention of some types of cancer. Thus, identification of AMPK modulators for possible use as novel therapeutic drugs, both for treatment of metabolic disorders and cancer, will have a high commercial potential. AREAS COVERED: This review covers the structures and activities of AMPK modulators described in the patent literature since 2006. The patents reviewed include those for direct and/or indirect activators of AMPK, and novel pharmaceutical compounds with potential for use in the prevention and/or treatment of metabolic disorders, and cancer targeting AMPK. EXPERT OPINION: Targeting of AMPK appears to be an attractive strategy in the treatment of metabolic disorders. However, some detrimental effects of AMPK have also been reported, including a possible tumor-promoting effect in some settings and a heart disease-causing effect. Moreover, activation of AMPK in the hypothalamus may cause undesired consequences, such as an increase in feeding and body weight gain. These effects, therefore, must be carefully assessed for the development of therapeutic drugs targeting AMPK.     

Protective effects of Mentha haplocalyx ethanol extract (MH) in a mouse model of allergic asthma

Mentha haplocalyx Briq., a commonly used herb in traditional Oriental medicine, has a variety of known pharmacological properties. However, neither the protective effects of Mentha haplocalyx ethanol extract (MH) against inflammation of the airway in an asthmatic model nor the mechanisms involved, have previously been reported. In the present study, an ovalbumin (OVA)-induced mouse model of allergic asthma was used to investigate whether MH was effective against the disease through regulation of airway inflammation. The MH treatment significantly inhibited increases in immunoglobulin (Ig) E and T-helper 2 (Th2)-type cytokines such as IL-4 and IL-5 in bronchoalveolar lavage fluid (BALF) and lung tissue. Inflammatory cell infiltration of the airway in mice treated with MH was effectively alleviated when compared with infiltration seen in the OVA-induced group. These data indicated that decreased cytokine levels are the result of the decreased number of invaded leukocytes. Also, the generation of reactive oxygen species (ROS) in BALF was diminished by MH treatment. Taken together, these findings indicate that the administration of MH may have potential therapeutic value in the treatment of inflammatory disease.     

Testing for human papillomavirus in cervical cancer screening: a review of indications and methodology

High‐risk human papillomavirus (hrHPV) testing has become an integral component of cervical cancer screening, given that persistent infection with hrHPV was recognized as a significant risk factor for most precancers and cancers of the cervix. Particularly, testing for hrHPV types (in conjunction with cervical cytology) has been approved for primary screening in women over 30 years of age and for cost‐effective triaging of equivocal cervical cytology results. HPV was a small double‐stranded DNA virus that cannot be cultured in vitro; so, different types of tests have been developed to detect its presence. Various molecular techniques were available for detecting the presence and/or quantity of hrHPV. In this review, the testing options for hrHPV and its surrogates, with an emphasis on those approved by the US Food and Drug Administration (FDA), were detailed. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.