Molecular and cellular pharmacology最新文献

{"title":"Radiation resistance of cancer stem cells as an obstacle in cancer therapy","authors":"S. Chumsri, P. Shah","doi":"10.4255/MCPHARMACOL.13.06","DOIUrl":"https://doi.org/10.4255/MCPHARMACOL.13.06","url":null,"abstract":"Sh Faisal 14.00 Radiation represents an important therapeutic intervention in many tumor types. Nevertheless, tumor recurrence continues to post major limitation to this type of therapy. Wealth of data suggests that there is a distinct population of cancer cells with exclusive ability to self-renew, termed cancer stem cells (CSCs). This subset of cancer cells has been shown to be resistant to conventional therapy, including chemotherapy and radiation. Failure to eradicate CSCs may result in tumor recurrence. This review article summarized the characteristic and identification of CSCs along with mechanisms of resistance in these cells including increased DNA repair. Understanding the mechanisms underlying radioresistance of CSCs will lead to better combination therapies to overcome resistance of these cells which will ultimately improve outcome for radiation treatment. Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ \u0000 table.MsoNormalTable \u0000 {mso-style-name:\"Table Normal\"; \u0000 mso-tstyle-rowband-size:0; \u0000 mso-tstyle-colband-size:0; \u0000 mso-style-noshow:yes; \u0000 mso-style-priority:99; \u0000 mso-style-parent:\"\"; \u0000 mso-padding-alt:0in 5.4pt 0in 5.4pt; \u0000 mso-para-margin:0in; \u0000 mso-para-margin-bottom:.0001pt; \u0000 mso-pagination:widow-orphan; \u0000 font-size:12.0pt; \u0000 font-family:\"Calibri\",\"sans-serif\"; \u0000 mso-ascii-font-family:Calibri; \u0000 mso-ascii-theme-font:minor-latin; \u0000 mso-hansi-font-family:Calibri; \u0000 mso-hansi-theme-font:minor-latin;}","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"1 1","pages":"39-49"},"PeriodicalIF":0.0,"publicationDate":"2013-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78029860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic Stress and Disorders Related to Alterations in Mitochondrial Fission or Fusion.","authors":"Mansi Babbar,&nbsp;M Saeed Sheikh","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Mitochondrial morphology and metabolism play an important role in cellular homeostasis. Recent studies have shown that the fidelity of mitochondrial morphology is important in maintaining mitochondrial shape, number, size, membrane potential, ATP synthesis, mtDNA, motility, signaling, quality control, response to cellular stress, mitophagy and apoptosis. This article provides an overview of the current state of knowledge of the fission and fusion machinery with a focus on the mechanisms underlying the regulation of the mitochondrial morphology and cellular energy state. Several lines of evidence indicate that dysregulation of mitochondrial fission or fusion is associated with mitochondrial dysfunction, which in turn impacts mitophagy and apoptosis. Metabolic disorders are also associated with dysregulation of fission or fusion and the available lines of evidence point to a bidirectional interplay between the mitochondrial fission or fusion reactions and bioenergetics. Clearly, more in-depth studies are needed to fully elucidate the mechanisms that control mitochondrial fission and fusion. It is envisioned that the outcome of such studies will improve the understanding of the molecular basis of related metabolic disorders and also facilitate the development of better therapeutics.</p>","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"5 3","pages":"109-133"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921894/pdf/nihms-553422.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32123569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stereotactic Ablative Radiotherapy (SABR): Impact on the Immune System and Potential for Future Therapeutic Modulation.","authors":"Adam S Reese,&nbsp;Steven J Feigenberg,&nbsp;Azmat Husain,&nbsp;Tonya J Webb,&nbsp;Petr F Hausner,&nbsp;Martin J Edelman,&nbsp;Josephine Feliciano,&nbsp;Katherine H Tkaczuk,&nbsp;Navesh K Sharma","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Stereotactic ablative radiotherapy (SABR) has been demonstrated to provide excellent local control in several malignancies. Recent reports have suggested that this ablative dose may impact disease outside of the radiated area. Furthermore, these studies have implicated immune modulation as the primary mechanism of disease response outside the irradiated area. More specifically, T-cell stimulation and tumor necrosis factor-α modulation following high dose irradiation have been suggested as the responsible components of this phenomenon. In addition, the \"abscopal effect\" may play a role in disease response outside of the radiated area. We review the current literature regarding the effects of ablative radiation therapy, the potential for immune modulation from it, and the mechanisms of the distant effects it elicits.</p>","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"5 1","pages":"19-25"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4128167/pdf/nihms610625.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32587862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Roles of Radiotherapy and Immunotherapy for the Treatment of Lymphoma.","authors":"Amy S Kimball,&nbsp;Tonya J Webb","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Lymphoma is rising in incidence and there is a continued need for new and novel therapeutic options. Lymphomas are extremely radiosensitive, but the majority of patients are not candidates for involved field radiation therapy. An intact immune system has a critical role in suppressing lymphomagenesis. Here we discuss the contribution of various components of the immune system in suppressing the development of lymphoma, as elucidated from mouse models. We review the nature of the immune response to lymphoma in non-immunocompromised patients. Finally, we discuss the potential role of immunomodulation, in concert with radiation therapy, as a component of future therapeutic strategies for lymphoma.</p>","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"5 1","pages":"27-38"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955882/pdf/nihms553425.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32190621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stereotactic Ablative Radiotherapy (SABR): Impact on the Immune System and Potential for Future Therapeutic Modulation.","authors":"A. Reese, S. Feigenberg, Azmat Husain, Tonya J. Webb, P. Hausner, M. Edelman, J. Feliciano, K. Tkaczuk, N. Sharma","doi":"10.4255/MCPHARMACOL.13.04","DOIUrl":"https://doi.org/10.4255/MCPHARMACOL.13.04","url":null,"abstract":"Stereotactic ablative radiotherapy (SABR) has been demonstrated to provide excellent local control in several malignancies. Recent reports have suggested that this ablative dose may impact disease outside of the radiated area. Furthermore, these studies have implicated immune modulation as the primary mechanism of disease response outside the irradiated area. More specifically, T-cell stimulation and tumor necrosis factor-α modulation following high dose irradiation have been suggested as the responsible components of this phenomenon. In addition, the \"abscopal effect\" may play a role in disease response outside of the radiated area. We review the current literature regarding the effects of ablative radiation therapy, the potential for immune modulation from it, and the mechanisms of the distant effects it elicits.","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"55 1","pages":"19-25"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74545671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromatin Modulation by Histone Deacetylase Inhibitors: Impact on Cellular Sensitivity to Ionizing Radiation.","authors":"France Carrier","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>It is well established that cells are more sensitive to ionizing radiation during the G₂/M phase of the cell cycle when their chromatin is highly compacted. However, highly compacted chromatin is less susceptible to DNA Double Strand Breaks (DSBs) than relaxed chromatin. Therefore, it is now becoming apparent that it is the cell capacity to repair its damaged DNA and refold its chromatin into its original compacted status that primarily affects the overall cellular sensitivity to ionizing radiation. The Histone Deacetylase Inhibitors (HDACIs) are a new class of anticancer agents that relax chromatin structure by increasing the levels of histone acetylation. The effect of HDACIs on normal and cancer cells sensitivity to ionizing radiation differs. Reports have indicated that HDACIs can protect normal cells while simultaneously sensitize cancer cells to ionizing radiation. This difference may stem from the individual characteristic of the normal and cancer cells chromatin structure. This review discusses this possibility and addresses the role of HDACIs in radiation therapy.</p>","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"5 1","pages":"51-59"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955893/pdf/nihms553411.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32190622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A main role for metabotropic glutamate receptor 1 in the neuroprotective effect of estrogen","authors":"S. Spampinato, S. Merlo, F. Nicoletti, M. Sortino","doi":"10.4255/MCPHARMACOL.12.06","DOIUrl":"https://doi.org/10.4255/MCPHARMACOL.12.06","url":null,"abstract":"Estrogen exerts neuroprotective activity under different experimental conditions through classical nuclear receptors, but mainly receptors expressed at the cell surface. Transducing mechanisms activated by these membrane estrogen receptors in the brain have been intensely investigated and, among others, interaction with G-protein coupled, metabotropic glutamate (mGlu) receptors has been considered. Besides mediating physiological estrogen functions, such as regulation of hormone production or sexual behavior in the hypothalamus, mGlu receptors, specifically mGlu1 receptor subtype, take part to the protective effect of estrogen in a model of neuronal toxicity induced by β-amyloid peptide. Coupling of estrogen receptor to mGlu1 receptor is supported by co-immunoprecipitation, similar neuroprotective effect induced by either receptor activation, lack of additivity when the two receptors are activated at the same time and prevention of the protective effect when antagonists of the other receptor are used, i.e. reduction of the protective effect of estrogen by the mGlu1 receptor antagonist and vice versa. In addition, the phosphatidylinositol-3 kinase/Akt pathway may represent the common signaling pathway to produce neuroprotection. These data introduce a novel view of the mechanisms underlying the neuroprotective activity of estrogen and open new perspectives also for future pharmacological interventions. Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ \u0000 table.MsoNormalTable \u0000 {mso-style-name:\"Table Normal\"; \u0000 mso-tstyle-rowband-size:0; \u0000 mso-tstyle-colband-size:0; \u0000 mso-style-noshow:yes; \u0000 mso-style-priority:99; \u0000 mso-style-parent:\"\"; \u0000 mso-padding-alt:0in 5.4pt 0in 5.4pt; \u0000 mso-para-margin-top:0in; \u0000 mso-para-margin-right:0in; \u0000 mso-para-margin-bottom:10.0pt; \u0000 mso-para-margin-left:0in; \u0000 line-height:150%; \u0000 mso-pagination:widow-orphan; \u0000 font-size:12.0pt; \u0000 font-family:\"Calibri\",\"sans-serif\"; \u0000 mso-ascii-font-family:Calibri; \u0000 mso-ascii-theme-font:minor-latin; \u0000 mso-hansi-font-family:Calibri; \u0000 mso-hansi-theme-font:minor-latin;}","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"2004 1","pages":"61-67"},"PeriodicalIF":0.0,"publicationDate":"2012-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86263723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA Regulation of Smooth Muscle Phenotype.","authors":"Sachindra R Joshi,&nbsp;Brian S Comer,&nbsp;Jared M McLendon,&nbsp;William T Gerthoffer","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Advances in studies of microRNA (miRNA) expression and function in smooth muscles illustrate important effects of small noncoding RNAs on cell proliferation, hypertrophy and differentiation. An emerging theme in miRNA research in a variety of cell types including smooth muscles is that miRNAs regulate protein expression networks to fine tune phenotype. Some widely expressed miRNAs have been described in smooth muscles that regulate important processes in many cell types, such as miR-21 control of proliferation and cell survival. Other miRNAs that are prominent regulators of smooth muscle-restricted gene expression also have targets that control pluripotent cell differentiation. The miR-143~145 cluster which targets myocardin and Kruppel-like factor 4 (KLF4) is arguably the best-described miRNA family in smooth muscles with profound effects on gene expression networks that promote serum response factor (SRF)-dependent contractile and cytoskeletal protein expression and the mature contractile phenotype. Kruppel-family members KLF4 and KLF5 have multiple effects on cell differentiation and are targets for multiple miRNAs in smooth muscles (miR-145, miR-146a, miR-25). The feedback and feedforward loops being defined appear to contribute significantly to vascular and airway remodeling in cardiovascular and respiratory diseases. RNA interference approaches applied to animal models of vascular and respiratory diseases prove that miRNAs and RNA-induced silencing are valid targets for novel anti-remodeling therapies that alter pathological smooth muscle hyperplasia and hypertrophy.</p>","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"4 1","pages":"1-16"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190587/pdf/nihms553424.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32742670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Expression of Key Signaling Proteins in MCF10 Cell Lines, a Human Breast Cancer Progression Model.","authors":"Jae Young So,&nbsp;Hong Jin Lee,&nbsp;Pavel Kramata,&nbsp;Audrey Minden,&nbsp;Nanjoo Suh","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Breast cancer is a heterogeneous disease that develops through a multistep process whose molecular basis remains poorly understood. The molecular mechanisms of breast cancer progression have been extensively studied using the MCF10 model. We summarized recent results on differential expression of proteins in the MCF10 cell series - MCF10A, MCF10AT1, MCF10DCIS.com and MCF10CA1a - and compared the ability of the latter 3 lines to form tumors in immunodeficient mice. In addition, we also investigated expression of several key signaling proteins in the MCF10 cell series corresponding to different stages of breast cancer progression. MCF10DCIS.com and MCF10CA1a cells were highly tumorigenic; MCF10CA1a cells showed more aggressive tumor growth than MCF10DCIS.com cells. HRAS-driven cancer initiation stage was accompanied by the increased expression of c-Myc, cyclin D1 and IGF-IR. Tumorigenic cell lines expressed higher levels of pErk, pAkt, Stat3 and Pak4 compared to nontumorigenic cells. The expression of CD44v, CD44v3, CD44v6, ERBB2, Cox2 and Smad4 correlated with the increased tumorigenicity of the MCF10 cell lines. The differences in expression of signaling proteins involved in breast cancer progression may provide new insight into the mechanisms of tumorigenesis and useful information for development of targeted therapeutics.</p>","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"4 1","pages":"31-40"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3928091/pdf/nihms553426.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32143473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA and cytokines","authors":"Xiangde Liu, S. Rennard","doi":"10.4255/MCPHARMACOL.11.19","DOIUrl":"https://doi.org/10.4255/MCPHARMACOL.11.19","url":null,"abstract":"Cytokines are involved in the development of cancer and chronic inflammatory lung diseases such as chronic obstructive pulmonary disease (COPD). MicroRNAs can regulate cytokine expression either by directly binding to a target sequence in a cytokine mRNA or by indirectly regulating a cluster of adenine and uridine-rich element binding proteins (ARE-BPs). Alternatively, cytokines, in particular the pro-inflammatory cytokines IL-1ß and TNF-α, can also regulate expression of miRNAs. In this regard, expression of miR-146a is dramatically increased in response to the stimulation of inflammatory cytokines in many cell types including human bronchial epithelial cells (HBECs) and human lung fibroblasts. Aberrant up-regulation of miR-146a in HBECs may provide a link between chronic inflammation and lung cancer or peri-bronchial fibrosis, while down-regulation of miR-146a in lung fibroblasts from COPD may account for deficient repair mediated by lung fibroblasts in emphysema.","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"98 1","pages":"143-151"},"PeriodicalIF":0.0,"publicationDate":"2011-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80749144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}