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The electrostatic attraction between the negatively charged components of cancer cells and the positively charged anticancer peptides (ACPs) is believed to play a role in selective disruption of cancer cell membrane. Since arginin...
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The electrostatic attraction between the negatively charged components of cancer cells and the positively charged anticancer peptides (ACPs) is believed to play a role in selective disruption of cancer cell membrane. Since arginine (Arg), a cationic amino acid is the most prevalent in these ACPs; we hypothesized that Arg when delivered in saline environment at the pharmacological concentration could become an anticancer molecule. The effects of L-Arg and D-Arg on tumor cell lines were studied. The therapeutic ability of pharmacological doses of Arg in saving the mice from experimental tumors was also evaluated. Both the enantiomers of Arg and not the cationic amino acid L-lysine (L-Lys) or agmatine-sulphate, at 10 mM concentration caused tumor cell clumping when treated in PBS. Arg delivered in PBS (Arg- P) and not in medium (Arg-M) up to 50 mM caused extensive tumor cell membrane damage leading to its death. Arg at 150 mM and above irrespective of chirality and incubation vehicle became an effective antitumor molecule against all the four cell lines tested. L-Arg was not toxic to normal cells like erythrocytes, lymphocytes, NIH 3T3 cells when presented in PBS. Arg cured mice bearing solid tumor fibrosarcoma (FS) when delivered into the tumor either in PBS or medium and lymphosarcoma-ascitic (LSA) tumor when delivered intraperitoneally in PBS. Our studies indicate that Arg can be used for loco-regional tumor therapy with minimal damage to normal cells and the mechanism of anticancer action of Arg is not metabolically driven but through its chemical structure, dose and delivery environment.
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Alternative splicing of mRNA precursors allows the synthesis of multiple mRNAs from a single primarytranscript, thus contributing to proteomic diversity in higher eukaryotes. Multiple studies demonstrate that alternativesplicing p...
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Alternative splicing of mRNA precursors allows the synthesis of multiple mRNAs from a single primarytranscript, thus contributing to proteomic diversity in higher eukaryotes. Multiple studies demonstrate that alternativesplicing patterns are altered during cancer progression. Several different mechanisms can contribute to changes in theregulation of alternative splicing. This report will provide an overview of how splicing microarrays and large-scalesequencing are being used to identify splicing changes in breast and prostate cancer. Global analyses of splice variantshave identified cancer-specific splice variant patterns that have potential use as biomarkers and potentially haveprognostic value as well as may represent novel therapeutic targets. A description of specific splice variants withdifferential expression in these cancers and their possible functions will be presented.
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For over 70 years, long chain fatty acids have been implicated in the development and progression of breastcancer. Although the exact role remains to be elucidated, dietary factors have been implicated in approximately 35% ofcance...
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For over 70 years, long chain fatty acids have been implicated in the development and progression of breastcancer. Although the exact role remains to be elucidated, dietary factors have been implicated in approximately 35% ofcancer deaths. Currently, biomarker, animal and in vitro studies suggest that the individual fatty acids have differing rolesin the promotion or prevention of breast cancer development and progression. The goal of this review is to assessepidemiological, animal and cellular studies with respect to the role of dietary long chain fatty acids in breast cancer risk.Subsequently we identify the common findings in these studies, discuss important factors that may influence humanstudies and evaluate the current dietary fat recommendations with respect to these findings.
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Background:Transforming growth factor-beta1 (TGF-β1) is a pleiotropic cytokine with a double role in cancer through its capacity to inhibit early stages of tumors while enhancing tumor progression at late stages of tumor progress...
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Background:Transforming growth factor-beta1 (TGF-β1) is a pleiotropic cytokine with a double role in cancer through its capacity to inhibit early stages of tumors while enhancing tumor progression at late stages of tumor progression. Moreover, TGF-β1 is a potent immunosuppressive cytokine within the tumor microenvironment that allows cancer cells to escape from immune surveillance, which largely contributes to the tumor progression.
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With the exception of a few anticancer agents, most breast cancer chemotherapeutics currently used havedevastating effects on normal cells. We investigated the effectiveness of the natural product NI-07, derived from Arctiumlappa,...
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With the exception of a few anticancer agents, most breast cancer chemotherapeutics currently used havedevastating effects on normal cells. We investigated the effectiveness of the natural product NI-07, derived from Arctiumlappa,to determine its killing potential on breast cancer cells and its cytotoxic effects in breast normal cells. The breastcancer cell lines HCC1419, MCF7, MDA-MB-231, MDA-MB-468, SKBR3, the normal mammary epithelial cell lineHME 50 HT and the normal mammary fibroblast cell line CCD-1074sk were analyzed in concurrently treated cultures ofNI-07, Taxol? or Untreated. NI-07- treated and Taxol? -treated cells were cultured for two weeks to assess cellresistance/recovery. Cell viability was determined by cell counts, Trypan Blue exclusion and microscopy. Additionally,cell viability and cytotoxicity were measured by XTT. Statistical significance (p ≤ 0.05) of NI-07 to Untreated or Taxol?was first determined using Two-Way ANOVA. Identified significant differences were further analyzed by One-WayANOVA and Tukey's test for honestly significant differences. The effect size of NI-07 compared to untreated or Taxol?was determined using Cohen's d. Our results showed significant declines in cell viability occurring in NI-07- treatedcancer cells after 48 hours of treatment in contrast to the more rapid effect of Taxol? (<24h). Additionally, cancer cellrecovery was less effective in NI-07 versus Taxol?. Furthermore, NI-07 showed no cytotoxicity in normal cells. Thislack of cytotoxicity, coupled with its killing efficiency in cancer cells, suggests that NI-07 could potentially make a stronganti-cancer compound or neo-adjuvant to current chemotherapy-based treatments.
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The most integrated approach toward understanding the multiple molecular events and mechanisms by which cancer may develop is the application of gene expression profiling using microarray technologies. As molecular alterations in ...
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The most integrated approach toward understanding the multiple molecular events and mechanisms by which cancer may develop is the application of gene expression profiling using microarray technologies. As molecular alterations in breast cancer are complex and involve cross-talk between multiple cellular signalling pathways, microarray technology provides a means of capturing and comparing the expression patterns of the entire genome across multiple samples in a high throughput manner. Since the development of microarray technologies, together with the advances in RNA extraction methodologies, gene expression studies have revolutionised the means by which genes suitable as targets for drug development and individualised cancer treatment can be identified. As of the mid-1990s, expression microarrays have been extensively applied to the study of cancer and no cancer type has seen as much genomic attention as breast cancer. The most abundant area of breast cancer genomics has been the clarification and interpretation of gene expression patterns that unite both biological and clinical aspects of tumours. It is hoped that one day molecular profiling will transform diagnosis and therapeutic selection in human breast cancer toward more individualised regimes. Here, we review a number of prominent microarray profiling studies focussed on human breast cancer and examine their strengths, their limitations, clinical implications including prognostic relevance and gene signature significance along with potential improvements for the next generation of microarray studies.
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Breast cancer is one of the most common diseases treated by general and plastic surgeons. Reconstruction of the breast began in the 1960s with the invention of the silicone breast implant. Since then, breast reconstruction has und...
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Breast cancer is one of the most common diseases treated by general and plastic surgeons. Reconstruction of the breast began in the 1960s with the invention of the silicone breast implant. Since then, breast reconstruction has undergone an evolution. It is possible to add a woman's own tissue to enhance an implant reconstruction, as in the latissimus dorsi myocutaneous flap, but often autologous tissue alone is sufficient to create a breast. Initially this was performed using abdominal tissue based on one of the rectus abdominis muscles and the superior epigastric system known as the TRAM (transverse rectus abdominis myocutaneous) flap. Now the same tissue is often transplanted as a free tissue transfer based on the deep inferior epigastric vessels. Strides have been made to lessen the morbidity on the abdominal wall with muscle-preserving operations to include the muscle-sparing TRAM, deep inferior epigastric perforator (DIEP) flap, and superficial inferior epigastric artery (SIEA) flaps. Similarly, in certain situations, gluteal tissue and inner thigh skin and fat can be used to reconstruct a breast, superior and inferior gluteal artery (SGAP/IGAP) flap and transverse upper gracilis (TUG) flaps respectively. The complications of each of these forms of breast reconstruction are reviewed as well. Breast reconstruction often now includes surgery to the noncancerous breast as well, as prophylactic mastectomy is becoming a more popular choice for women. In addition, the effects of radiation in breast conservation therapy are becoming evident and strides are being made to improve cosmetic outcome through breast rearrangement and reduction strategies. Through an alliance among the general and reconstructive surgeons, women ? s breast cancer needs can be addressed in an individualized manner.
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DNA vaccination appears a very attractive approach for inducing immune responses towards the encoded antigen,but studies in large animals and in humans revealed weaknesses of such responses. In this study, we evaluated a newapproa...
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DNA vaccination appears a very attractive approach for inducing immune responses towards the encoded antigen,but studies in large animals and in humans revealed weaknesses of such responses. In this study, we evaluated a newapproach based on a new device combining DNA vaccination with electroporation (EP) at the ear pinna site. Under optimalEP conditions, the expression of the DNA encoded antigen and the induced immune responses were considerably increased.Very interestingly, DNA vaccination using EP at the ear pinna induced much stronger cellular immune responsesthan at the flank skin although antigen expression was similar at both sites. As compared to vaccination at the ear pinnawithout EP, IFN- but not IL-4 production by splenocytes from immunized mice was significantly enhanced. In contrast,IL-4 but not IFN- production was increased by EP at the flank skin. The vaccination site of the ear pinna combined withEP route even provided therapeutic effects in a mouse tumor model.In conclusion, this study highlights the ear pinna as a privileged site for the induction of strong Th1 polarized cellular immunityagainst a defined antigen when combining DNA vaccination with EP.
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Specific reports have linked GPC3 with cancer. Its usefulness as a marker has been proved forhepatocarcinoma, melanoma and ovary carcinoma. However, there are no studies analyzing GPC3 usefulness as abiomarker in mammary tumors. T...
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Specific reports have linked GPC3 with cancer. Its usefulness as a marker has been proved forhepatocarcinoma, melanoma and ovary carcinoma. However, there are no studies analyzing GPC3 usefulness as abiomarker in mammary tumors. The aim of this work was to analyze GPC3 expression in breast tissues and to determinewhether it might be useful as a biomarker in breast cancer patients. Expression level of GPC3 mRNA in Brazilian andArgentine human breast tumor (n=121) and peritumoral “normal” tissue (n=77) samples was analyzed using qRT-PCR.GPC3 protein expression was analyzed from 69 breast cancer and 10 peritumoral samples using IHC. Statistical analyseswere done to evaluate the clinical-pathological significance of GPC3 expression. We found that Brazilian and Argentinepopulations are statistically different regarding GPC3 mRNA expression. In Argentine patients a lower GPC3 mRNAexpression was found in tumors as compared to peritumoral tissues. No association was found between GPC3 mRNA andprotein expression and the clinical-pathological parameters. The Kaplan-Meier curves suggested that elevated levels ofGPC3 mRNA are associated with relapse. Our results indicate differential expression of GPC3 in mammary tumors incomparasion to normal breast tissues. They also suggest the potential role of GPC3 as a biomarker and the importance ofdeepening the study.
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