Understanding Chemistry

AMINO ACIDS and OTHER BIOCHEMISTRY MENU Amino acids Background . . . An introduction to amino acids including their physical properties. Acid-base reactions of amino acids . . . Amino acids as zwitterions and the influence of this on their reactions with acids and bases. Proteins The structure of proteins . . . A brief introduction to protein structure including primary, secondary and tertiary structure. Hydrolysis of proteins . . . Hydrolysing proteins using hydrochloric acid. Proteins as enzymes . . . A simple introduction to how enzymes act as catalysts. The page assumes a knowledge of protein structure. The effect of changing conditions on enzyme catalysis . . . An explanation of the effect of substrate concentration, temperature and pH on enzymes. This page follows on from the "Proteins as enzymes" page. Enzyme inhibitors . . . A look at various ways in which enzymes can be prevented from catalysing their reactions. This also follows on from the "Proteins as enzymes" page. DNAThese pages are designed to be read in sequence. Later pages will assume knowledge of what has gone before. The structure of DNA . . . The replication of DNA . . . The transcription of DNA into messenger RNA . . . The genetic code . . . Protein synthesis . . . DNA mutations . . . Go to menu of other organic compounds . . . Go to Main Menu . . .

------------------------------------------ Best Wishes: Dr.Ehab Aboueladab, Tel:01007834123 Email:ehab10f@gmail.com,ehababoueladab@yahoo.com ------------------------------------------

PROTEINS AS ENZYMES

This page is an introduction to how proteins can work as enzymes - biological catalysts. You should realise that this is written to cover the needs of a number of UK-based chemistry syllabuses for 16 - 18 year olds. If you want detailed knowledge about enzymes for a biology or biochemistry course, you are probably in the wrong place! This is just an introduction.
Enzymes as catalystsEnzymes are mainly globular proteins - protein molecules where the tertiary structure has given the molecule a generally rounded, ball shape (although perhaps a very squashed ball in some cases). The other type of proteins (fibrous proteins) have long thin structures and are found in tissues like muscle and hair. We aren't interested in those in this topic. These globular proteins can be amazingly active catalysts. You are probably familiar with the use of catalysts like manganese(IV) oxide in decomposing hydrogen peroxide to give oxygen and water. The enzyme catalase will also do this - but at a spectacular rate compared with inorganic catalysts. One molecule of catalase can decompose almost a hundred thousand molecules of hydrogen peroxide every second. That's very impressive! This is a model of catalase, showing the globular structure - a bit like a tangled mass of string:
An important point about enzymes is that they are very specific about what they can catalyse. Even small changes in the reactant molecule can stop the enzyme from catalysing its reaction. The reason for this lies in the active site present in the enzyme . . . Active sites Active sites are cracks or hollows on the surface of the enzyme caused by the way the protein folds itself up into its tertiary structure. Molecules of just the right shape, and with just the right arrangement of attractive groups (see later) can fit into these active sites. Other molecules won't fit or won't have the right groups to bind to the surface of the active site. The usual analogy for this is a key fitting into a lock. For the key to work properly it has to fit exactly into the lock. In chemistry, we would describe the molecule which is actually going to react (the purple one in the diagram) as the reactant. In biology and biochemistry, the reactant in an enzyme reaction is known instead as the substrate. You mustn't take this picture of the way a substrate fits into its enzyme too literally. What is just as important as the physical shape of the substrate are the bonds which it can form with the enzyme. Enzymes are protein molecules - long chains of amino acid residues. Remember that sticking out all along those chains are the side groups of the amino acids - the "R" groups that we talked about on the page about protein structure. Active sites, of course, have these "R" groups lining them as well - typically from about 3 to 12 in an active site. The next diagram shows an imaginary active site: Remember that these "R" groups contain the sort of features which are responsible for the tertiary structure in proteins. For example, they may contain ionic groups like -NH3+ or -COO-, or -OH groups which can hydrogen bond, or hydrocarbon chains or rings which can contribute to van der Waals forces. Groups like these help a substrate to attach to the active site - but only if the substrate molecule has an arrangement of groups in the right places to interact with those on the enzyme. The diagram shows a possible set of interactions involving two ionic bonds and a hydrogen bond. The groups shown with + or - signs are obvious. The ones with the "H"s in them are groups capable of hydrogen bonding. It is possible that one or more of the unused "R" groups in the active site could also be helping with van der Waals attractions between them and the substrate. If the arrangement of the groups on the active site or the substrate was even slightly different, the bonding almost certainly wouldn't be as good - and in that sense, a different substrate wouldn't fit the active site on the enzyme. This process of the catalyst reacting with the substrate and eventually forming products is often summarised as: . . . where E is the enzyme, S the substrate and P the products. The formation of the complex is reversible - the substrate could obviously just break away again before it converted into products. The second stage is shown as one-way, but might be reversible in some cases. It would depend on the energetics of the reaction. So why does attaching itself to an enzyme increase the rate at which the substrate converts into products? It isn't at all obvious why that should be - and most sources providing information at this introductory level just gloss over it or talk about it in vague general terms (which is what I am going to be forced to do, because I can't find a simple example to talk about!). Catalysts in general (and enzymes are no exception) work by providing the reaction with a route with a lower activation energy. Attaching the substrate to the active site must allow electron movements which end up in bonds breaking much more easily than if the enzyme wasn't there. Strangely, it is much easier to see what might be happening in other cases where the situation is a bit more complicated . . . Enzyme cofactors What we have said so far is a major over-simplification for most enzymes. Most enzymes aren't in fact just pure protein molecules. Other non-protein bits and pieces are needed to make them work. These are known as cofactors. In the absence of the right cofactor, the enzyme doesn't work. For those of you who like collecting obscure words, the inactive protein molecule is known as an apoenzyme. When the cofactor is in place so that it becomes an active enzyme, it is called aholoenzyme.
There are two basically different sorts of cofactors. Some are bound tightly to the protein molecule so that they become a part of the enzyme - these are called prosthetic groups. Some are entirely free of the enzyme and attach themselves to the active site alongside the substrate - these are called coenzymes. Prosthetic groups Prosthetic groups can be as simple as a single metal ion bound into the enzyme's structure, or may be a more complicated organic molecule (which might also contain a metal ion). The enzymescarbonic anhydrase and catalase are simple examples of the two types. Zinc ions in carbonic anhydrase Carbonic anhydrase is an enzyme which catalyses the conversion of carbon dioxide into hydrogencarbonate ions (or the reverse) in the cell. (If you look this up elsewhere, you will find that biochemists tend to persist in calling hydrogencarbonate by its old name, bicarbonate!) In fact, there are a whole family of carbonic anhydrases all based around different proteins, but all of them have a zinc ion bound up in the active site. In this case, the mechanism is well understood and simple. We'll look at this in some detail, because it is a good illustration of how enzymes work.
The zinc ion is bound to the protein chain via three links to separate histidine residues in the chain - shown in pink in the picture of one version of carbonic anhydrase. The zinc is also attached to an -OH group - shown in the picture using red for the oxygen and white for the hydrogen.
The structure of the amino acid histidine is . . . . . . and when it is a part of a protein chain, it is joined up like this: If you look at the model of the arrangement around the zinc ion in the picture above, you should at least be able to pick out the ring part of the three molecules. The zinc ion is bound to these histidine rings via dative covalent (co-ordinate covalent) bonds from lone pairs on the nitrogen atoms. Simplifying the structure around the zinc . . . The arrangement of the four groups around the zinc is approximately tetrahedral. Notice that I have distorted the usual roughly tetrahedral arrangement of electron pairs around the oxygen - that's just to keep the diagram as clear as possible. So that's the structure around the zinc. How does this catalyse the reaction between carbon dioxide and water? A carbon dioxide molecule is held by a nearby part of the active site so that one of the lone pairs on the oxygen is pointing straight at the carbon atom in the middle of the carbon dioxide molecule. Attaching it to the enzyme also increases the existing polarity of the carbon-oxygen bonds. If you have done any work on organic reaction mechanisms at all, then it is pretty obvious what is going to happen. The lone pair forms a bond with the carbon atom and part of one of the carbon-oxygen bonds breaks and leaves the oxygen atom with a negative charge on it. What you now have is a hydrogencarbonate ion attached to the zinc. The next diagram shows this broken away and replaced with a water molecule from the cell solution. All that now needs to happen to get the catalyst back to where it started is for the water to lose a hydrogen ion. This is transferred by another water molecule to a nearby amino acid residue with a nitrogen in the "R" group - and eventually, by a series of similar transfers, out of the active site completely. . . . and the carbonic anhydrase enzyme can do this sequence of reactions about a million times a second. This is a wonderful piece of molecular machinery! Let me repeat yet again: If you are doing a UK-based chemistry exam for 16 - 18 year olds, you are unlikely to need details of this reaction. I've talked it through in some detail to show that although enzymes are complicated molecules, all they do is some basic chemistry. It is just that this particular example is a lot easier to understand than most! The haem (US: heme) group in catalase Remember the model of catalase from further up the page . . . At the time, I mentioned the non-protein groups which this contains, shown in pink in the picture. These are haem (US: heme) groups bound to the protein molecule, and an essential part of the working of the catalase. The haem group is a good example of a prosthetic group. If it wasn't there, the protein molecule wouldn't work as a catalyst. The haem groups contain an iron(III) ion bound into a ring molecule - one of a number of related molecules called porphyrins. The iron is locked into the centre of the porphyrin molecule via dative covalent bonds from four nitrogen atoms in the ring structure. There are various types of porphyrin, so there are various different haem groups. The one we are interested in is called haem B, and a model of the haem B group (with the iron(III) ion in grey at the centre) looks like this:
The reaction that catalase carries out is the decomposition of hydrogen peroxide into water and oxygen. A lot of work has been done on the mechanism for this reaction, but I am only going to give you a simplified version rather than describe it in full. Although it looks fairly simple on the surface, there are a lot of hidden things going on to complicate it. Essentially the reaction happens in two stages and involves the iron changing its oxidation state. An easy change of oxidation state is one of the main characteristics of transition metals. In the lab, iron commonly has two oxidation states (as well as zero in the metal itself), +2 and +3, and changes readily from one to the other. In catalase, the change is from +3 to the far less common +4 and back again. In the first stage there is a reaction between a hydrogen peroxide molecule and the active site to give: The "Enzyme" in the equation refers to everything (haem group and protein) apart from the iron ion. The "(III)" and "(IV)" are the oxidation states of the iron in both cases. This equation (and the next one) are NOT proper chemical equations. They are just summaries of the most obvious things which have happened. The new arrangement around the iron then reacts with a second hydrogen peroxide to regenerate the original structure and produce oxygen and a second molecule of water. What is hidden away in this simplification are the other things that are happening at the same time - for example, the rest of the haem group and some of the amino acid residues around the active site are also changed during each stage of the reaction. And if you think about what has to happen to the hydrogen peroxide molecule in both reactions, it has to be more complicated than this suggests. Hydrogen peroxide is joined up as H-O-O-H, and yet both hydrogens end up attached to the same oxygen. That is quite a complicated thing to arrange in small steps in a mechanism, and involves hydrogen ions being transferred via amino acids residues in the active site. So do you need to remember all this for chemistry purposes at this level? No - not unless your syllabus specifically asks you for it. It is basically just an illustration of the term "prosthetic group". It also shows that even in a biochemical situation, transition metals behave in the same sort of way as they do in inorganic chemistry - they form complexes, and they change their oxidation state. And if you want to follow this up to look in detail at what is happening, you will find the same sort of interactions around the active site that we looked at in the simpler case of carbonic anydrase. (But please don't waste time on this unless you have to - it is seriously complicated!) Coenzymes Coenzymes are another form of cofactor. They are different from prosthetic groups in that they aren't permanently attached to the protein molecule. Instead, coenzymes attach themselves to the active site alongside the substrate, and the reaction involves both of them. Once they have reacted, they both leave the active site - both changed in some way. A simple diagram showing a substrate and coenzyme together in the active site might look like this: It is much easier to understand this with a (relatively) simple example. NAD+ as coenzyme with alcohol dehydrogenase Alcohol dehydrogenase is an enzyme which starts the process by which alcohol (ethanol) in the blood is oxidised to harmless products. The name "dehydrogenase" suggests that it is oxidising the ethanol by removing hydrogens from it. The reaction is actually between ethanol and the coenzyme NAD+ attached side-by-side to the active site of the protein molecule. NAD+ is a commonly used coenzyme in all sorts of redox reactions in the cell. NAD+ stands for nicotinamide adenine dinucleotide. The plus sign which is a part of its name is because it carries a positive charge on a nitrogen atom in the structure. The "nicotinamide" part of the structure comes from the vitamin variously called vitamin B3, niacin or nicotinic acid. Several important coenzymes are derived from vitamins.

------------------------------------------ Best Wishes: Dr.Ehab Aboueladab, Tel:01007834123 Email:ehab10f@gmail.com,ehababoueladab@yahoo.com ------------------------------------------

4 تك: سترة اليكترونية تجري مكالمات هاتفية

------------------------------------------Best Wishes: Dr.Ehab Aboueladab, Tel:01007834123 Email:ehab10f@gmail.com,ehababoueladab@yahoo.com ------------------------------------------

Breast Cancer

CME Chemotherapy for Women With Heavily Pre-treated Metastatic Breast Cancer. A Review of the Evidence Base. /cme/Chemotherapy_for_Women_With_Heavily_Pre_treated_Metastatic_Breast_Cancer_A_Review_of_the_Evidence_Base.html/cme/Chemotherapy_for_Women_With_Heavily_Pre_treated_Metastatic_Breast_Cancer_A_Review_of_the_Evidence_Base.htmltcm:8-282050-64Chemotherapy for Women With Heavily Pre-treated Metastatic Breast Cancer. A Review of the Evidence Base.Chemotherapy for Women With Heavily Pre-treated Metastatic Breast Cancer. A Review of the Evidence Base.2012071720120717Chemotherapy for Women With Heavily Pre-treated Metastatic Breast Cancer. A Review of the Evidence Base.Chemotherapy for Women With Heavily Pre-treated Metastatic Breast Cancer. A Review of the Evidence Base.An interactive CME activity provided by the Elsevier Office of Continuing Medical EducationAn interactive CME activity provided by the Elsevier Office of Continuing Medical EducationCMECME1.01.0201309302013 Sept 30InteractiveBreastTreatmentChemotherapy for Women With Heavily Pre-treated Metastatic Breast Cancer. A Review of the Evidence Base. An interactive CME activity provided by the Elsevier Office of Continuing Medical Education The goals of this activity are to increase oncologists’ knowledge of the newest therapies and improve their competence in incorporating this knowledge into treatment planning. Duration February 12, 2012 to January 31, 2013 Credits A maximum of 1.0 AMA PRA Category 1 Credit™ Faculty Christopher Twelves, MD | Linda T. Vahdat, MD This course is not part of OncologySTAT. By clicking the button below you will be leaving this website. Chemotherapy for Women With Heavily Pre-treated Metastatic Breast Cancer. A Review of the Evidence Base. An interactive CME activity provided by the Elsevier Office of Continuing Medical Education The goals of this activity are to increase oncologists’ knowledge of the newest therapies and improve their competence in incorporating this knowledge into treatment plannin1 An interactive CME activity provided by the Elsevier Office of Continuing Medical Education
	News Age Ups Risk of Other Cancers in Breast Cancer Survivors /news/Age_Ups_Risk_of_Other_Cancers_in_Breast_Cancer_Survivors_US.html/news/Age_Ups_Risk_of_Other_Cancers_in_Breast_Cancer_Survivors_US.htmltcm:8-284422-64Age Ups Risk of Other Cancers in Breast Cancer SurvivorsAge Ups Risk of Other Cancers in Breast Cancer Survivors20121105Age Ups Risk of Other Cancers in Breast Cancer SurvivorsAge Ups Risk of Other Cancers in Breast Cancer SurvivorsS FreemanS Freeman201211052012 Nov 5IMNG Medical MediaIMNG Medical MediaBreastPrevention and ScreeningMANCHESTER, ENGLAND (IMNG) - Older women who are breast cancer survivors have a greater risk of developing additional primary cancers in the long term than those under 65 years of age, according to an analysis of data on more than 100,000 survivors in the United States.Women aged 70-79 years appear to have the highest risk of developing a multiple primary malignancy (MPM), with a crude 10-year incidence of 17.8/10,000 person-years. In comparisons, the rate of risk for survivors younger than 65 was... MANCHESTER, ENGLAND (IMNG) - Older women who are breast cancer survivors have a greater risk of developing additional primary cancers in the long term than those under 65 years of age, according to an analysis of data on more than 100,000 survivors in the United States. Women aged 70-79 years appear to have the highest risk of developing a multiple primary malignancy (MPM), with a crude 10-year incidence of 17.8/10,000 person-years. In comparisons, the rate of risk for survivors younger thNews120 IMNG Medical Media, 2012 Nov 5, S Freeman ASCO Update Keeps Breast Cancer Survivor Guidelines Intact /news/ASCO_Update_Keeps_Breast_Cancer_Survivor_Guidelines_Intact_US.html/news/ASCO_Update_Keeps_Breast_Cancer_Survivor_Guidelines_Intact_US.htmltcm:8-284430-64ASCO Update Keeps Breast Cancer Survivor Guidelines IntactASCO Update Keeps Breast Cancer Survivor Guidelines Intact20121105ASCO Update Keeps Breast Cancer Survivor Guidelines IntactASCO Update Keeps Breast Cancer Survivor Guidelines IntactT HaelleT Haelle201211052012 Nov 5IMNG Medical MediaIMNG Medical MediaBreastPrevention and ScreeningThe American Society of Clinical Oncology has issued updated recommendations for the follow-up care of breast cancer survivors, but made no changes from guidelines released in 2006.The current guidelines include recommendations for all oncologists, primary care providers, and nurses who treat asymptomatic breast cancer survivors. They emphasize physical exams, patient history, and mammography, but discourage routine blood tests, biomarker studies, and other imaging in the absence of symptoms.An American... The American Society of Clinical Oncology has issued updated recommendations for the follow-up care of breast cancer survivors, but made no changes from guidelines released in 2006. The current guidelines include recommendations for all oncologists, primary care providers, and nurses who treat asymptomatic breast cancer survivors. They emphasize physical exams, patient history, and mammography, but discourage routine blood tests, biomarker studies, and other imaging in the absence ofNews120 IMNG Medical Media, 2012 Nov 5, T Haelle Cardiac Toxicity Not Seen 25 Years after Breast Radiation /news/Cardiac_Toxicity_Not_Seen_25_Years_after_Breast_Radiation__US.html/news/Cardiac_Toxicity_Not_Seen_25_Years_after_Breast_Radiation__US.htmltcm:8-284346-64Cardiac Toxicity Not Seen 25 Years after Breast Radiation Cardiac Toxicity Not Seen 25 Years after Breast Radiation 20121101Cardiac Toxicity Not Seen 25 Years after Breast Radiation Cardiac Toxicity Not Seen 25 Years after Breast RadiationN OsterweilN Osterweil201211012012 Nov 1IMNG Medical MediaIMNG Medical MediaBreastTreatmentASTRO 2012BOSTON (IMNG) - Here's heartening news that physicians can convey to breast cancer survivors: Modern breast irradiation did not appear to cause late-term cardiac toxicity in a study that examined women a quarter of a century after they were treated.Investigators found no significant differences in Framingham Heart Study risk scores, hemodynamic parameters, pericardial thickening, or heart failure among 50 women who had been randomized in the 1970s and 1980s to either mastectomy or breast-conserving... BOSTON (IMNG) - Here's heartening news that physicians can convey to breast cancer survivors: Modern breast irradiation did not appear to cause late-term cardiac toxicity in a study that examined women a quarter of a century after they were treated. Investigators found no significant differences in Framingham Heart Study risk scores, hemodynamic parameters, pericardial thickening, or heart failure among 50 women who had been randomized in the 1970s and 1980s to either mastectomy or breastNews120 IMNG Medical Media, 2012 Nov 1, N Osterweil Triple-Negative Breast Cancer Shows Less Aggressive Biology in Elderly /news/TripleNegative_Breast_Cancer_Shows_Less_Aggressive_Biology_in_Elderly_US.html/news/TripleNegative_Breast_Cancer_Shows_Less_Aggressive_Biology_in_Elderly_US.htmltcm:8-284360-64Triple-Negative Breast Cancer Shows Less Aggressive Biology in ElderlyTriple-Negative Breast Cancer Shows Less Aggressive Biology in Elderly20121102Triple-Negative Breast Cancer Shows Less Aggressive Biology in ElderlyTriple-Negative Breast Cancer Shows Less Aggressive Biology in ElderlyS FreemanS Freeman201211012012 Nov 1IMNG Medical MediaIMNG Medical MediaBreastTreatmentMANCHESTER, ENGLAND (IMNG) - Older women with primary, operable, triple-negative breast cancer may have less aggressive tumor biology despite being treated for larger tumors than their younger counterparts, new data suggest.Tumor samples taken from women aged 70 years or older were found to be of lower grade with significantly lower expression of the tumor markers Ki67 and p53 than seen in younger women, investigators reported at the annual meeting of the International Society of Geriatric Oncology... MANCHESTER, ENGLAND (IMNG) - Older women with primary, operable, triple-negative breast cancer may have less aggressive tumor biology despite being treated for larger tumors than their younger counterparts, new data suggest. Tumor samples taken from women aged 70 years or older were found to be of lower grade with significantly lower expression of the tumor markers Ki67 and p53 than seen in younger women, investigators reported at the annual meeting of the International Society of GeriatrNews120 IMNG Medical Media, 2012 Nov 1, S Freeman Older Women Lived Longer With Radiotherapy After Lumpectomy /news/Older_Women_Lived_Longer_With_Radiotherapy_After_Lumpectomy__US.html/news/Older_Women_Lived_Longer_With_Radiotherapy_After_Lumpectomy__US.htmltcm:8-284334-64Older Women Lived Longer With Radiotherapy After Lumpectomy Older Women Lived Longer With Radiotherapy After Lumpectomy 20121031Older Women Lived Longer With Radiotherapy After LumpectomyOlder Women Lived Longer With Radiotherapy After LumpectomyN OsterweilN Osterweil201210312012 Oct 31IMNG Medical MediaIMNG Medical MediaBreastTreatmentASTRO 2012BOSTON (IMNG) - A review of data on nearly 30,000 women suggests older age by itself should not be a barrier to radiotherapy after lumpectomy for early-stage breast cancer.Older patients treated with both modalities had higher rates of overall and breast cancer - specific survival at 5 and 10 years compared with women who underwent lumpectomy alone , investigators reported at the annual meeting of the American Society for Radiation Oncology."The improvement in cause-specific survival with the addition... BOSTON (IMNG) - A review of data on nearly 30,000 women suggests older age by itself should not be a barrier to radiotherapy after lumpectomy for early-stage breast cancer. Older patients treated with both modalities had higher rates of overall and breast cancer - specific survival at 5 and 10 years compared with women who underwent lumpectomy alone , investigators reported at the annual meeting of the American Society for Radiation Oncology. "The improvement in cause-specific survivalNews120 IMNG Medical Media, 2012 Oct 31, N Osterweil Screening Cuts Breast Cancer Deaths by 20% /news/Screening_Cuts_Breast_Cancer_Deaths_by_20_US.html/news/Screening_Cuts_Breast_Cancer_Deaths_by_20_US.htmltcm:8-284308-64Screening Cuts Breast Cancer Deaths by 20%Screening Cuts Breast Cancer Deaths by 20%20121029Screening Cuts Breast Cancer Deaths by 20%Screening Cuts Breast Cancer Deaths by 20%J SmithJ Smith201210292012 Oct 29IMNG Medical MediaIMNG Medical MediaBreastPrevention and ScreeningWomen offered breast cancer screening have a 20% lower relative risk of dying from breast cancer than women not invited to participate in screening, a epidemiologic study in the Lancet from the United Kingdom has found.The study also found that women invited to screening are also more likely to be overdiagnosed, meaning that they are treated surgically for tumors that, if not for screening, would have caused no illness and remained undetected. The researchers cautioned, however, that their findings... Women offered breast cancer screening have a 20% lower relative risk of dying from breast cancer than women not invited to participate in screening, a epidemiologic study in the Lancet from the United Kingdom has found. The study also found that women invited to screening are also more likely to be overdiagnosed, meaning that they are treated surgically for tumors that, if not for screening, would have caused no illness and remained undetected. The researchers cautioned, however, that theNews120 IMNG Medical Media, 2012 Oct 29, J Smith FDA Panel Supports Approval of Hologic's C-View Software for 3D Digital Mammography /news/FDA_Panel_Supports_Approval_of_Hologics_CView_Software_for_3D_Digital_Mammography.html/news/FDA_Panel_Supports_Approval_of_Hologics_CView_Software_for_3D_Digital_Mammography.htmltcm:8-284241-64FDA Panel Supports Approval of Hologic's C-View Software for 3D Digital MammographyFDA Panel Supports Approval of Hologic's C-View Software for 3D Digital Mammography20121025FDA Panel Supports Approval of Hologic's C-View Software for 3D Digital MammographyFDA Panel Supports Approval of Hologic's C-View Software for 3D Digital MammographyR KernR Kern201210252012 Oct 25IMNG Medical MediaIMNG Medical MediaBreastPrevention and ScreeningThe benefits of Hologic’s C-View software for three-dimensional digital mammography exams with less radiation than the current process outweigh the risks, FDA’s Radiological Devices panel concluded in a 9-1 vote Oct. 24. The advisory panel also voted 9-1 that C-View demonstrated reasonable assurance of safety and efficacy.C-View is an imaging algorithm add-on for Hologic’s currently available Selenia Dimensions 3D digital mammography system that is designed to eliminate the need to perform a separate... The benefits of Hologic’s C-View software for three-dimensional digital mammography exams with less radiation than the current process outweigh the risks, FDA’s Radiological Devices panel concluded in a 9-1 vote Oct. 24. The advisory panel also voted 9-1 that C-View demonstrated reasonable assurance of safety and efficacy. C-View is an imaging algorithm add-on for Hologic’s currently available Selenia Dimensions 3D digital mammography system that is designed to eliminate the need to perNews120 IMNG Medical Media, 2012 Oct 25, R Kern NICE Backs Xgeva for Oncology But Excludes Prostate Cancer Indication /news/NICE_Backs_Xgeva_for_Oncology_But_Excludes_Prostate_Cancer_Indication.html/news/NICE_Backs_Xgeva_for_Oncology_But_Excludes_Prostate_Cancer_Indication.htmltcm:8-284247-64NICE Backs Xgeva for Oncology But Excludes Prostate Cancer IndicationNICE Backs Xgeva for Oncology But Excludes Prostate Cancer Indication20121025NICE Backs Xgeva for Oncology But Excludes Prostate Cancer IndicationNICE Backs Xgeva for Oncology But Excludes Prostate Cancer IndicationF KermaniF Kermani201210242012 Oct 24The Pink Sheet DailyThe Pink Sheet DailyBreastProstateSkeletal Related EventTreatmentSkeletal-Related EventsIn a rare occurrence for any drug navigating its way through the UK’s reimbursement system, Amgen Inc.’s Xgeva (denosumab) for the treatment of skeletal events in some cancer patients has fairly flown through the National Institute for Health and Clinical Excellence’s evaluation process. Although the company did not get everything it wanted from the health-cost regulator, the discount Amgen offered the NHS means that it can now rest assured that the uptake of Xgeva is only a brief matter of time. NICE... In a rare occurrence for any drug navigating its way through the UK’s reimbursement system, Amgen Inc.’s Xgeva (denosumab) for the treatment of skeletal events in some cancer patients has fairly flown through the National Institute for Health and Clinical Excellence’s evaluation process. Although the company did not get everything it wanted from the health-cost regulator, the discount Amgen offered the NHS means that it can now rest assured that the uptake of Xgeva is only a brief mattNews120 The Pink Sheet Daily, 2012 Oct 24, F Kermani
	Expert Opinion My Approach to Endocrine Therapy in Breast Cancer—Part I /viewpoints/my-approach/My_Approach_to_Endocrine_Therapy_in_Breast_Cancer_Part_I.html/viewpoints/my-approach/My_Approach_to_Endocrine_Therapy_in_Breast_Cancer_Part_I.htmltcm:8-283642-64My Approach to Endocrine Therapy in Breast Cancer—Part IMy Approach to Endocrine Therapy in Breast Cancer—Part I20120918My Approach to Endocrine Therapy in Breast Cancer—Part IMy Approach to Endocrine Therapy in Breast Cancer—Part IDaniel Hayes, MDDaniel Hayes, MD201209182012 Sept 18Interview by L Scott ZoellerInterview by L Scott ZoellerBreastER Positive BreastTreatmentIn Part I of this interview, Dr. Hayes discusses personalization and the optimal sequence of endocrine therapy in breast cancer. In Part II, Dr. Hayes discusses early vs late recurrence, extended therapy, and the potential for combination therapy.Personalized TherapyOncologySTAT: Would you discuss how modern adjuvant endocrine therapy is becoming increasingly personalized in breast cancer?Dr. Hayes: That depends on what one means by "personalized." My answer is I don’t think it is. I think we got... In Part I of this interview, Dr. Hayes discusses personalization and the optimal sequence of endocrine therapy in breast cancer. In Part II, Dr. Hayes discusses early vs late recurrence, extended therapy, and the potential for combination therapy. Personalized Therapy OncologySTAT: Would you discuss how modern adjuvant endocrine therapy is becoming increasingly personalized in breast cancer? Dr. Hayes: That depends on what one means by "personalized." My answer is I don’t think it is. I thiMy Approach26 Interview by L Scott Zoeller, 2012 Sept 18, Daniel Hayes, et al
	Journal Scans: Research Lapatinib Plus Capecitabine in Brain Metastases from HER2+ Breast Cancer /journals/journal_scans/Lapatinib_Plus_Capecitabine_in_Patients_With_Previously_Untreated_Brain_Metastases_from_HER2-positive_Metastatic_Breast_Cancer_(LANDSCAPE)_A_Single-group_Phase_2_Study.html/journals/journal_scans/Lapatinib_Plus_Capecitabine_in_Patients_With_Previously_Untreated_Brain_Metastases_from_HER2-positive_Metastatic_Breast_Cancer_(LANDSCAPE)_A_Single-group_Phase_2_Study.htmltcm:8-284473-64Lapatinib Plus Capecitabine in Patients With Previously Untreated Brain Metastases from HER2-positive Metastatic Breast Cancer (LANDSCAPE): A Single-group Phase 2 StudyLapatinib Plus Capecitabine in Patients With Previously Untreated Brain Metastases from HER2-positive Metastatic Breast Cancer (LANDSCAPE): A Single-group Phase 2 Study20121107Lapatinib Plus Capecitabine in Patients With Previously Untreated Brain Metastases from HER2-positive Metastatic Breast Cancer (LANDSCAPE): A Single-group Phase 2 StudyLapatinib Plus Capecitabine in Brain Metastases from HER2+ Breast CancerT Bachelot, G Romieu, M Campone, et alT Bachelot, G Romieu, M Campone, et al201211012012 Nov 1Lancet OncolLancet OncolBreastTreatmentNeurologic ComplicationsIn an update of the LANDSCAPE Phase II trial, a response rate of 65.9% was achieved with the combination of lapatinib and capecitabine when used as first-line therapy for HER2+ breast cancer with brain metastases. Abstract Background: Brain metastases occur in 30–50% of patients with metastatic HER2-positive breast cancer. In the case of diffuse brain metastases, treatment is based on whole brain radiotherapy (WBRT). Few systemic options are available. We aimed to investigate the combination of lapatinib plus capecitabine for the treatment of previously untreated brain metastases from HER2-positive breast cancer.Methods: In this single-arm phase 2, open-label, multicentre study, eligible patients had HER2-positive... Abstract Background: Brain metastases occur in 30–50% of patients with metastatic HER2-positive breast cancer. In the case of diffuse brain metastases, treatment is based on whole brain radiotherapy (WBRT). Few systemic options are available. We aimed to investigate the coJournal Scans149 Lancet Oncol, 2012 Nov 1, T Bachelot, et al Validating a Prognostic Scoring System for Postmastectomy Locoregional Recurrence /journals/journal_scans/Validating_a_Prognostic_Scoring_System_for_Postmastectomy_Locoregional_Recurrence_in_Breast_Cancer.html/journals/journal_scans/Validating_a_Prognostic_Scoring_System_for_Postmastectomy_Locoregional_Recurrence_in_Breast_Cancer.htmltcm:8-284475-64Validating a Prognostic Scoring System for Postmastectomy Locoregional Recurrence in Breast CancerValidating a Prognostic Scoring System for Postmastectomy Locoregional Recurrence in Breast Cancer20121107Validating a Prognostic Scoring System for Postmastectomy Locoregional Recurrence in Breast CancerValidating a Prognostic Scoring System for Postmastectomy Locoregional RecurrenceSHC Cheng, SY Tsai, B-L Yu, et alSHC Cheng, SY Tsai, B-L Yu, et al201211012012 Nov 1Int J Radiat Oncol Biol PhysInt J Radiat Oncol Biol PhysBreastDiagnosis and StagingResearchers sought to validate a previous scoring system to determine the necessity of postmastectomy radiation therapy in breast cancer patients with 1 to 3 positive lymph nodes. Abstract Purpose: This study is designed to validate a previously developed locoregional recurrence risk (LRR) scoring system and further define which groups of patients with breast cancer would benefit from postmastectomy radiation therapy (PMRT).Methods and Materials: An LRR risk scoring system was developed previously at our institution using breast cancer patients initially treated with modified radical mastectomy between 1990 and 2001. The LRR score comprised 4 factors: patient age, lymphovascular invasion,... Abstract Purpose: This study is designed to validate a previously developed locoregional recurrence risk (LRR) scoring system and further define which groups of patients with breast cancer would benefit from postmastectomy radiation therapy (PMRT). Methods and Materials: An LRR risk scoring system Journal Scans149 Int J Radiat Oncol Biol Phys, 2012 Nov 1, SHC Cheng, et al PTEN Loss Common in Trastuzumab Resistance in Breast Cancer /journals/journal_scans/Frequent_Mutational_Activation_of_the_PI3K-AKT_Pathway_in_Trastuzumab-Resistant_Breast_Cancer.html/journals/journal_scans/Frequent_Mutational_Activation_of_the_PI3K-AKT_Pathway_in_Trastuzumab-Resistant_Breast_Cancer.htmltcm:8-284362-64Frequent Mutational Activation of the PI3K-AKT Pathway in Trastuzumab-Resistant Breast CancerFrequent Mutational Activation of the PI3K-AKT Pathway in Trastuzumab-Resistant Breast Cancer20121102Frequent Mutational Activation of the PI3K-AKT Pathway in Trastuzumab-Resistant Breast CancerPTEN Loss Common in Trastuzumab Resistance in Breast CancerS Chandarlapaty, RA Sakr, D Giri, et alS Chandarlapaty, RA Sakr, D Giri, et al201210232012 Oct 23Clin Cancer ResClin Cancer ResBreastTreatmentIn a prospective study, a high percentage of trastuzumab-resistant HER2+ breast tumors had PTEN loss and activating mutations of the PI3K/AKT pathway, while loss of HER2 overexpression was rare. SUMMARY OncologySTAT Editorial Team Despite the efficacy of trastuzumab therapy in metastatic HER2-positive breast cancer, almost all patients eventually have disease progression. Determining the molecular basis for trastuzumab resistance has been hampered in part because of the difficulty in acquiring tumor samples from patients who progress while on trastuzumab. Possible explanations for trastuzumab resistance, based on retrospective studies and laboratory models, include activation of the PI3K/AKT pathway, in response to either... SUMMARY OncologySTAT Editorial Team Despite the efficacy of trastuzumab therapy in metastatic HER2-positive breast cancer, almost all patients eventually have disease progression. Determining the molecular basis for trastuzumab resistance has been hampered in part Journal Scans149 Clin Cancer Res, 2012 Oct 23, S Chandarlapaty, et al Treatment Response Biomarker Identified in Triple-Negative Breast Cancer /journals/journal_scans/Thymosin_Beta_15A_TMSB15A_is_a_Predictor_of_Chemotherapy_Response_in_Triple_Negative_Breast_Cancer.html/journals/journal_scans/Thymosin_Beta_15A_TMSB15A_is_a_Predictor_of_Chemotherapy_Response_in_Triple_Negative_Breast_Cancer.htmltcm:8-284440-64Thymosin Beta 15A (TMSB15A) is a Predictor of Chemotherapy Response in Triple-Negative Breast CancerThymosin Beta 15A (TMSB15A) is a Predictor of Chemotherapy Response in Triple-Negative Breast Cancer20121106Thymosin Beta 15A (TMSB15A) is a Predictor of Chemotherapy Response in Triple-Negative Breast CancerTreatment Response Biomarker Identified in Triple-Negative Breast CancerS Darb-Esfahani, R Kronenwett, G von Minckwitz, et alS Darb-Esfahani, R Kronenwett, G von Minckwitz, et al201210182012 Oct 18Br J CancerBr J CancerBreastEpidemiology and EtiologyTreatmentInvestigators validated thymosin beta 15A levels as predictive of response to neoadjuvant chemotherapy in patients with triple-negative breast cancer. Abstract Background: Biomarkers predictive of pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) of breast cancer are urgently needed.Methods: Using a training/validation approach for detection of predictive biomarkers in HER2-negative breast cancer, pre-therapeutic core biopsies from four independent cohorts were investigated: Gene array data were analysed in fresh frozen samples of two cohorts (n=86 and n=55). Quantitative reverse transcription polymerase chain reaction (qRT–PCR) was... Abstract Background: Biomarkers predictive of pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) of breast cancer are urgently needed. Methods: Using a training/validation approach for detection of predictive biomarkers in HER2-negative breast cancer, pre-therapeutic core biopsies from four independent cohorts wJournal Scans149 Br J Cancer, 2012 Oct 18, S Darb-Esfahani, et al Latest Approaches to Imaging Common Malignancies /journals/journal_scans/Advances_in_Oncologic_Imaging_Update_on_Five_Common_Cancers.html/journals/journal_scans/Advances_in_Oncologic_Imaging_Update_on_Five_Common_Cancers.htmltcm:8-284396-64Advances in Oncologic Imaging—Update on Five Common CancersAdvances in Oncologic Imaging—Update on Five Common Cancers20121105Advances in Oncologic Imaging—Update on Five Common CancersLatest Approaches to Imaging Common MalignanciesO Akin, SB Brennan, DD Dershaw, et alO Akin, SB Brennan, DD Dershaw, et al201210152012 Oct 15CA Cancer J ClinCA Cancer J ClinYesBreastColon and RectumHodgkin's LymphomaLungNon-Hodgkin's LymphomaProstateDiagnosis and StagingRecent progress in imaging technologies has provided opportunities for improved patient care. This article outlines relevant advances in breast, lung, prostate, and colorectal cancers and lymphoma. Abstract Imaging has become a pivotal component throughout a patient's encounter with cancer, from initial disease detection and characterization through treatment response assessment and posttreatment follow-up. Recent progress in imaging technology has presented new opportunities for improving clinical care. This article provides updates on the latest approaches to imaging of 5 common cancers: breast, lung, prostate, and colorectal cancers, and lymphoma. Abstract Imaging has become a pivotal component throughout a patient's encounter with cancer, from initial disease detection and characterization through treatment response assessment and posttreatment follow-up. Recent progress in imaging technology has presented new opportunities for improving clinical care. This article provides updatesJournal Scans149 CA Cancer J Clin, 2012 Oct 15, O Akin, et al
	Journal Scans: Review Epithelial–Mesenchymal Transition and Breast Cancer /journals/review_articles/YCTRV/Epithelial_Mesenchymal_Transition_and_Breast_Cancer_Role_Molecular_Mechanisms_and_Clinical_Impact.html/journals/review_articles/YCTRV/Epithelial_Mesenchymal_Transition_and_Breast_Cancer_Role_Molecular_Mechanisms_and_Clinical_Impact.htmltcm:8-282070-64Epithelial–Mesenchymal Transition and Breast Cancer: Role, Molecular Mechanisms and Clinical ImpactEpithelial–Mesenchymal Transition and Breast Cancer: Role, Molecular Mechanisms and Clinical Impact20120718Epithelial–Mesenchymal Transition and Breast Cancer: Role, Molecular Mechanisms and Clinical ImpactEpithelial–Mesenchymal Transition and Breast CancerC Foroni, M Broggini, D Generali, G DamiaC Foroni, M Broggini, D Generali, G DamiaYes201210012012 Oct 1Cancer Treat RevCancer Treat RevBreastEpidemiology and EtiologyAbstract Epithelial–mesenchymal transition (EMT) is defined by the loss of epithelial characteristics and the acquisition of a mesenchymal phenotype. In this process, cells acquire molecular alterations that facilitate dysfunctional cell–cell adhesive interactions and junctions. These processes may promote cancer cell progression and invasion into the surrounding microenvironment. Such transformation has implications in progression of breast carcinoma to metastasis, and increasing evidence supports the fact... Abstract Epithelial–mesenchymal transition (EMT) is defined by the loss of epithelial characteristics and the acquisition of a mesenchymal phenotype. In this process, cells acquire molecular alterations that facilitate dysfunctional cell–cell adhesive interactions and junctions. These processes may promote cancer cell progression and invasion into the surrounding microenvironment. Such transformation has implications in progression of breast carcinoma to metastasis, and increasinEditors ChoiceReview Articles38 Cancer Treat Rev, 2012 Oct 1, C Foroni, et al mTOR Inhibitors in Breast Cancer: A Systematic Review /journals/review_articles/GYNO/mTOR_Inhibitors_in_Breast_Cancer_A_Systematic_Review.html/journals/review_articles/GYNO/mTOR_Inhibitors_in_Breast_Cancer_A_Systematic_Review.htmltcm:8-283752-64mTOR Inhibitors in Breast Cancer: A Systematic ReviewmTOR Inhibitors in Breast Cancer: A Systematic Review20120926mTOR Inhibitors in Breast Cancer: A Systematic ReviewmTOR Inhibitors in Breast Cancer: A Systematic ReviewF Zagouri, TN Sergentanis, D Chrysikos, et alF Zagouri, TN Sergentanis, D Chrysikos, et alYes201209082012 Sept 8Gynecol OncolGynecol OncolBreastTreatmentAbstract PI3K/AKT/mTOR pathway is a crucial mediator of tumor progression. As the PI3K/Akt pathway is heavily deregulated in breast cancer, the application of mTOR inhibitors in breast cancer patients seems warranted. This is the first systematic review according to PRISMA guidelines to synthesize all available data of mTOR inhibitors in all subcategories of breast cancer. The search strategy retrieved 16 studies evaluating everolimus (1492 patients), seven studies examining temsirolimus (1245 patients),... Abstract PI3K/AKT/mTOR pathway is a crucial mediator of tumor progression. As the PI3K/Akt pathway is heavily deregulated in breast cancer, the application of mTOR inhibitors in breast cancer patients seems warranted. This is the first systematic review according to PRISMA guidelines to synthesize all available data of mTOR inhibitors in all subcategories of breast cancer. The search strategy retrieved 16 studies evaluating everolimus (1492 patients), seven studies examining temsiroEditors ChoiceReview Articles38 Gynecol Oncol, 2012 Sept 8, F Zagouri, et al Intensity-Modulated Radiotherapy in the Treatment of Breast Cancer /journals/review_articles/CLON/Intensity-Modulated_Radiotherapy_in_the_Treatment_of_Breast_Cancer.html/journals/review_articles/CLON/Intensity-Modulated_Radiotherapy_in_the_Treatment_of_Breast_Cancer.htmltcm:8-283579-64Intensity-Modulated Radiotherapy in the Treatment of Breast CancerIntensity-Modulated Radiotherapy in the Treatment of Breast Cancer20120913Intensity-Modulated Radiotherapy in the Treatment of Breast CancerIntensity-Modulated Radiotherapy in the Treatment of Breast CancerI Dayes, RB Rumble, J BowenI Dayes, RB Rumble, J BowenYes201209012012 Sept 1Clin OncolClin OncolBreastTreatmentAbstract Intensity-modulated radiotherapy (IMRT) is a newer method of radiotherapy that uses beams with multiple intensity levels for any single beam, allowing concave dose distributions and tighter margins than those possible using conventional radiotherapy. IMRT is ideal for treating complex treatment volumes and avoiding close proximity organs at risk that may be dose limiting and provides increased tumour control through an escalated dose and reduces normal tissue complications through organ at risk sparing.... Abstract Intensity-modulated radiotherapy (IMRT) is a newer method of radiotherapy that uses beams with multiple intensity levels for any single beam, allowing concave dose distributions and tighter margins than those possible using conventional radiotherapy. IMRT is ideal for treating complex treatment volumes and avoiding close proximity organs at risk that may be dose limiting and provides increased tumour control through an escalated dose and reduces normal tissue compliEditors ChoiceReview Articles38 Clin Oncol, 2012 Sept 1, I Dayes, et al
	Videos Newer, More Costly Drugs No Better Than Paclitaxel /video/ASCO_2012/Newer_More_Costly_Drugs_No_Better_Than_Paclitaxel.html/video/ASCO_2012/Newer_More_Costly_Drugs_No_Better_Than_Paclitaxel.htmltcm:8-280638-64Newer, More Costly Drugs No Better Than PaclitaxelNewer, More Costly Drugs No Better Than Paclitaxel20120611Newer, More Costly Drugs No Better Than PaclitaxelNewer, More Costly Drugs No Better Than Paclitaxel201206032012 Jun 3IMNG Medical MediaIMNG Medical Media/Images/Hope_Rugo_tcm8-280633.jpgBreastTreatmentASCO 2012A phase III randomized trial found that weekly administration of either of two newer and significantly more costly agents, nanoparticle albumin bound ("nab") paclitaxel (Abraxane) and ixabepilone (Ixempra), was not superior to standard weekly dosing of paclitaxel as first-line therapy for locally advanced or metastatic breast cancer. Furthermore, paclitaxel appears to offer better progression-free survival (PFS) than ixabepilone and fewer toxicities than nab-paclitaxel in this setting. /Images/Hope_Rugo_tcm8-280633.jpg See related videos to: ASCO 2012 Copyright © 2012 International Medical News Group Subscribe Now » Videos13 IMNG Medical Media, 2012 Jun 3,

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