Abbass Ezz's Review For Mac
In this study, the authors examined a large and well characterized series of invasive breast carcinoma (n = 1944) with a long‐term clinical follow‐up (median, 56 months) by using tissue microarray. The series were also stained with concurrent immunohistochemical prognostic panels (estrogen receptor, progesterone receptor, HER‐2, androgen receptor, epidermal growth factor receptor (EGFR), P‐cadherin, E‐cadherin, and basal (CK5/6, CK14), and p53), to characterize this specific subgroup of breast cancer and to identify prognostic markers that can identify tumors with more aggressive behavior. Of informative cases, 16.3% were of the triple‐negative phenotype. The majority of these tumors were grade 3, ductal/no‐specific‐type carcinomas. There were positive associations with larger size, pushing margins, poorer Nottingham Prognostic Index, development of recurrence and distant metastasis, and poorer outcome. In addition, associations were found with loss of expression of androgen receptor and E‐cadherin, and positive expression of basal cytokeratins (basal phenotype), P‐cadherin, p53, and EGFR. In all tumors, tumor size, lymph node stage, and androgen receptor were the most useful prognostic markers.
In the lymph node‐positive subgroup, both size and androgen receptor retained their prognostic significance. However, in the lymph node‐negative tumors, basal phenotype was the sole prognostic marker identified in this subgroup.
Other parameters including age, histological grade, tumor size, vascular invasion or other biomarkers included in the current study were not significant. Human breast carcinomas represent a heterogeneous group of tumors that are diverse in behavior, outcome, and response to therapy. Although its incidence is still high, the overall mortality due to breast cancer has decreased, attributed in part to early application of various treatments. To reduce mortality from breast cancer further, there is a desire to examine and characterize tumors of poor prognosis, to predict their biology, to ensure adequate therapy, and to improve patients' outcome. There is also a need to develop additional forms of systemic treatment effective in those tumors that fail to express known targets such as estrogen receptor, progesterone receptor, or C‐erbB‐2 (HER2). Emerging data demonstrate that stratification of tumors by gene‐expression profiles and other techniques - divides breast cancer into a mixture of at least 2 main types with 5 subtypes, according to hormone receptor (HR) expression (negative or positive) and/or epithelial cellular origin (basal or luminal), that have clinical implication.
The hormone receptor‐negative group has 3 subtypes: 1 with HER2 overexpression, 1 normal‐like, and 1 basal subtype with positive epidermal growth factor receptor (EGFR), absent HR (estrogen receptor and progesterone receptor), and absent HER2 expression (triple‐negative subtype). Previous DNA microarray and immunohistochemical (IHC) analyses have shown that 80% to 90% of triple‐negative tumors are basal‐like and have a clinical behavior similar to basal‐like behavior. In addition, mammary stem cell studies have reported that this triple‐negative phenotype is a feature of mouse mammary stem cells, which also express EGFR and other stem cell markers. HR‐negative tumors are more likely to be poorly differentiated, of higher histological grade, associated with a higher recurrence rate and a decreased overall survival, and unresponsive to antiestrogens. However, a significant proportion of a small subset of invasive cancers, eg, adenoid cystic carcinoma and secretory carcinoma, are HR‐negative., These tumors have an excellent prognosis with minimal regional recurrence. In addition, not all poorly differentiated, HR‐negative tumors behave poorly. Medullary‐like cancers are reported in some series to have a relatively better prognosis than expected.
All these features point toward the heterogeneous nature of a HR‐negative subgroup of invasive breast cancers and may indicate the presence of more aggressive subgroups within these tumor types that can be benefit from an aggressive therapy. HER2 is a major target for the development of new cancer therapies and is similar to the estrogen receptor, which guides hormone therapy.
Its greatest value as a predictive marker lies in the prediction of response to therapies that target HER2, such as trastuzumab (Herceptin). Although HER2‐negative disease has a more favorable prognosis than HER2‐positive disease, it lacks the benefit of using these targeted therapies.
Previous studies have reported that HER2 status usually shows an inverse association with HR expression. In this study, we investigated the high‐risk group of breast cancer with the triple‐negative phenotype (estrogen receptor‐negative, progesterone receptor‐negative, and HER2‐negative) that lacks the benefit of specific therapy that targets these proteins to characterize and identify additional prognostic markers that can identify tumors with more aggressive behavior. MATERIALS AND METHODS This study investigated a consecutive series of 1944 cases of primary operable invasive breast carcinoma obtained from Nottingham Tenovus Primary Breast Carcinoma Series from patients presenting between 1986 and 1998. This is a well‐characterized series of primary breast carcinoma with a long‐term follow‐up that has been treated in a uniform way and previously used to study a wide range of biomarkers., Patient's clinical history and tumor characteristics were assessed in a uniform fashion. Information on therapy, local, regional, and distant recurrence, and survival was maintained on a prospective basis.
The Nottingham Prognostic Index (NPI) was calculated by using the following equation: NPI = 0.2 tumor size (cm) + grade (1–3) + lymph node score (1–3). This index predicts the survival of patients with invasive breast cancer, and it can define 3 subsets of patients with different chances of dying from breast cancer; good (≤3.4), moderate (3.41–5.4), and poor (5.4) prognostic groups. The disease‐free interval (DFI) was defined as the interval (in months) from the date of the primary surgery to the first locoregional recurrence or distant metastasis. The overall survival (OS) was the time, in months, from the date of the primary surgery to the time of breast cancer‐related death. The median OS of the whole series was 73 months, and the median time of event‐free survival was 66 months (range, 1 to 206 months). Recurrence occurred in 335 (18.8%) cases (184 cases, 16.4%, in the lymph node‐negative and 150, 23%, in the lymph node‐positive group), distant metastases in 203 (11.4%) cases, and 176 (9.9%) patients died from breast cancer during the period of follow‐up (75 cases 6.7% in the lymph node‐negative and 100 15.4% in the lymph node‐positive group).
The Nottingham Prognostic Index ranged from 2–8.6 (mean, 4.2). Hormonal therapy was given to 536 (35.8%) patients and chemotherapy to 261 (17.4%) patients. Breast cancer tissue microarrays were prepared and immunohistochemically stained for estrogen receptor, progesterone receptor, HER2, EGFR, androgen receptor, p53, P‐cadherin, E‐cadherin, and basal cytokeratins (CK5/6 and CK14) (Table ) as previously described., - Positive and negative controls for each marker were used according to the supplier's data sheet (Zymed Laboratories, Inc., San Francisco, CA; DakoCytomation Ltd., Cambridge, UK; Launch Diagnostics Ltd., Kent, UK; BD Biosciences, Oxford, UK; Novocastra Vision Biosystems (Europe) Ltd., Newcastle Upon Tyne, UK). Two cores were evaluated from each tumor and only staining of the invasive malignant cells was considered.
Each core was scored individually, and the mean of the 2 readings was calculated. Immunohistochemical scoring was performed in a blind fashion. Antibody, clone Dilution Source Pretreatment Cutoff values ER clone 1D5 1:80 DakoCytomation Microwave 0% (negative) PR clone PgR 636 1:100 DakoCytomation 0% (negative) HER‐2 (cerbB‐2) 1:250 DakoCytomation None 5% (positive) CK5/6cloneD5/16134 1:100 Boehringer Biochemica Microwave ≥10% (positive) CK 14 clone LL002 1:100 EGFR clone EGFR.113 1:10 Novocastra Microwave ≥10% (positive) Anti E‐cadherin clone HECD‐1 1:100 Zymed Laboratories Microwave ≥100 (H‐score; median) Anti P‐cadherin clone 56 1/200 BD Biosciences ≥5% (positive). Statistical Analysis Statistical analysis was performed using SPSS 13.0 statistical software (SPSS Inc, Chicago, Ill). We examined the association between triple‐negative phenotype and other clinicopathologic variables, and the significance of different prognostic markers using chi‐squared test, and chi‐squared test for trend as appropriate.
The association with survival was analyzed initially by Kaplan‐Meier plot and log‐rank test and also with Cox regression analysis to adjust for other prognostic indicators. A P‐value of 100 (E‐cadherin) were considered positive. This research was approved by the Nottingham Research Ethics Committee 2 under the title of “Development of a Molecular Genetic Classification of Breast Cancer.”. RESULTS In the current study, 1726 cases of invasive breast carcinomas were informative for the 3 markers (estrogen receptor, progesterone receptor, and HER2). Of these informative cases, 282 (16.3%) showed a triple‐negative phenotype (estrogen receptor‐negative, progesterone receptor‐negative, and HER2‐negative, regardless of the expression of EGFR or basal cytokeratins) and formed the basis of this study. The patients had a median age of 49.9 years (range, 25–70 years). The majority (80.9%) of tumors were ductal carcinoma of no special type (duct/NST) (compared with 56% in the whole breast carcinoma series; 1944 cases) and 3.2% were of metaplastic and salivary gland‐like carcinomas (compared with 0.7% in the whole breast carcinoma series).
The Nottingham Prognostic Index in these cases ranged from 2.3–7.6 (mean, 4.8). Fifty‐three (23%) cases received hormonal therapy and 106 (55%) received chemotherapy. The median overall survival was 54 months, and the median time of event‐free survival was 49 months (range, 1 to 146 months). Table shows the main features of triple‐negative tumors compared with nontriple‐negative tumors concerning different clinicopathological variables and biomarkers used in the current study.
Triple‐negative phenotype was associated with larger size, grade 3 tumors, pushing margin (χ 2 = 6.7, P =.009), development of recurrence and distant metastasis, and poorer Nottingham Prognostic Index (χ 2 = 112.6, P. Variables Total no. (%) Triple negative no. (%) Non‐triple negative no. (%) χ 2 ( P value) Grade 236 (1.5cm 1124 222 902 Definite VI 727 (41) 106 (37) 621 (44) 3.3 (0.07) DM 203 (11) 47 (17) 156 (10) 10 (.001) Recurrence 335 (19) 69 (25) 266 (17.7) 8.2 (.004) No.
Of breast cancer deaths 176 (10) 47 (17) 129 (8.6) 18.7 (. LN indicates lymph node; VI, vascular invasion; DM, distant metastasis; AR, androgen receptor; BP, basal phenotype.
To study the response of these tumors to adjuvant treatment, we stratified the informative breast carcinoma series into matching subgroups according to different grades, sizes, and the Nottingham Prognostic Index. We found that in the poor Nottingham Prognostic Index group (all were lymph node‐positive, grade 3 tumors, and sized ≥1.5 cm; 227 cases after exclusion of 22 cases of grade 2 or size.
It's certainly possible to develop on a Windows machine, in fact my first application was exclusively developed on the old Dell Precision I had at the time:) There are three routes;. Install (aka iATKOS / Kalyway) on a second partition/disk and dual boot. Run Mac OS X Server under VMWare (Mac OS X 10.7 (Lion) onwards, read the update below).
Use Delphi XE4 and the macincloud service. This is a commercial tool set, but the component and lib support is growing. The first route requires modifying (or using a pre-modified) image of Leopard that can be installed on a regular PC. This is not as hard as you would think, although your success/effort ratio will depend upon how closely the hardware in your PC matches that in Mac hardware - e.g. If you're running a Core 2 Duo on an Intel Motherboard, with a NVidia graphics card you are laughing.
If you're running an AMD machine or something without SSE3 it gets a little more involved. If you purchase (or already own) a version of Leopard then this is a gray area since the Leopard EULA states you may only run it on an 'Apple Labeled' machine. As many point out if you stick an Apple sticker on your PC you're probably covered. The second option is the more costly. The EULA for the workstation version of Leopard prevents it from being run under emulation and as a result there's no support in VMWare for this. Leopard server however CAN be run under emulation and can be used for desktop purposes. Leopard server and VMWare are expensive however.
If you're interested in option 1) I would suggest starting at and reading the OSx86 sections. I do think you should consider whether the time you will invest is going to be worth the money you will save though. It was for me because I enjoy tinkering with this type of stuff and I started during the early iPhone betas, months before their App Store became available.
Alternatively you could pickup a low-spec Mac Mini from eBay. You don't need much horse power to run the SDK and you can always sell it on later if you decide to stop development or buy a better Mac. Update: You cannot create a Mac OS X Client virtual machine for OS X 10.6 and earlier.
Apple does not allow these Client OSes to be virtualized. With Mac OS X 10.7 (Lion) onwards, Apple has changed their licensing agreement in regards to virtualization.
Is now my top vote. Purchased by Microsoft and built directly into Visual Studio now and being able to use C# and with all the updates and features they are adding, you can do everything on Windows, even compile, build and initiate deployment.
You only need a Mac Mini to act as the deployment server, but you never need to write any code on it. For games, is my top choice. The editor is free up to 100K annual revenue (perfect for indie). Unity 5+ is fully unlocked as well, even the free version.
Abbass Ezz's Review For Mac 2017
Unity supports iOS, Android and most other platforms. For iOS and MAC, simply get the cheapest MAC Mini you can find to do the build, but all the development can be done on Windows. Other options: also works, but I have found it isn't quite as nice for gaming, but it's pretty decent for regular GUI applications. Again, you'll need a Mac to sign and test your application and be in compliance with Apple's terms of use. Most of 'so called Windows solutions for iOS development without Mac' require Mac at the end just to sign and send to app store.
I checked a few, not all though (who has the time?) At the end it's just too much trouble to learn 'their super special easy way to program iOS without Objective-C', they have lots of bugs. Really the goal they are setting is unachievable in my view. Also a lot of time they make you use Objective-C equivalent statements simply in another language. They kind of look the same but there are always subtle differences that you have to learn on top of obj-c. Which also makes even less sense, because now instead of learning less you have to learn more.
So where is the gain? Also they cost a lot, because they are very hard to develop. Many lack any debugging abilities whatsoever.
In my honest opinion, if you are a hard-core iOS developer then for sure buy the best Mac and learn objective-c. It's expensive and takes time, but if it's your path, it's worth it. For an occasional use, it's just easier to rent a remote Mac service, like. The SDK is only available on OS X, forcing you to use a mac. If you don't want to purchase a mac you can either run OS X on a virtual machine on your windows box, or you can install OS X on your PC. In my experience the virtual machine solution is unusably slow (on a core2 duo laptop with 2G ram). If you feel like trying it search for the torrent.
It's probably not worthwhile. The other option is to install OS X on your PC, commonly referred to as a hackintosh. Hackintoshes work quite well - my friend just sold his mac because his Dell quad core hackintosh was actually much faster than the apple hardware (and cost about 1/3). You can find lots of articles on how to do this; here's one on how to install on a Dell Inspirion 1525 laptop: Of course both of these options are likely counter to some licensing scheme, so proceed at your own risk. You don't need to own a Mac nor do you need to learn Objective-C.
You can develop in different environments and compile into Objective-C later on. This article one of our developers wrote gives a pretty comprehensive walk through on installing OS X Snow Leopard on Windows using iBoot, then installing Vmware (with instructions), then getting your iPhone dev environment going. And a few extra juicy things. Super helpful for me. Hope that helps. It uses Phonegap so you can develop on multiple smart phone platforms at once.
Of course, you can write Objective-C code in notepad or other programs and then move it to a Mac to compile. But seriously, it depends on whether you are developing official applications to put in App Store or developing applications for jailbroken iPhone. To write official applications, Apple iPhone SDK which requires an Intel Mac seems to be the only practical way.
However, there is an unofficial toolchain to write applications for jailbroken iPhones. You can run it on Linux and Windows (using Cygwin).
If you want it to be legitimate, you have two options, cloud based Mac solutions or cross-platform development tools. You may consider the hackintosh approach or virtual machines if you don't care about legal stuff. If you have a decent PC, running a virtual machine would be the easiest way to go.
Abbass Ezz's Review For Macbook Pro
You may never know which hardware will have driver issues on a hackintosh. I've tried all these approaches and they all have pros and cons, but for the second group, I feel kind of guilty. I develop apps to make a living and I wouldn't want to rip off someone else for it. If you are making a small project, cloud based Macs may prove useful. Rent it for a short time, develop your project and off you go.
Don't bother learning anything new. However, if your project is getting big, cross-platform frameworks seem to be the only alternative. The critical thing is that you need to choose wisely. There are so many hybrid frameworks, but what they do can be summarized in one sentence as 'diplaying web pages in an app wrapper' and developers' negative experience with hybrid frameworks also affects native frameworks. I tried three of these (Titanium, Smartface and Xamarin) and they all claim to produce 'real native output' and in my opinion their claims are correct. You need to test and see it yoursrlf, it's not easy to describe the native feeling. In a previous comment, it was indicated that it takes some effort to learn these platforms, but once you get to know them, you can develop not just iOS applications but Android applications as well, all with the common code base.
And of course, they are much cheaper than a cloud Mac. Some of them are even free. You would need a Mac only for store submission. If you know JavaScript, try Titanium and Smartface and if you know C#, try Xamarin. Just note that for the device simuator, Titanium is dependent on a Mac, but Smartface has a simulator app for Windows development and it works better than I expected.
On the other hand, Xamarin requires a Mac in your network.