John Babcook

P504S: a new molecular marker for the detection of prostate carcinoma.

* ون ي ،لوئسم هدنس نسح ناديم ،نارهت ،انيس ناتسراميب ،دابآ يژولوتاپ شخب نفلت : 9 66701041 email: ahmadise@tums.ac.ir فده و هنيمز : رب ديكات دوز فشك طرس ماگنه ب تاتسورپ نا ه كمك ارت يفارگونوسارتلوا سن لاـتكر ،ينزوـس يسـپويب و تسيژولوتاپ ار اه ناطرس صيخشت لضعم اب تـسا هدومن هجاوم كچوك ياه . ارـيخا ̋ زا ركراـم P504S صيخشـت تـهج يسپويب رد ناطرس يعطق تسا هدش هدافتسا كچوك ياه . يسررب شور : گنر ركرام يزيمآ P504S يارب 70 سپويب هنومن ي و تاتسورپ ينزوس شش زر هنومن ك هك ارجم قيرط زا نويس يگمه نوناك يواح ياه كوكشم ) پيتآ ـ ي ك ( و دـندوب زـين 40 هنومن تاتسورپ يعطق ناطرس ، لماش تشه لولس ياراد هنومن فك ياه دولآ (foamy) ب ه دمآ لمع . هتفاي اـه : 36 زا هـنومن 40 ،يعطق ناطرس يسپويب زا يتاجرد گنر يارب يريذپ P504S دـنداد ناشن ) تيساسـح 90 (% ؛ ود و كـچوك ناطرـس ود لولس اب ناطرس فك ياه گنر دقاف دولآ دندوب يريذپ . عومجم زا 76 ،كوكشم دروم 18 ـ ب دروم ه لـخاد يزلاپوـئن ناوـنع يپا لااب هجرد يلايلت (HGPIN) دش هتخانش دن هك 16 دروم اهنآ گنر دنداد ناشن رشتنم طسوتم يريذپ . زا 58 دروم يقاب هدـنام ياراد يلورپ نويسارف كچوك ددغ آ يت كيپ 14 ًايوق دروم ب ه ن ف دوب ناطرس ع هك راهچ گـنر دـقاف اـهنآ دروـم يريذـپ P504S دندوب . رد نيب 44 پيتآ دروم ي ك ب ه عفن شوخ ميخ ي ، 14 پيتآ يموندآ يزلاپرپيه دروم ي ك اب ود گنر دروم فيعـض يريذـپ يعضوم و ود ب يپيتآ دروم ه ب يباتوترپ لابند ا كي گنر دروم و دش هدهاشم يعضوم يريذپ 28 رـگيد هـنومن P504S يـفنم دندوب . هجيتن يريگ : تيساسح P504S يم روصت ًلابق هچنآ زا تاتسورپ ناطرس فشك يارب نيياپ دش تـسا رت . يـفنم يـّقلت ندش ناطرس نكمم كچوك ياه ا ب تس ه گـنر ينوگمهاـن ليلد دـشاب يريذـپ . نويـسارفيلورپ رد كـچوك ددـغ تآ پي ـ ي ،ك گنر رشتنم و تبثم يريذپ P504S گنر مدع يلو تسا ناطرس صيخشت يايوگ ًايوق يـمن در ارنآ يريذپ دـنك . تيساسـحThe ability to diagnose prostate carcinoma would be improved by the detection of a tumor-associated antigen. P504S, a cytoplasmic protein, was recently identified by cDNA library subtraction in conjunction with high throughput microarray screening from prostate carcinoma. The aim of this study was to establish the pattern of expression of P504S in prostate carcinoma and benign prostatic tissue. A total of 207 cases, including 137 cases of prostate carcinoma and 70 cases of benign prostate, from prostatectomies (n = 77), prostate needle biopsies (n = 112), and transurethral prostate resections (n = 18) were examined by immunocytochemistry for P504S. P504S showed strong cytoplasmic granular staining in 100% of prostate carcinomas regardless of Gleason scores and diffuse (>75% of tumor) staining in 92% of cases. In contrast, 171 of 194 (88%) of benign prostates, including 56 of 67 (84%) benign prostate cases and 115 of 127 (91%) cases of benign glands adjacent to cancers were negative for P504S. The remainders of benign prostates were focally and weakly positive for P504S. The staining pattern of these normal glands was different and easily distinguishable from that observed in prostate carcinoma. Expression of P504S was not found in basal cell hyperplasia, urothelial cells/metaplasia and small atrophic glands that may mimic prostate carcinoma. Our findings indicate that P504S is a highly sensitive and specific positive marker for prostate carcinoma.

Detection of Mammaglobin in the Sera of Patients with Breast Cancer

Current procedures for the diagnosis of breast cancer are cumbersome and invasive, making detection of this disease difficult. A rapid screening test for early detection of breast cancer would allow for better management of this deadly disease. In this report, we show that, with the exception of the skin, mammaglobin mRNA is specifically expressed in mammary tissue and commonly overexpressed in breast cancer. Mammaglobin is not expressed in other types of cancer including colon, lung, ovarian, and prostate cancer. Breast-specific expression of mammaglobin protein was shown using immunohistochemical methods. Mammaglobin is secreted from both established breast cancer cell lines and primary breast carcinoma cells cultured in vitro. Using a monoclonal antibody-based assay for monitoring the presence of mammaglobin in serum, elevated levels of mammaglobin were detected in sera of patients with breast cancer, but not in healthy women. Thus, mammaglobin, which is overexpressed and secreted from breast carcinoma cells, is detectable in sera of patients with breast cancer and may provide a rapid screening test for the diagnosis and management of breast cancer.

Generation and characterization of human monoclonal neutralizing antibodies with distinct binding and sequence features against SARS coronavirus using XenoMouse.

Abstract Passive therapy with neutralizing human monoclonal antibodies (mAbs) could be an effective therapy against severe acute respiratory syndrome coronavirus (SARS-CoV). Utilizing the human immunoglobulin transgenic mouse, XenoMouse®, we produced fully human SARS-CoV spike (S) protein specific antibodies. Antibodies were examined for reactivity against a recombinant S1 protein, to which 200 antibodies reacted. Twenty-seven antibodies neutralized 200TCID50 SARS-CoV (Urbani). Additionally, 57 neutralizing antibodies were found that are likely specific to S2. Mapping of the binding region was achieved with several S1 recombinant proteins. Most S1 reactive neutralizing mAbs bound to the RBD, aa 318–510. However, two S1 specific mAbs reacted with a domain upstream of the RBD between aa 12 and 261. Immunoglobulin gene sequence analyses suggested at least 8 different binding specificities. Unique human mAbs could be used as a cocktail that would simultaneously target several neutralizing epitopes and prevent emergence of escape mutants.

Human monoclonal antibodies to SARS-coronavirus inhibit infection by different mechanisms.

Abstract SARS-CoV causes an acute infection making targeted passive immunotherapy an attractive treatment strategy. We previously generated human mAbs specific to the S1 region of SARS-CoV S protein. These mAbs bind epitopes within the receptor binding domain (RBD) or upstream of the RBD. We show that mAbs recognizing epitopes within the RBD inhibit infection by preventing viral attachment to the cellular receptor. One mAb binds upstream of the RBD and prevents viral entry by inhibiting a post-binding event. Evaluation of several mAbs demonstrated varying ability of the mAbs to select escape mutants when used individually. However, a mixture of antibodies could effectively neutralize a range of mutant viruses. These data strongly suggest that a mixture containing antibodies recognizing distinct regions and targeting more than one step in viral entry is likely to be more effective in neutralizing the virus and suppressing the generation of escape mutants, and thus potentially constitute a highly effective passive immunotherapy.

Interleukin‐21 Receptor Blockade Inhibits Secondary Humoral Responses and Halts the Progression of Preestablished Disease in the (NZB × NZW)F1 Systemic Lupus Erythematosus Model

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that is driven in part by chronic B and T lymphocyte hyperresponsiveness to self antigens. A deficiency of interleukin‐21 (IL‐21) or IL‐21 receptor (IL‐21R) in mice dramatically reduces inflammation and B and T cell activation in models of autoimmunity, including SLE. However, whether IL‐21 is essential for the maintenance and amplification of preestablished inflammation has not been widely examined in various animal models. The purpose of this study was to examine the impact of novel mouse IL‐21R neutralizing antibodies on recall responses to antigen challenge and on disease progression in the (NZB × NZW)F1 (NZB/NZW) mouse model of SLE.