The effects of metallic nanoparticles as cytotoxicity or antibacterial activity are widely known. It is also obvious that ultrasound is one of the most widely used therapeutic modalities in medicine. The effect of application of therapeutical ultrasonic field in the presence of metallic nanoparticles AgCu &#x3C;100&#x2009;nm modified by phenanthroline or polyvinyl alcohol was examined on human ovarian carcinoma cells A2780. Metallic nanoparticles were characterized by electron microscopy and by measuring of zeta potential. The cell viability was tested by MTT test. The experimental results indicate a significant decrease of cell viability, which was affected by a combined action of ultrasound field and AgCu nanoparticles. The maximum decrease of cells viability was observed for nanoparticles modified by phenanthroline. The effect of metallic nanoparticles on human cell in presence of ultrasound exposure was found&#x2014;a potential health risk or medical advantage of targeted therapy in the future.

Vladan Bernard

Ond&#x159;ej Zoba&#x10d;

Ji&#x159;&#xed; Sopou&#x161;ek

Vojt&#x11b;ch Mornstein

AgCu Bimetallic Nanoparticles under Effect of Low Intensity Ultrasound: The Cell Viability Study In Vitro

<i>Aim.</i> To investigate whether breast cancer incidence increases with increasing latitude in mainland Australian women. <i>Methods.</i> A cross-sectional study of female breast cancer and cutaneous melanoma incidence 2002&#x2013;2006 by 5-year age group and local government area. Latitude, Accessibility/Remoteness Index of Australia (ARIA), and Index of Relative Socioeconomic Disadvantage (IRSD) were assigned to local government areas. Latitude was grouped into bands (&#x2264;27&#xb0;S; &#x3e;27&#x2013;30&#xb0;S; &#x3e;30&#x2013;33&#xb0;S; &#x3e;33&#x2013;36&#xb0;S, and &#x3e;36&#xb0;S), and IRSD was divided into quintiles and ARIA into four categories. Breast cancer rates were age standardized using the direct method. The joint effects of latitude, age, IRSD, and ARIA on incidence of breast cancer and cutaneous melanoma were assessed using multiple logistic regressions. <i>Results.</i> At latitudes south of 30&#xb0;S, rates of breast cancer were over double that north of 27&#xb0;S (76.4 versus 160.2&#x2013;176.5). Age-adjusted odds ratios of breast cancer were increased in all latitudes south of 30&#xb0;S compared with north of 27&#xb0;S within each IRSD and ARIA category (all <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.6617603pt" id="M1" height="9.65971pt" version="1.1" viewBox="-0.0498162 -8.99795 53.2534 9.65971" width="53.2534pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><path id="g113-81" d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z"/></g><g transform="matrix(.0135,0,0,-0.0135,12.15,0)"><path id="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g><g transform="matrix(.0135,0,0,-0.0135,23.887,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.0135,0,0,-0.0135,30.39,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.0135,0,0,-0.0135,33.48,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,39.983,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,46.486,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g></svg>). After adjusting for age, IRSD, and ARIA, the odds ratio of breast cancer south of 30&#xb0;S was 1.92 (95&#x25; CI 1.84&#x2013;2.09; <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.6617603pt" id="M2" height="9.65971pt" version="1.1" viewBox="-0.0498162 -8.99795 53.2534 9.65971" width="53.2534pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.0135,0,0,-0.0135,12.15,0)"><use xlink:href="#g117-91"/></g><g transform="matrix(.0135,0,0,-0.0135,23.887,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,30.39,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.0135,0,0,-0.0135,33.48,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,39.983,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,46.486,0)"><use xlink:href="#g113-50"/></g></svg>), whereas cutaneous melanoma was 0.65 (95&#x25; CI 0.61&#x2013;0.68; <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.6617603pt" id="M3" height="9.65971pt" version="1.1" viewBox="-0.0498162 -8.99795 53.2534 9.65971" width="53.2534pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.0135,0,0,-0.0135,12.15,0)"><use xlink:href="#g117-91"/></g><g transform="matrix(.0135,0,0,-0.0135,23.887,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,30.39,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.0135,0,0,-0.0135,33.48,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,39.983,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,46.486,0)"><use xlink:href="#g113-50"/></g></svg>) times north of 30&#xb0;S. <i>Discussion.</i> Increasing latitude is positively associated with breast cancer and negatively associated with cutaneous melanoma incidence. These findings support suggestions that increased risk of breast cancer might be explained by lower ultraviolet radiation-induced vitamin D synthesis.

Kellie Bilinski

Karen Byth

John Boyages

Association between Latitude and Breast Cancer Incidence in Mainland Australian Women

We conducted this prospective study which included 28 de novo CD20-positive DLBCL patients to assess the clinical outcome, treatment response, and hepatic toxicity in DLBCL patients who received rituximab-CHOP as a first line treatment in relation to HCV infection status. We included 7 patients with positive HCV infection (group A) and 21 patients with negative HCV infection (group B). HCV infection was not a significant risk factor for prognosis (1-year event-free survival rates, 71.4&#x25; versus 81&#x25;, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2129908pt" id="M1" height="9.21094pt" version="1.1" viewBox="-0.0498162 -8.99795 46.7259 9.21094" width="46.7259pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><path id="g113-81" d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z"/></g><g transform="matrix(.0135,0,0,-0.0135,12.15,0)"><path id="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g><g transform="matrix(.0135,0,0,-0.0135,23.887,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.0135,0,0,-0.0135,30.39,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.0135,0,0,-0.0135,33.48,0)"><path id="g113-54" d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"/></g><g transform="matrix(.0135,0,0,-0.0135,39.983,0)"><path id="g113-52" d="M285 378C315 398 338 416 353 432C373 451 384 474 384 503C384 579 325 635 236 635H235C182 635 136 610 108 579L65 516L85 496C110 533 150 575 205 575C258 575 300 543 300 481C300 407 232 369 141 339L147 310C163 315 188 321 211 321C268 321 338 284 338 192C338 94 288 40 217 40C160 40 119 68 93 91C85 98 77 97 69 91C60 84 47 71 46 58C44 46 48 35 62 22C75 10 116 -12 162 -12C234 -12 424 62 424 224C424 297 373 359 285 376V378Z"/></g></svg>; overall survival rates, 85.7&#x25; versus 90.5&#x25;, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2129908pt" id="M2" height="9.21094pt" version="1.1" viewBox="-0.0498162 -8.99795 46.7259 9.21094" width="46.7259pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.0135,0,0,-0.0135,12.15,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.0135,0,0,-0.0135,23.887,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,30.39,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.0135,0,0,-0.0135,33.48,0)"><path id="g113-56" d="M447 623H65C61 580 56 530 47 475H76C100 541 106 550 172 550H388C308 376 196 170 91 -1L98 -12L172 -2C268 204 360 408 455 611L447 623Z"/></g><g transform="matrix(.0135,0,0,-0.0135,39.985,0)"><path id="g113-51" d="M412 140C382 77 369 73 315 73H129L270 222C362 320 402 379 402 466C402 571 322 635 234 635C177 635 130 609 99 576L42 495L64 475C90 514 133 568 201 568C274 568 318 519 318 435C318 349 255 267 193 193C144 135 87 78 32 23V0H405C417 45 427 89 440 131L412 140Z"/></g></svg>, for groups A and B, resp.). CR rate was 71.4&#x25; (5/7) in group A and 76.2&#x25; (16/21) in group B (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2129908pt" id="M3" height="9.21094pt" version="1.1" viewBox="-0.0498162 -8.99795 40.1984 9.21094" width="40.1984pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.0135,0,0,-0.0135,12.15,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.0135,0,0,-0.0135,23.887,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,30.39,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.0135,0,0,-0.0135,33.48,0)"><path id="g113-57" d="M249 635C141 635 70 555 70 471C70 401 114 353 179 316C143 294 106 267 90 252C68 231 45 202 45 157C45 50 130 -12 237 -12C322 -12 435 52 435 169C435 256 372 304 303 343C349 374 375 398 383 407C401 429 411 458 411 487C411 569 344 635 249 635ZM238 603C285 603 337 567 337 482C337 422 310 385 276 358C205 393 145 426 145 500C145 552 179 603 238 603ZM248 20C183 20 125 70 125 163C125 218 158 268 206 300C284 261 355 217 355 143C355 66 308 20 248 20Z"/></g></svg>). Of the 7 patients who were HCV positive, 2 (28.6&#x25;) had enzyme flare (grade 2), compared with 1 of the 21 (4.8&#x25;) patients who were HCV negative (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2129908pt" id="M4" height="9.21094pt" version="1.1" viewBox="-0.0498162 -8.99795 46.7259 9.21094" width="46.7259pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.0135,0,0,-0.0135,12.15,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.0135,0,0,-0.0135,23.887,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,30.39,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.0135,0,0,-0.0135,33.48,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g><g transform="matrix(.0135,0,0,-0.0135,39.983,0)"><use xlink:href="#g113-54"/></g></svg>). Two (28.6&#x25;) of the 7 positive HCV infection patients had viral reactivation (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-1.16493pt" id="M5" height="9.26535pt" version="1.1" viewBox="-0.0498162 -8.10042 8.08224 9.26535" width="8.08224pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><path id="g117-94" d="M531 285V335L57 550V494L473 310L57 127V71L531 285ZM531 -40V10H57V-40H531Z"/></g></svg>1&#x2009;log<sub>10</sub>&#x2009;IU/mL increase in the viral load).  No patient required discontinuation of immunochemotherapy owing to hepatotoxicity in either group. In conclusion, HCV infection might not influence the clinical course in DLBCL patients who receive rituximab-CHOP. Close monitoring of hepatic function and viral load is recommended.

Fouad Abu-Taleb

Rasha Haggag

Yasser Elnaggar

Ahmed Embaby

Impact of Immunochemotherapy-Related Hepatic Toxicity on the Outcome of HCV-Positive Diffuse Large B-Cell Lymphoma Patients

This study is done to evaluate the effect of spleen tyrosine kinase inhibitor (BAY 61-3606), cyclin-dependent kinase inhibitor (CDKi), and sodium butyrate (Na-Bu) on the level and phosphorylation of p53 protein and its binding to murine double minute 2 (MDM2) homologue in human vestibular schwannomas (VS). Primary cultures of the tumor tissues were treated individually with optimum concentrations of these small molecules <i>in vitro</i>. The results indicate modulation of p53 protein status and its binding ability to MDM2 in treated samples as compared to the untreated control. The three individual treatments reduced the level of total p53 protein. These treatments also decreased Ser392 and Ser15 phosphorylated p53 in tumor samples of young patients and Ser315 phosphorylated p53 in old patients. Basal level of Thr55 phosphorylated p53 protein was present in all VS samples and it remained unchanged after treatments. The p53 protein from untreated VS samples showed reduced affinity to MDM2 binding <i>in vitro</i> and it increased significantly after treatments. The MDM2/p53 ratio increased approximately 3-fold in the treated VS tumor samples as compared to the control. The differential p53 protein phosphorylation status perhaps could play an important role in VS tumor cell death due to these treatments that we reported previously.

Rohan Mitra

Rohini Keshava

Mathivanan Jothi

Vikas Vazhayil

Indira Devi Bhagavatula

Rajalakshmi Gope

BAY 61-3606, CDKi, and Sodium Butyrate Treatments Modulate p53 Protein Level and Its Site-Specific Phosphorylation in Human Vestibular Schwannomas <i>In Vitro</i>

Epithelial to mesenchymal transition is an essential step in advanced cancer development. Many master transcription factors shift their expression to drive this process, while noncoding RNAs families like miR-200 are found to restrict it. In this study we investigated how the tumor suppressor miR-204 and several transcription factors modulate main markers of mesenchymal transformation like E- and N-cadherin, SLUG, VEGF, and SOX-9 in prostate cancer cell line model (LNCaP, PC3, VCaP, and NCI-H660). We found that SLUG, E-cadherin, and N-cadherin are differentially modulated by miR-204, using miR-204 specific mimics and inhibitors and siRNA gene silencing (RUNX2, ETS-1, and cMYB). The genome perturbation associated TMPRSS2-ERG fusion coincided with shift from tumor-suppressor to tumor-promoting activity of this miRNA. The ability of miR-204 to suppress cancer cell viability and migration was lost in the fusion harboring cell lines. We found differential E-cadherin splicing corroborating to miR-204 modulatory effects. RUNX2, ETS1, and cMYB are involved in the regulation of E-cadherin, N-cadherin, and VEGFA expression. RUNX2 knockdown results in SOX9 downregulation, while ETS1 and cMYB silencing result in SOX9 upregulation in VCaP cells. Their expression was found to be also methylation dependent. Our study provides means for understanding cancer heterogeneity in regard to adapted therapeutic approaches development.

Krassimira Todorova

Diana Zasheva

Kristiyan Kanev

Soren Hayrabedyan

miR-204 Shifts the Epithelial to Mesenchymal Transition in Concert with the Transcription Factors RUNX2, ETS1, and cMYB in Prostate Cancer Cell Line Model

Double blind analysis of a batch of thirty skin tissue samples from potential prostate cancer sufferers correctly identified all &#x201c;control&#x201d; patients, patients with high and low grade prostate cancers, the presence of benign prostate hyperplasia (BPH), perineural invasions, and the one lymphatic invasion. Identification was by analysis of fibre diffraction patterns interpreted using a schema developed from observations in nine previous studies. The method, schema, and specific experiment results are reported in this paper, with some implications then drawn.

Veronica J. James

Judith M. O&#x2019;Malley Ford

Fibre Diffraction Analysis of Skin Offers a Very Early and Extremely Accurate Diagnostic Test for Prostate Cancer

<i>Aim</i>. To demonstrate the possibility of the uniqueness of colorectal cancer (CRC) in the native Nigerian by looking at the different facets of the challenges that management of this disease presents in a tertiary-care hospital in Ibadan, Nigeria. <i>Method</i>. A cohort study starting in 2009 where patients were seen in the out-patient&#x2019;s clinic. All patients who presented with features suggestive of colon or rectal cancer were studied. Biopsies were performed to confirm CRC (especially rectal cancer); patients were then booked for admission and subsequent operation. Patients were excluded if the histopathology of a resected or biopsied mass turned out to be noncancerous or inflammatory. Demographic data like age and sex were recorded. The type of operation done, findings at surgery, and the histopathology of the resected specimen were all recorded. The time taken for the pathology department to process the biopsy and resected specimens was also recorded. <i>Results</i>. 120 patients with CRC were seen over the study period of 5 years (2009&#x2013;2013) giving an average of 24 patients per annum. The male&#x2009;:&#x2009;female ratio was 1&#x2009;:&#x2009;1.14. 86 (71.7&#x25;) patients had rectal cancer while the remaining 34 (28.3&#x25;) had colon cancer. Most of the colon cancer cases were in the 51&#x2013;60 age group. The rectum&#x2009;:&#x2009;colon ratio was 2.5&#x2009;:&#x2009;1.31&#x25; of the patients were 40 years and below. 37&#x25; of those with rectal cancer were 40 years and below. 50&#x25; of resected specimens were Duke&#x2019;s B and above. 45&#x25; of patients had tumors with unfavorable grade or biology (mucinous 21.7&#x25;, signet ring 8.3&#x25;, and poorly differentiated 15&#x25;). Only 24&#x25; of patients below 40 years and 41&#x25; of those above 40 years with confirmed rectal carcinoma presented for operation. <i>Conclusion</i>. Advanced tumors at presentation may not always be as a result of late presentation. Unusual aggressiveness of the tumors may lead to rapid progression of the disease. Increasing incidence in younger patients makes abdominoperineal excision of the rectum difficult for such patients to accept.

David O. Irabor

O. Oludolapo Afuwape

Omobolaji O. Ayandipo

The Present Status of the Management of Colon and Rectal Cancer in Nigeria

Tumor cells adapt to their high metabolic state by increasing energy production. To this end, current efforts in molecular cancer therapeutics have been focused on signaling pathways that modulate cellular metabolism. However, targeting such signaling pathways is challenging due to heterogeneity of tumors and recurrent oncogenic mutations. A critical need remains to develop antitumor drugs that target tumor specific pathways. Here, we discuss an energy metabolic pathway that is preferentially activated in several cancers as a potential target for molecular cancer therapy. <i>In vitro </i>studies have revealed that many cancer cells synthesize guanosine triphosphate (GTP), via the <i>de novo</i> purine nucleotide synthesis pathway by upregulating the rate limiting enzyme of this pathway, inosine monophosphate dehydrogenase (IMPDH). Non-proliferating cells use an alternative purine nucleotide synthesis pathway, the salvage pathway, to synthesize GTP. These observations pose IMPDH as a potential target to suppress tumor cell growth. The IMPDH inhibitor, mycophenolate mofetil (MMF), is an FDA-approved immunosuppressive drug. Accumulating evidence shows that, in addition to its immunosuppressive effects, MMF also has antitumor effects via IMPDH inhibition <i>in vitro</i> and <i>in vivo</i>. Here, we review the literature on IMPDH as related to tumorigenesis and the use of MMF as a potential antitumor drug.

Nazanin Majd

Kazutaka Sumita

Hirofumi Yoshino

Dillon Chen

Jumpei Terakawa

Takiko Daikoku

Satoshi Kofuji

Richard Curry

Trisha M. Wise-Draper

Ronald E. Warnick

Jessica Guarnaschelli

Atsuo T. Sasaki

A Review of the Potential Utility of Mycophenolate Mofetil as a Cancer Therapeutic

Docetaxel-based chemotherapy regimens have substantially improved survival and recurrence rates for cancer patients. Safety profile of docetaxel regimens includes toxicities, particularly a high risk of neutropenia and febrile neutropenia. Granotax was a prospective, open label, multicentre, national phase IV study that evaluated the incidence and severity of neutropenia in adult patients with solid tumors being treated with a docetaxel-based regimen while receiving the GCSF lenograstim. Among the 394 enrolled patients the incidence of grade 3-4 neutropenia was 16.2&#x25; and of febrile neutropenia was 1.5&#x25;, far lower than the reported 85&#x2013;100&#x25; and 30&#x2013;40&#x25; incidence without G-CSFs. A total of 68 patients (17.3&#x25;) were reported to have experienced at least one grade 3-4 adverse event during the study. Two (0.5&#x25;) patients and 32 (8.1&#x25;) patients had dose delayed due to febrile neutropenia and neutropenia, respectively. Four (1.0&#x25;) patients and 32 (8.1&#x25;) patients had a dose changed due to febrile neutropenia and neutropenia, respectively. The low incidence of adverse effects and chemotherapy dose changes, delays, and withdrawals supports the use of lenograstim as effective primary prophylaxis in South African patients being treated with a docetaxel-based regimen. Furthermore, lenograstim may increase the patient&#x2019;s exposure to chemotherapy allowing patients to receive optimal dosing and duration of treatment, benefitting survival.

Samuel J. Fourie

Alicia McMaster

Rashem Mothilal

Keith I. Maart

A Phase IV Clinical Trial of Patients with Solid Tumors Receiving Lenograstim as Primary Prophylaxis for Chemotherapy-Induced Neutropenia, in a Docetaxel-Based Regimen

<i  >Background</i>. Since the preconisation presence of high-risk human papillomavirus (HR-HPV) is the main determinant of the risk of progression of preinvasive lesions; the state of the excision margins could be of less importance. Relatively little is known about the effect of human immunodeficiency virus (HIV) infection on the relation between the states of the excision margins. <i  >Methods</i>. We compared 120 HIV-infected and 139 HIV-uninfected women who underwent a hysterectomy after large loop excision of the transformation zone (LLETZ) for abnormal Pap smear. <i  >Results</i>. The excision margins had been reported negative in 21.7&#x25; of infected and 7.8&#x25; of uninfected cases (<svg     style="vertical-align:-0.1638pt;width:58.712502px;" id="M1" height="11.375" version="1.1" viewBox="0 0 58.712502 11.375" width="58.712502"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><path id="x1D443" d="M619 482q0 -69 -40.5 -119t-96 -72.5t-118.5 -26.5h-44l-70 20l-31 -151q-14 -67 0.5 -83t89.5 -22l-5 -28h-287l8 28q65 7 81.5 22t29.5 83l79 398q12 56 0.5 70.5t-78.5 20.5l7 28h255q108 0 164 -43t56 -125zM524 478q0 141 -146 141q-25 0 -47 -8q-16 -6 -20.5 -13.5&#xA;t-10.5 -39.5l-43 -241q37 -13 83 -13q67 0 125.5 45t58.5 129z" /></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><path id="x3D" d="M535 323h-483v50h483v-50zM535 138h-483v50h483v-50z" /></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><path id="x30" d="M241 635q53 0 94 -28.5t63.5 -76t33.5 -102.5t11 -116q0 -58 -11 -112.5t-34 -103.5t-63.5 -78.5t-94.5 -29.5t-95 28t-64.5 75t-34.5 102.5t-11 118.5q0 58 11.5 112.5t34.5 103t64.5 78t95.5 29.5zM238 602q-32 0 -55.5 -25t-35.5 -68t-17.5 -91t-5.5 -105&#xA;q0 -76 10 -138.5t37 -107.5t69 -45q32 0 55.5 25t35.5 68.5t17.5 91.5t5.5 105t-5.5 105.5t-18 92t-36 68t-56.5 24.5z" /></g><g transform="matrix(.017,-0,0,-.017,38.446,11.112)"><path id="x2E" d="M113 -12q-24 0 -39.5 16t-15.5 42q0 24 16 40.5t40 16.5t40 -16.5t16 -40.5q0 -26 -16 -42t-41 -16z" /></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,50.481,11.112)"><path id="x33" d="M285 378v-2q65 -13 102 -54.5t37 -97.5q0 -57 -30.5 -104.5t-74 -75t-85.5 -42t-72 -14.5q-31 0 -59.5 11t-40.5 23q-19 18 -16 36q1 16 23 33q13 10 24 0q58 -51 124 -51q55 0 88 40t33 112q0 64 -39 96.5t-88 32.5q-29 0 -64 -11l-6 29q77 25 118 57.5t41 84.5&#xA;q0 45 -26.5 69.5t-68.5 24.5q-67 0 -120 -79l-20 20l43 63q51 56 127 56h1q66 0 107 -37t41 -95q0 -42 -31 -71q-22 -23 -68 -54z" /></g>

		
	
</svg>). Three (11.5&#x25;) of 26 negative margins in HIV-infected and 2 (18.2) out of HIV-uninfected cases were falsely negative as evidenced on hysterectomy specimens (<svg     style="vertical-align:-0.1638pt;width:58.712502px;" id="M2" height="11.375" version="1.1" viewBox="0 0 58.712502 11.375" width="58.712502"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x1D443"/></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><use xlink:href="#x3D"/></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,38.446,11.112)"><use xlink:href="#x2E"/></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><path id="x37" d="M447 623l8 -12l-283 -613l-74 -10l-7 11q174 283 297 551h-216q-48 0 -62.5 -12t-33.5 -63h-29q10 60 18 148h382z" /></g><g transform="matrix(.017,-0,0,-.017,50.481,11.112)"><use xlink:href="#x33"/></g>

		
	
</svg>). The persistence rate of the initial lesion was similar in both groups (<svg     style="vertical-align:-0.1638pt;width:58.712502px;" id="M3" height="11.375" version="1.1" viewBox="0 0 58.712502 11.375" width="58.712502"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x1D443"/></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><use xlink:href="#x3D"/></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,38.446,11.112)"><use xlink:href="#x2E"/></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><path id="x32" d="M412 140l28 -9q0 -2 -35 -131h-373v23q112 112 161 170q59 70 92 127t33 115q0 63 -31 98t-86 35q-75 0 -137 -93l-22 20l57 81q55 59 135 59q69 0 118.5 -46.5t49.5 -122.5q0 -62 -29.5 -114t-102.5 -130l-141 -149h186q42 0 58.5 10.5t38.5 56.5z" /></g><g transform="matrix(.017,-0,0,-.017,50.481,11.112)"><use xlink:href="#x30"/></g>

		
	
</svg>). The persistence rate with highly active antiretroviral treatment (HAART) was similar to untreated patients (<svg     style="vertical-align:-0.1638pt;width:58.712502px;" id="M4" height="11.375" version="1.1" viewBox="0 0 58.712502 11.375" width="58.712502"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x1D443"/></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><use xlink:href="#x3D"/></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,38.446,11.112)"><use xlink:href="#x2E"/></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><use xlink:href="#x32"/></g><g transform="matrix(.017,-0,0,-.017,50.481,11.112)"><use xlink:href="#x30"/></g>

		
	
</svg>). The progression rate from low-grade to high-grade preinvasive lesions was higher in HIV-infected than HIV-uninfected women (<svg     style="vertical-align:-0.1638pt;width:66.875px;" id="M5" height="11.375" version="1.1" viewBox="0 0 66.875 11.375" width="66.875"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x1D443"/></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><use xlink:href="#x3D"/></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,38.446,11.112)"><use xlink:href="#x2E"/></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,50.481,11.112)"><use xlink:href="#x32"/></g><g transform="matrix(.017,-0,0,-.017,58.64,11.112)"><use xlink:href="#x37"/></g>

		
	
</svg>). <i  >Conclusion</i>. HIV-infected women with incomplete excision margins after LLETZ are at higher risk of progression of residual preneoplastic lesions.

Louis-Jacques van Bogaert

Implications of Post-LLETZ &#x201c;Treatment Failure&#x201d; for Further Management of HIV-Infected Women

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Journal of Cancer Research