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Low survival rates of metastatic cancers emphasize the need for a drug that can

prevent and/or treat metastatic cancer. αv integrins are involved in essential

processes for tumor growth and metastasis and targeting of αv integrins has been

shown to decrease angiogenesis, tumor growth and metastasis. In this study, the

role of αv integrin and its potential as a drug target inbladder cancer was

investigated. Treatment with an αv integrin antagonist as well as knockdown of

αv integrin in the bladdercarcinoma cell lines, resulted in reduced malignancy

invitro, as illustrated by decreased proliferative, migratory and clonogenic

capacity. The CDH1/CDH2 ratio increased, indicating a shift towards a more

epithelial phenotype. This shift appeared to be associated with downregulation of

EMT-inducing transcription factors including SNAI2. The expression levels of

1. Targeting of Alpha-V Integrins Reduces Malignancy

of Bladder Carcinoma

Department of Urology, Leiden University Medical Centre, Leiden, The

Netherlands

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the self-renewal genes NANOG

and BMI1 decreased as well as the

number of cells with high

Aldehyde Dehydrogenase

activity. In addition, self-renewal

ability decreased as measured with

the urosphere assay. In line with

these observations, knockdown or

treatment of αv integrins resulted

in decreased metastatic growth in

preclinical invivo models as assessed by bioluminescence imaging. In conclusion,

we show that αv integrins are involved in migration, EMT and maintenance of

Aldehyde Dehydrogenase activity in bladder cancer cells. Targeting of αv

integrins might be a promising approach for treatment and/or prevention of

metastatic bladder cancer.

AIM:

The aim of this study was to evaluate the potential role of C-

choline-PET/CT in nodal assessment in patients with bladder

cancer (BCa) using the pathological specimen as reference standard.

PATIENTS AND METHODS:

Fifty-nine patients with proven BCa were retrospectively enrolled from April

2011 to January 2014 (mean [SD] age, 70.1 [9] years; range 49-85 years). Of 59

patients, 39 (staging group) were referred to C-choline-PET/CT for preoperative

lymph node (LN) evaluation before radical cystectomy and extended pelvic LN

dissection. Of the 59 patients, 29 (restaging group) had C-choline-PET/CT for

suspected BCa relapse after primary radical surgery. In both groups, C-choline-

PET/CT findings were correlated with histology. Sensitivity, specificity, positive

PLoS One. 2014 Sep 23;9(9):e108464. doi: 10.1371/journal.pone.0108464. eCollection 2014.

2. 11C-Choline PET/CT and Bladder Cancer: Lymph Node

Metastasis Assessment with Pathological Specimens as

Reference Standard

Department of Urology, Policlinico S. Orsola-Malpighi, University of Bologna,

Bologna, Italy

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predictive value, negative predictive value, and accuracy were calculated to

assess C-choline-PET/CT feasibility in LN assessment. Age, TNM, histology,

and previous chemotherapy were analyzed as additional predictive factors.

RESULTS:

C-choline-PET/CT overall detection rate was 62.7% (37/59 patients). On a

regional-based analysis, C-choline-PET/CT was considered positive for

primary cancer and/or local relapse in bladder bed in 54.2% of the patients

(32/59). Pathological LN uptake was reported in 23.7% of the patients (14/59)

and systemic choline deposit (bone or lung) in 11.8% of the patients (7/59).

Considering LN metastasis detection, compared with histological analysis, C-

choline-PET/CT showed in the whole population a sensitivity, specificity,

positive predictive value, negative predictive value, and accuracy of 59%, 90%,

71%, 84%, and 81%, respectively. No other investigated factors reached

statistical significance.

CONCLUSIONS:

C-choline-PET/CT may provide additional diagnostic information in

preoperative nodal staging of patients with BCa and be considered a useful tool

to restage patients with BCa suspected of relapse. Further studies are needed to

assess if C-choline-PET/CT could have an influence on survival of patients with

BCa.

Clin Nucl Med. 2014 Sep 22

Urinary bladder cancer, PET/CT

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BACKGROUND:

Electrochemotherapy is widely used for treatment of solid tumors; however

experience in bladder cancer is limited.

PURPOSE:

To investigate mitomycin C (MMC) and cisplatin (CIS) for their use with

electrochemotherapy in bladder cancer in-vitro and in-vivo.

MATERIALS AND METHODS:

The human bladder cancer cell line SW780 was used. Cells were treated with

electroporation (EP), drug alone or EP+drug respectively, in increasing

concentrations of either MMC or CIS ranging from respectively 0.001μM to

2000μM and 1.56μM to 300μM. EP parameters: eight pulses of 1.2kV/cm, 99μs,

1Hz. Survival and apoptosis (caspase activity) were investigated. Nude mice

(NMRI-Fox1nu) were inoculated subcutaneously and randomized to: a)

EP+NaCl, b) NaCl alone, c) EP+drug, d) drug alone. Drugs were: MMC (5mM)

3. In vitro and in vivo experiments on electrochemotherapy

for bladder cancer

Center for Experimental Drug and Gene Electrotransfer, Department of

Oncology, Copenhagen University Hospital Herlev, Denmark.

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and CIS (250mM). Tumors were measured thrice weekly. A similar experiment

investigated necrosis by histology at days 2 and 6.

RESULTS:

and conclusions: In vitro, MMC cytotoxicity (p=0.9057) and caspase activity

(p=0.53) was unaffected by EP. However, EP caused a 6.6-fold increased

cytotoxicity (p<0.0001) and a higher caspase activity (p<0.001) with CIS. In-vivo

"EP+MMC" showed tumor volume reduction (p<0.0005). Survival for

"EP+MMC" and "MMC alone" were higher than controls (p=0.0004). Tumor

response: "EP+MMC" (100%), "MMC alone" (53%), "EP+NaCl" (14%), "NaCl

alone" (0%). In-vivo "EP+CIS" showed slower tumor growth (p=0.0005) over

other combinations with significantly higher survival (p=0.0003). Tumor

response: EP+CIS" (47%), "CIS alone" (0%), "EP+NaCl" (0%), "NaCl alone"

(8%). In-vivo electrochemotherapy with MMC or CIS is more effective than

chemotherapy alone in a bladder cancer tumor model, opening new perspectives

in bladder cancertherapy.

OBJECTIVE:

To summarize the diagnosis, surgical intervention and

postoperative management of patients with

urothelialcancer (UC) after renal transplants (RTx).

METHODS:

In our retrospective review of 3,370 RTx recipients in our transplant center from

1974 to 2012, all recipients underwent routine checkups and follow-up. Imaging

was performed in all patients suspected of having malignancies, and the

histological cell type of the specimen slices was reappraised by pathologists. The

data of all recipients with malignancies were retrospectively reviewed to

determine clinical characteristics after RTx.

J Urol. 2014 Sep 19. pii: S0022-5347(14)04435-8. doi: 10.1016/j.juro.2014.09.039.

4. A retrospective review of patients with urothelial cancer in

3,370 recipients after renal transplantation: a single-center

experience

Department of Urology, Beijing Friendship Hospital, Capital Medical

University, Beijing, 100050, China

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RESULTS:

A total of 169 patients of the cohort of 3,370

had malignancies after RTx. Of 180 tumors,

106 tumors were confirmed as UC. Fifty-two

patients had taken drugs containing

aristolochic acid. The median time to neoplasia

after RTx in the group taking aristolochic acid

(30 months) was significantly less than in those

not taking aristolochic acid (60.3 months). We

recommended surgical intervention for RTx

recipients with UC, transurethral resection

of bladder tumors for patients with solitary or

concomitant superficial UC, and radical

cystectomy for high-risk bladder UC. We

performed simultaneous bilateral or unilateral nephroureterectomy in patients

with upper urinary tract UC.

CONCLUSION:

Our results suggest that UC is the predominant tumor in Chinese RTx recipients

and that regular urinalysis and imaging are needed in all recipients after RTx,

especially women with a history of taking aristolochic acid. Surgical

interventions did not increase the risk beyond that in UC patients without RTx.

OBJECTIVE:

The location of positive lymph nodes (LNs) is

important for bladder cancer staging. Little is known regarding the impact of

perivesical (PV) lymph node (PVLN) involvement on survival. This study

characterized PVLN identified after radical cystectomy (RC) and analyzed their

impact on recurrence and survival.

MATERIALS AND METHODS:

World J Urol. 2014 Sep 20

5. Significance of perivesical lymph nodes in radical

cystectomy for bladder cancer

Institute of Urology, Norris Comprehensive Cancer Center, Keck School of

Medicine, University of Southern California, Los Angeles, CA

Herbal Medicine and Aristolochic Acid

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We reviewed our institutional review

board-approved database including all

patients who underwent RC with

pelvic lymphadenectomy for curative

intent for urothelial carcinoma.

Clinical and pathologic data were

obtained. Patients were analyzed in

groups according to the location of

positive LNs: PV+/other LN (ON)+,

PV+/ON-, and PV-/ON+. Kaplan-Meier curves were used to estimate recurrence-

free survival (RFS) and overall survival (OS). Multivariable Cox regression

(including pathologic T category, number of positive LNs, highest level of

positive LNs, chemotherapy, and margin status) was performed to evaluate

associations between PVLN status and survival.

RESULTS:

In total, 2,017 patients met

inclusion criteria and 465 (23%)

were LN+. PVLNs were

identified in 936 patients (47%),

positive in 197 patients (10%),

and represented isolated

LN+disease in 101 patients

(5%). On univariate analysis,

RFS and OS were significantly

worse in the PV+/ON+group

compared with the PV+/ON-

and PV-/ON+ groups. There

were no significant differences

in RFS or OS between the

PV+/ON- and PV-/ON+ groups.

On multivariable analysis, PV+/ON+disease was independently associated with

worse RFS and OS when compared with PV-/ON+ disease.

CONCLUSIONS:

PVLNs were identified in a significant number of patients after RC. Positive

PVLN, when in combination with other positive LNs, portends worse survival

even when correcting for the number of positive nodes.

Urol Oncol. 2014 Sep 16. pii: S1078-1439(14)00281-6. doi: 10.1016/j.urolonc.2014.08.004.

lymphatic landing sites (n = 284 of 60 bladder sites

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BACKGROUND

Emerging evidence shows that nanomechanical phenotypes of circulating tumor

cells (CTC) could become potential biomarkers for metastatic castration resistant

prostate cancer (mCRPC).

METHODS

To determine the nanomechanical phenotypes of CTCs we applied atomic force

microscopy (AFM) employing the PeakForce quantitative nanomechanical

(QNM) imaging. We assessed biophysical parameters (elasticity, deformation,

and adhesion) of 130 CTCs isolated from blood samples from five castration

sensitive (CS) and 12 castration resistant prostate cancer (CRPCa) patients.

RESULTS

We found that CTCs from CRPCa patients are three times softer, three times more

deformable, and seven times more adhesive than counterparts from CSPCa

patients. Both nonsupervised hierarchical clustering and principle component

analysis show that three combined nanomechanical parameters could constitute a

valuable set to distinguish between CSPCa and CRPCa.

6. Nanomechanical biomarkers of single circulating tumor

cells for detection of castration resistant prostate cancer

Department of Molecular Medicine, University of Texas Health Science Center,

San Antonio, Texas

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CONLUSIONS

Our study indicates that nanomechanical phenotypes of CTCs may serve as novel

and effective biomarkers for mCRPC.

Objectives

To evaluate the impact of glycemic control of diabetes mellitus (DM) on prostate

cancer detection in a biopsy population.

Patients and Methods

We retrospectively

reviewed the records of

1,368 men who

underwent prostate

biopsy at our institution.

We divided our biopsy

population into three

groups according to

their history of DM, and

their Hemoglobin A1c

(HbA1c) level: a no-DM

(DM−) group; a good

glycemic control

(DM+GC) group (HbA1c <6.5%); and a poor glycemic control (DM+PC) group

(HbA1c ≥6.5%). For sub-analyses, the DM+PC group was divided into a

moderately poor glycemic control (DM+mPC) group (6.5≤ HbA1c <7.5%) and a

severely poor glycemic control (DM+sPC) group (HbA1c ≥7.5%).

The Prostate, Volume 74, Issue 13, pages 1297–1307, September 2014

7. Poor Glycemic Control of Diabetes Mellitus Is Associated

with Higher Risk of Prostate Cancer Detection in a Biopsy

Population

Department of Urology, Seoul Metropolitan Government Seoul National

University Boramae Medical Center, Dongjak-gu, Seoul, Korea

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Results

Among 1,368 men, 338 (24.7%) had a history of DM, and 393 (28.7%) had a

positive biopsy. There was a significant difference in prostatic specific antigen

density (PSAD) (P = 0.037) and the frequency of abnormal DRE findings (P =

0.031) among three groups. The occurrence rate of overall prostate cancer

(P<0.001) and high-grade prostate cancer (P = 0.016) also presented with a

significantly difference. In the multivariate analysis, the DM+PC group was

significantly associated with a higher rate of overall prostate cancer detection in

biopsy subjects compared to the DM− group (OR = 2.313, P = 0.001) but the

DM+PC group was not associated with a higher rate of high-grade (Gleason score

≥7) diseases detected during the biopsy (OR = 1.297, P = 0.376). However, in

subgroup analysis, DM+sPC group was significantly related to a higher risk of

high-grade diseases compared to the DM− group (OR = 2.446, P = 0.048).

Conclusions

Poor glycemic control of DM was associated with a higher risk of prostate cancer

detection, including high-grade disease, in the biopsy population.

OBJECTIVE. The purpose of this study was to

investigate whether retroperitoneal craniocaudal nodal length or nodal volume

predicts relapse risk in stage I testicular cancer. MATERIALS AND METHODS.

We retrospectively reviewed

826 testicularcancer patients. Of these 826

patients, 118 had stage I disease and either

less than 2 years of surveillance or

retroperitoneal lymph node dissection with

no adjuvant chemotherapy. These patients

formed our analytic cohort, and 3D nodal

volumes and craniocaudal nodal length

PLOS ONE, Published: September 08, 2014, DOI: 10.1371/journal.pone.0104789

8. Craniocaudal Retroperitoneal Node Length as a Risk

Factor for Relapse From Clinical Stage ITesticular Germ

Cell Tumor

Departments of Oncology, Radiology, and Radiation Oncology, Dana

Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02115.

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were measured. Association

between relapse risk and

craniocaudal nodal length and

nodal volume was evaluated using

univariable or multivariable

logistic regression models

adjusted for known prognostic

factors. RESULTS. Sixty-six

(56%) of 118 patients had

nonseminomatous germ cell

tumor and 52 (44%) had

seminomatous germ cell tumor.

Craniocaudal nodal length proved

to be an independent risk factor in nonseminomatous germ cell tumors using a

multivariable logistic regression

model adjusting for other

potential known risk factors of

embryonal predominance and

lymphovascular invasion. For

every 3-mm increase in

craniocaudal nodal length, the

risk of relapse increased by 52%

(odds ratio [OR], 1.52; 95% CI,

1.03-2.25). For patients with

seminomas, only primary tumor

size was an independent risk factor for relapse (1.34, 1.02-1.75). CONCLUSION.

In nonseminomatous germ cell tumors, craniocaudal nodal length was shown to

be associated with increased risk of relapse independently of other known risk

factors. If validated in an independent cohort, craniocaudal nodal length could

provide important additional information to inform management decisions in

these patients.

AJR Am J Roentgenol. 2014 Oct;203(4):W415-W420.

Germ Cell Tumor

دفترچه های دارندگاندرمان رورش ، ـوزش و پـح ،آمـسلـای مـروهـنی

یدهـیاد شـنـرو ، بـیـداد ، وزارت نـه امـیتـکم

.انجام می پذیرد رایگاندر این مرکز

طرف قرارداد بیمه های تامین اجتماعی

خدمات درمانی

نیروهای مسلح

امامکمیته امداد

بیمه ایران

بیمه دانا

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