Surgical cytoreduction for recurrent epithelial ovarian cancer.

Background: The standard management of primary ovarian cancer is optimal cytoreductive surgery followed by platinum-based chemotherapy. Most women with primary ovarian cancer achieve remission on this combination therapy. For women achieving clinical remission after completion of initial treatment, most (60%) with advanced epithelial ovarian cancer will ultimately develop recurrent disease.

Primary esophageal and gastro-esophageal junction cancer xenograft models: clinicopathological features and engraftment.

There are very few xenograft models available for the study of esophageal (E) and gastro-esophageal junction (GEJ) cancer. Using a NOD/SCID model, we implanted 90 primary E and GEJ tumors resected from patients and six endoscopic biopsy specimens. Of 69 resected tumors with histologically confirmed viable adenocarcinoma or squamous cell carcinoma, 22 (32%) was engrafted.

Analysis of para-aortic lymphadenectomy up to the level of the renal vessels in apparent early-stage ovarian cancer.

Objective: The aim of this study was to evaluate the impact of para-aortic lymphadenectomy up to the renal vessels on the accurate staging in ovarian cancer patients presumed preoperatively to be confined to the ovary.

Methods: We retrospectively analyzed data on 124 patients with primary epithelial ovarian cancer who were preoperatively thought to have tumor confined to the ovary and underwent primary staging surgery. The distribution of lymph node metastasis and various risk factors for nodal involvement were investigated.

Imatinib radiosensitizes bladder cancer by targeting homologous recombination.

Radiotherapy is a major treatment modality used to treat muscle-invasive bladder cancer, with patient outcomes similar to surgery. However, radioresistance is a significant factor in treatment failure. Cell-free extracts of muscle-invasive bladder tumors are defective in nonhomologous end-joining (NHEJ), and this phenotype may be used clinically by combining radiotherapy with a radiosensitizing drug that targets homologous recombination, thereby sparing normal tissues with intact NHEJ.

Impact of race and ethnicity on treatment and survival of women with vulvar cancer in the United States.

Objective: To examine racial/ethnic differences in treatment and survival in women diagnosed with invasive vulvar cancer in the United States.

Methods: Women with invasive vulvar cancer were identified from the Surveillance, Epidemiology, and End Results database from 1/1/92 to 12/31/02. Statistical analysis using Chi-square, Fisher's Exact Test, Kaplan-Meier survival methods, and Cox regression proportional hazards models was performed.

Ovarian malignancy risk stratification of the adnexal mass using a multivariate index assay.

Objective: To validate the effectiveness of a multivariate index assay in identifying ovarian malignancy compared to clinical assessment and CA125-II, among women undergoing surgery for an adnexal mass after enrollment by non-gynecologic oncology providers.

Methods: A prospective, multi-institutional trial enrolled female patients scheduled to undergo surgery for an adnexal mass from 27 non-gynecologic oncology practices. Pre-operative serum samples and physician assessment of ovarian cancer risk were correlated with final surgical pathology.

Changes in apparent diffusion coefficient and T2 relaxation during radiotherapy for prostate cancer.

Purpose: To evaluate regional and temporal changes in apparent diffusion coefficient (ADC) and T2 relaxation during radiation therapy (RT) in patients with low and intermediate risk localized prostate cancer.

Materials And Methods: Seventeen patients enrolled on a prospective clinical trial where MRI was acquired every 2 weeks throughout eight weeks of image-guided prostate IMRT (78 Gy/39 fractions). ADC and T2 quantification used entire prostate, central gland, benign peripheral zone, and tumor-dense regions-of-interest, and mean values were evaluated for common response trends.

Protease nexin 1 inhibits hedgehog signaling in prostate adenocarcinoma.

Prostate adenocarcinoma (CaP) patients are classified into low-, intermediate-, and high-risk groups that reflect relative survival categories. While there are accepted treatment regimens for low- and high-risk patients, intermediate-risk patients pose a clinical dilemma, as treatment outcomes are highly variable for these individuals. A better understanding of the factors that regulate the progression of CaP is required to delineate risk.

AZD5438, an inhibitor of Cdk1, 2, and 9, enhances the radiosensitivity of non-small cell lung carcinoma cells.

Purpose: Radiation therapy (RT) is one of the primary modalities for treatment of non-small cell lung cancer (NSCLC). However, due to the intrinsic radiation resistance of these tumors, many patients experience RT failure, which leads to considerable tumor progression including regional lymph node and distant metastasis. This preclinical study evaluated the efficacy of a new-generation cyclin-dependent kinase (Cdk) inhibitor, AZD5438, as a radiosensitizer in several NSCLC models that are specifically resistant to conventional fractionated RT.

Association between germline HOXB13 G84E mutation and risk of prostate cancer.

Recently, a G84E mutation in HOXB13, a gene involved in prostate development, was shown to be strongly associated with an increased risk of prostate cancer. To confirm this association in a screening setting, we conducted a case-control study and sequenced germline DNA from peripheral leukocytes of 1843 men diagnosed with prostate cancer (case subjects) and 2225 men without prostate cancer (control subjects) for mutations in HOXB13. Subjects (aged 40-94 years) were prescreened and underwent a prostate biopsy at two tertiary care centers in Canada.

Impact of complete cytoreduction leaving no gross residual disease associated with radical cytoreductive surgical procedures on survival in advanced ovarian cancer.

Background: To analyze the impact of radical cytoreductive surgery-as part of primary tumor debulking-on the amount of residual tumor and survival in patients with advanced ovarian cancer and to evaluate the prognostic significance of no gross residual disease (RD) after surgery.

Methods: Medical records of 203 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC-IV ovarian cancer were reviewed. All patients underwent primary cytoreductive surgery followed by taxane- and platinum-based chemotherapy.

Neoplastic cell response to tiopronin-coated gold nanoparticles.

Unlabelled: The present study characterized the in vitro biological response of a comprehensive set of cancer cell lines to gold nanoparticles (2.7 nm) coated with tiopronin (AuNPs-TP). Our findings suggest that upon entering cells, the AuNPs-TP are sequestered in vacuoles such as endosomes and lysosomes, and mostly localize in perinuclear areas.

Electron transfer-based combination therapy of cisplatin with tetramethyl-p-phenylenediamine for ovarian, cervical, and lung cancers.

The platinum-based chemotherapy is the standard treatment for several types of cancer. However, cancer cells often become refractory with time and most patients with serious cancers die of drug resistance. Recently, we have discovered a unique dissociative electron-transfer mechanism of action of cisplatin, the first and most widely used platinum-based anticancer drug.

Prognostic significance of systematic lymphadenectomy as part of primary debulking surgery in patients with advanced ovarian cancer.

Objective: The objective of this study was to evaluate the impact of systematic pelvic and para-aortic lymphadenectomy on survival in patients with advanced ovarian cancer.

Methods: We retrospectively analyzed the data of 189 consecutive patients with FIGO stage IIIC ovarian cancer between 2000 and 2011, who underwent primary cytoreductive surgery followed by platinum- and taxane-based chemotherapy. All patients were classified into two groups - patients who underwent systematic pelvic and para-aortic lymphadenectomy and those who did not.

Rectosigmoid resection at the time of primary cytoreduction for advanced ovarian cancer. A multi-center analysis of surgical and oncological outcomes.

Objective: The aim of the study was to determine the impact of rectosigmoid resection, at the time of primary cytoreductive surgery, on morbidity and survival of patients with advanced ovarian cancer.

Methods: We performed a retrospective medical chart review of patients who underwent rectosigmoid resection for ovarian, tubal and peritoneal cancers between 1998 and 2008 at the IEO in Milan and JHMI in Baltimore. Perioperative and follow-up data were collected.

From sequence to molecular pathology, and a mechanism driving the neuroendocrine phenotype in prostate cancer.

The current paradigm of cancer care relies on predictive nomograms which integrate detailed histopathology with clinical data. However, when predictions fail, the consequences for patients are often catastrophic, especially in prostate cancer where nomograms influence the decision to therapeutically intervene. We hypothesized that the high dimensional data afforded by massively parallel sequencing (MPS) is not only capable of providing biological insights, but may aid molecular pathology of prostate tumours.

A model for prediction of parametrial involvement and feasibility of less radical resection of parametrium in patients with FIGO stage IB1 cervical cancer.

Objective: The objective of this study was to evaluate the potential risk factors associated with parametrial invasion and to identify preoperatively a subgroup of patients at low risk for parametrial involvement who could be appropriate candidates for less radical surgery in FIGO stage IB1 cervical cancer.

Methods: We retrospectively reviewed the medical records of 317 FIGO stage IB1 cervical cancer patients undergoing class III radical hysterectomy and bilateral pelvic lymphadenectomy. Clinocopathologic factors associated with parametrial invasion were analyzed and the risk criteria predicting parametrial involvement were calculated using a logistic regression model.

Tumor hypoxia predicts biochemical failure following radiotherapy for clinically localized prostate cancer.

Purpose: Tumor hypoxia is an important determinant of outcome in many human malignancies and is associated with treatment resistance and metastases. The aim of this study was to determine the effect of hypoxia in patients with prostate cancer treated with radiotherapy.

Experimental Design: Tumor hypoxia was measured in 247 patients with clinically localized prostate cancer before radiotherapy, with or without hormonal therapy.

Discordance between phosphorylation and recruitment of 53BP1 in response to DNA double-strand breaks.

During the DNA damage response (DDR), chromatin modifications contribute to localization of 53BP1 to sites of DNA double-strand breaks (DSBs). 53BP1 is phosphorylated during the DDR, but it is unclear whether phosphorylation is directly coupled to chromatin binding. In this study, we used human diploid fibroblasts and HCT116 tumor cells to study 53BP1 phosphorylation at Serine-25 and Serine-1778 during endogenous and exogenous DSBs (DNA replication and whole-cell or sub-nuclear microbeam irradiation, respectively).

Evolution of surgical treatment paradigms for advanced-stage ovarian cancer: redefining 'optimal' residual disease.

Over the past 40 years, the survival of patients with advanced ovarian cancer has greatly improved due to the introduction of combination chemotherapy with platinum and paclitaxel as standard front-line treatment and the progressive incorporation of increasing degrees of maximal cytoreductive surgery. The designation of "optimal" surgical cytoreduction has evolved from residual disease ≤ 1 cm to no gross residual disease. There is a growing body of evidence that patients with no gross residual disease have better survival than those with optimal but visible residual disease.

Surgical management of epithelial ovarian cancer.

Ovarian cancer affects approximately 21,880 women and accounts for over 13,000 deaths annually in the United States. Although survival rates have improved over the past several decades, directly as a result of advances in chemotherapy and surgery, ovarian cancer continues to have high mortality rates. Understanding the multiple roles of surgery throughout the disease course is the focus of this review.

Integrated genome and transcriptome sequencing identifies a novel form of hybrid and aggressive prostate cancer.

Next-generation sequencing is making sequence-based molecular pathology and personalized oncology viable. We selected an individual initially diagnosed with conventional but aggressive prostate adenocarcinoma and sequenced the genome and transcriptome from primary and metastatic tissues collected prior to hormone therapy. The histology-pathology and copy number profiles were remarkably homogeneous, yet it was possible to propose the quadrant of the prostate tumour that likely seeded the metastatic diaspora.

Pathological predictors for site of local recurrence after radiotherapy for prostate cancer.

Purpose: Rational design of targeted radiotherapy (RT) in prostate cancer (Pca) hinges on a better understanding of spatial patterns of recurrence. We sought to identify pathological factors predictive for site of local recurrence (LR) after external beam RT.

Methods And Materials: Prospective databases were reviewed to identify men with LR after RT from 1997 through 2009.