Priya Patel

Overexpression of KIF23 predicts clinical outcome in primary lung cancer patients.

OBJECTIVE High-level expression of kinesin family member 23 (KIF23), a member of microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division, has been observed in a variety of human malignancies. The aims of the present study were to observe the expression of KIF23 in lung cancer, examine the role of KIF23 in lung cancer cell growth and/or survival by small interfering RNA experiments, and explore its clinicopathologic significance and evaluate KIF23 expression as a prognostic marker. MATERIALS AND METHODS Quantitative reverse transcription-polymerase chain reaction analysis was performed to detect the expression of KIF23 mRNA using metastatic lymph nodes from patients with advanced lung cancer obtained by endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA) and primary lung tumors through surgical sample. The role of KIF23 in cancer cell growth was examined by small interfering RNA experiments. A total of 339 lung cancers were analyzed immunohistochemically on tissue microarrays to examine the expression of KIF23 protein and its clinicopathologic significance. RESULTS KIF23 transcript was found to be overexpressed in the great majority of metastatic lymph nodes from advanced lung cancers and primary lung tumors. Inhibiting KIF23 expression effectively suppressed lung cancer cell growth. High-level KIF23 expression was observed in 67.8% of the 339 cases. Lung adenocarcinoma patients with tumors displaying a high-level of KIF23 expression was also identified as an independent prognostic factor by multivariate analysis (P=0.0064). CONCLUSION KIF23 not only provides additional prognostic information for surgical treatment of lung cancer, but may also be a novel therapeutic target for these patients.

Flexible 19-Gauge Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Needle: First Experience

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a well-established first-line invasive modality for mediastinal lymph node staging in lung cancer patients and in the diagnostic workup of patients with mediastinal adenopathy. With the current 21- and 22-gauge (G) EBUS-TBNA needles, the procedure can be limited by the degree of flexibility in the needle and the size of the lumen in tissue acquisition. Objective: We report our initial experience with a first-generation flexible 19-G EBUS-TBNA (Flex 19G; Olympus Respiratory America, Redmond, WA, USA) needle with regards to efficacy and safety. Methods: The Flex 19G EBUS-TBNA needle was used in 47 selected patients with enlarged hilar and/or mediastinal lymphadenopathy at 3 centers. The standard Olympus EBUS scope with a 2.2-mm working channel was used in all cases. Results: The diagnostic yield of the Flex 19G needle according to clinical cytopathology reports was 89% (42/47). The diagnosis and their respective diagnostic yield with the Flex 19G EBUS-TBNA needle were malignancy 24/27 (89%), sarcoidosis 13/14 (93%), and reactive lymph node hyperplasia 5/6 (83%). The mean short axis of the sampled lymph nodes was 19 ± 9 mm. No complications occurred except for 1 instance of moderate bleeding, which did not require intervention beyond suctioning and subsequently resolved. All 13 patients diagnosed with adenocarcinoma by the 19-G needle had sufficient tissue for genetic testing. Conclusion: EBUS-TBNA using the first-generation Flex 19G needle is feasible and safe with promising diagnostic yield while providing a greater degree of flexion with the Olympus EBUS scope. Additional clinical evaluations are warranted.

A novel minimally invasive near-infrared thoracoscopic localization technique of small pulmonary nodules: A phase I feasibility trial

Objectives Localization and resection of nonvisible, nonpalpable pulmonary nodules during video‐assisted thoracoscopic surgery are challenging. Our study was to determine the feasibility and safety of indocyanine green fluorescence localization and resection of small nodules using a near‐infrared fluorescence thoracoscope. Methods Twenty patients with undiagnosed peripheral nodules smaller than 3 cm scheduled for computed tomography–guided microcoil placement followed by video‐assisted thoracoscopic surgery wedge resection were enrolled. After microcoil deployment, 100 to 150 &mgr;L of diluted indocyanine green was injected percutaneously near the nodule. The nodule initially was localized solely by using a near‐infrared thoracoscope to visualize indocyanine green fluorescence. Thoracoscopic instruments were used to determine the staple line. Wedge resection was performed after confirmation of the location of the microcoil using fluoroscopy. Results Twenty patients underwent near‐infrared, image‐guided, video‐assisted thoracoscopic surgery resection. The median computed tomography tumor size was 1.2 cm. The median depth from the pleural surface was 1.4 cm (range, 0.2‐4.8 cm). The median computed tomography–guided intervention time was 35 minutes, and video‐assisted thoracoscopic surgery procedural time was 54 minutes. Indocyanine green fluorescence was clearly identified in 18 of 20 patients (90%). The surgical margins were all negative on final pathology without the need for additional resection. The final diagnoses included 18 primary lung cancers, 1 metastatic lung cancer, and 1 benign lung tumor. Conclusions Computed tomography–guided percutaneous indocyanine green injection and intraoperative near‐infrared localization of small nodules are safe and feasible. These offer surgeons the ease of localization through direct indocyanine green fluorescence imaging without the use of fluoroscopy and may be a complementary technique to preoperative microcoil placement for nonvisible, nonpalpable intrapulmonary nodules.

Multi-Modal Imaging in a Mouse Model of Orthotopic Lung Cancer

Background Investigation of CF800, a novel PEGylated nano-liposomal imaging agent containing indocyanine green (ICG) and iohexol, for real-time near infrared (NIR) fluorescence and computed tomography (CT) image-guided surgery in an orthotopic lung cancer model in nude mice. Methods CF800 was intravenously administered into 13 mice bearing the H460 orthotopic human lung cancer. At 48 h post-injection (peak imaging agent accumulation time point), ex vivo NIR and CT imaging was performed. A clinical NIR imaging system (SPY®, Novadaq) was used to measure fluorescence intensity of tumor and lung. Tumor-to-background-ratios (TBR) were calculated in inflated and deflated states. The mean Hounsfield unit (HU) of lung tumor was quantified using the CT data set and a semi-automated threshold-based method. Histological evaluation using H&E, the macrophage marker F4/80 and the endothelial cell marker CD31, was performed, and compared to the liposomal fluorescence signal obtained from adjacent tissue sections Results The fluorescence TBR measured when the lung is in the inflated state (2.0 ± 0.58) was significantly greater than in the deflated state (1.42 ± 0.380 (n = 7, p<0.003). Mean fluorescent signal in tumor was highly variable across samples, (49.0 ± 18.8 AU). CT image analysis revealed greater contrast enhancement in lung tumors (a mean increase of 110 ± 57 HU) when CF800 is administered compared to the no contrast enhanced tumors (p = 0.0002). Conclusion Preliminary data suggests that the high fluorescence TBR and CT tumor contrast enhancement provided by CF800 may have clinical utility in localization of lung cancer during CT and NIR image-guided surgery.

Addressing comorbidities in psoriatic disease

Psoriasis and PsA are associated with comorbidities including cardiovascular disease, obesity, metabolic syndrome and depression. The purpose of this study was to examine if patients recognize that they are being monitored for comorbidities associated with their condition, and to determine which physicians are managing these comorbidities. Patients with psoriasis without arthritis (PsC) and patients with PsA were recruited from the University of Toronto Psoriasis Cohort and Psoriatic Arthritis Clinic, respectively. A comorbidity questionnaire was developed through a literature review and patients completed the questionnaire at clinic visits or over the telephone. PsA patient responses were compared with information recorded by physicians at clinic visits. A total of 268 patients (103 PsC and 164 PsA) were included. Patients indicated having their blood pressure (96.3%), weight (94.4%), blood sugar (75%) and cholesterol (79.5%) levels checked, with PsA patients indicating being checked more frequently than PsC patients. PsA patients were most uncertain about whether their blood sugar and cholesterol levels were checked by physicians. The highest correlation between patient responses and physician records occurred for medications for diabetes, depression and hypercholesterolemia. Patients indicated their family physician were most responsible in monitoring the comorbidities. Overall, patients documented being moderately well screened for most comorbidities and were most unsure about having their blood sugar and cholesterol levels monitored. Patient education and records should be improved at clinic visits, as there are discrepancies between patient responses and physician records regarding the presence and treatment of comorbidities.

Personalized siRNA-Nanoparticle Systemic Therapy using Metastatic Lymph Node Specimens Obtained with EBUS-TBNA in Lung Cancer

Inhibiting specific gene expression with siRNA provides a new therapeutic strategy to tackle many diseases at the molecular level. Recent strategies called high-density lipoprotein (HDL)-mimicking peptide-phospholipid nanoscaffold (HPPS) nanoparticles have been used to induce siRNAs-targeted delivery to scavenger receptor class B type I receptor (SCARB1)-expressing cancer cells with high efficiency. Here, eight ideal therapeutic target genes were identified for advanced lung cancer throughout the screenings using endobronchial ultrasonography–guided transbronchial needle aspiration (EBUS-TBNA) and the establishment of a personalized siRNA-nanoparticle therapy. The relevance of these genes was evaluated by means of siRNA experiments in cancer cell growth. To establish a therapeutic model, kinesin family member-11 (KIF11) was selected as a target gene. A total of 356 lung cancers were analyzed immunohistochemically for its clinicopathologic significance. The antitumor effect of HPPS-conjugated siRNA was evaluated in vivo using xenograft tumor models. Inhibition of gene expression for these targets effectively suppressed lung cancer cell growth. SCARB1 was highly expressed in a subset of tumors from the lung large-cell carcinoma (LCC) and small-cell lung cancer (SCLC) patients. High-level KIF11 expression was identified as an independent prognostic factor in LCC and squamous cell carcinoma (SqCC) patients. Finally, a conjugate of siRNA against KIF11 and HPPS nanoparticles induced downregulation of KIF11 expression and mediated dramatic inhibition of tumor growth in vivo. Implications: This approach showed delivering personalized cancer-specific siRNAs via the appropriate nanocarrier may be a novel therapeutic option for patients with advanced lung cancer. Mol Cancer Res; 16(1); 47–57. ©2017 AACR.