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1.  A multidisciplinary approach to giant soft tissue sarcoma of the chest wall: A case report 
•Chest wall sarcomas most commonly present as painless slow growing masses.•Resection is often precarious due to involvement of important structures.•The multidisciplinary approach is crucial for the optimal management of this tumor.
Soft tissue sarcomas of the chest wall are exceptionally rare entities that present as painless slow growing masses. Resection is often precarious due to involvement of vital structures, and patients are left with large chest wall defects postoperatively requiring extensive reconstruction.
Presentation of case
We present a case report of a 29 year-old man who presented with a giant soft tissue sarcoma of the chest that had been growing slowly for one year prior to presentation. The patient had a biopsy that was positive for sarcoma, and PET CT demonstrated a large lobulated mass in the left chest wall with an SUV of 6.7. He received 50 Gy of radiation therapy; however, the mass continued to grow in size. He subsequently underwent an en-bloc resection of the mass with latissimus and serratus muscle primary reconstruction. Final pathology showed a 27 cm high-grade fibrosarcoma with prominent myxoid component. To our knowledge, this is the largest soft tissue sarcoma of the chest wall reported in the literature. Postoperatively, the patient received 6 cycles of adjuvant chemotherapy.
Surgery is the mainstay of treatment, and chemotherapy and radiation are used in specific circumstances. Risk of recurrence is dependent on many factors, including histologic subtype, grade, and size of tumor. Long term surveillance with physical exam and imaging is recommended.
We feel that the multidisciplinary approach is crucial for optimal management of large soft tissue sarcomas. We recommend this approach to all patients with chest wall sarcomas.
PMCID: PMC5061302  PMID: 27721200
Thoracic surgery; Soft tissue sarcoma; Chest wall tumor; Case report
2.  Management of asymptomatic pulmonary vein aneurysm 
Aneurysm of a pulmonary vein is a rare vascular anomaly that is usually discovered incidentally as a pulmonary nodule or mediastinal mass. Most patients do not have any symptoms but some patients can present with dyspnea, hemoptysis, or cerebral thromboembolism. Proper diagnosis is crucial as to avoid unnecessary testing or surgical procedures. We highlight a case of an asymptomatic 59-year-old female with a pulmonary vein aneurysm presenting as a 1.5 cm right infrahilar nodule on contrast-enhanced CT during evaluation for acute cholecystitis. Further investigation with MRA revealed that it was vascular in nature, and pulmonary angiography showed dilation of the right inferior pulmonary vein with no communication to the pulmonary artery. On serial imaging, there has been no change in the size of the aneurysm. A small non-enlarging pulmonary vein aneurysm should be managed expectantly.
PMCID: PMC5099265  PMID: 27843764
Pulmonary venous aneurysm; Pulmonary vein varix; Pulmonary angiography
3.  Cervical Esophago-Gastric Tubes for Patients with Malignant Ascites 
Patients with chronic small bowel obstruction and malignant ascites from diffuse peritoneal carcinomatosis have limited options for gastrointestinal decompression as part of end-of-life palliation. Insertion of a percutaneous gastrostomy tube is relatively contraindicated in patients with ascites. Alternatively, nasogastric tube placement often leads to significant discomfort to patients and necessitates hospitalization during their last days of life. Here, we demonstrate how placing a percutaneous cervical esophago-gastric tube can allow adequate gastrointestinal decompression for terminal patients with malignant small bowel obstruction. This palliative measure allows them to remain in the comfort of their own homes after the procedure.
Electronic supplementary material
The online version of this article (doi:10.1007/s11605-016-3211-2) contains supplementary material, which is available to authorized users.
PMCID: PMC5187358  PMID: 27474099
Malignant small bowel obstruction; Palliative decompression; Quality of life
4.  Pseudoachalasia presenting 20 years after Nissen fundoplication: a case report 
Pseudoachalasia is a rare diagnosis manifested by clinical and physiologic symptoms of achalasia, with alternative etiology for outflow obstruction. While malignancy is a frequent cause of pseudoachalasia, prior surgical intervention especially surgery involving the esophagogastric junction, may result in a misdiagnosis of achalasia.
Case presentation
We present a case of a 70 year-old male with dysphagia and weight loss after undergoing a Billroth I and Nissen fundoplication several decades ago. His preoperative studies suggested achalasia and he was therefore referred for an endoscopic myotomy. However, careful interpretation of all the data and intra-operative findings revealed a classic mechanical and functional obstruction requiring takedown of his prior wrap.
Individualized interpretation of preoperative studies in the setting of prior foregut surgery is critical to appropriate diagnosis and intervention. This case highlights the significance of endoscopic findings and features of high-resolution manometry specific to pseudoachalasia, which contrasts with classical features of achalasia.
PMCID: PMC4936023  PMID: 27387670
Pseudoachalasia; Prior Nissen; High-resolution manometry
5.  Case report of using curved tip electrothermal bipolar coagulation to improve hilar dissection in VATS lobectomy 
•We describe use of 5 mm curved tip electrothermal bipolar sealing device in hilar dissection in video assisted thoracic surgery (VATS) lobectomy.•It allows complete dissection of hilar structures more easily during a VATS lobectomy for simple and complex hilum.
Thoracoscopic lobectomy has gained a pivotal role in the resection of lung cancer. To facilitate the minimally invasive approach, new surgical devices have been developed to help improve the feasibility of performing complex cases. Recently, we adopted the use of a 5 mm curved tip electrothermal bipolar sealing device.
Presentation of case
We highlight two patients with different type of hilum during VATS lobectomy. First patient had a peripheral lung cancer with simple hilum while second patient had bronchiectasis with very complex hilum. In both cases, use of 5 mm curved tip electrothermal bipolar sealing device helped in successful completion of video-assisted thoracoscopic lobectomy.
In these two cases, we were able to take advantage of the 5 mm curved tip electrothermal bipolar sealing device in completion of the hilar dissection.
Curved tip electrothermal bipolar sealing device allows complete dissection of hilar structures more easily during a lobectomy for simple and complex hilum. Use of this device may lead to more efficient VATS lobectomy.
PMCID: PMC4855748  PMID: 27100955
VATS, video assisted thoracic surgery; PET-CT, positron emission tomography-computed tomography; Lung cancer; Lobectomy; Video assisted thoracic surgery; Electrothermal bipolar coagulation; Case report
6.  Ex Vivo 4D Lung Cancer Model Mimics Metastasis 
The Annals of thoracic surgery  2015;99(4):1149-1156.
We have developed a 4D lung cancer model that forms perfusable tumor nodules. We determined if the model could be modified to mimic metastasis.
We modified the 4D lung cancer model by seeding H1299, A549, or H460 cells via the trachea only to the left lobes of the acellular lung matrix. The model was modified so that the tumor cells can reach the right lobes of the acellular lung matrix only through the pulmonary artery as circulating tumor cells (CTC). We determined the gene expressions of the primary tumor, CTCs, and metastatic lesions using the Human OneArray chip.
All cell lines formed a primary tumor in the left lobe of the ex vivo 4D lung cancer model. The CTCs were identified in the media and increased over time. All cell lines formed metastatic lesions with H460 forming significantly more metastatic lesions than H1299 and A549 cells. The CTC gene signature predicted poor survival in lung cancer patients. Unique genes were significantly expressed in CTC compared to the primary tumor and metastatic lesion.
The 4D lung cancer model can isolate tumor cells in three phases of tumor progression. This 4D lung cancer model may mimic the biology of lung cancer metastasis and may be used to determine its mechanism and potential therapy in the future.
PMCID: PMC4387006  PMID: 25701100
4D model; lung cancer; Metastasis
7.  Circulating Tumor Cells from 4D Model Have Less ITGB4 Expression 
The Journal of surgical research  2014;193(2):745-753.
Currently, there is no in vitro or ex vivo model that can isolate circulating tumor cells (CTCs). Recently, we developed a four-dimensional (4D) lung cancer model that allows for the isolation of CTCs. We postulated that these cells have different properties than parental (2D) cells.
Materials & Methods
We obtained CTCs by growing A549, H1299, 393P, and 344SQ cell lines on the 4D lung model. The CTCs were functionally characterized in vitro and gene expression of the cell adhesion molecules was compared with respective 2D cells. Integrin beta 4 (ITGB4) was further investigated by stably transfecting the A549 and H1299 cells.
We found that all cell lines produced CTCs and that CTCs from the 4D model were less adherent to the plastic and have a slower growth rate than respective 2D cells (p < 0.01). Most of the cell adhesion molecules were downregulated (p < 0.05) in CTCs, and ITGB4 was the common molecule, significantly more underexpressed in CTCs from all cell lines than their respective 2D cells. The modulation of ITGB4 led to a differential function of 2D cells.
CTCs from the 4D model have different transcriptional, translational, and in vitro characteristics than the same cells grown on a petri dish, and these CTCs from the 4D model have the properties of CTCs that are responsible for metastasis.
PMCID: PMC4268315  PMID: 25234746
4D model; ex vivo; lung cancer; circulating tumor cells
8.  Revision Breast Augmentation at the Time of Cardiac Sarcoma Resection: The Importance of Pocket Control When Inframammary Approach Is Combined with Simultaneous Sternotomy 
Supplemental Digital Content is available in the text.
Sternotomy in patients with previous breast augmentation becomes an aesthetic challenge when an inframammary approach is utilized over the traditional midline skin incision. Although the inframammary fold approach offers a well-concealed scar when compared with the midline chest incision, patients with a history of previous breast augmentation are at risk for alteration of the anatomy leading to symmastia, implant malposition, and asymmetry. We present a case report of sternotomy and resection of a mediastinal perivascular epithelioid cell tumor with concomitant revision augmentation with silicone implants and SERI Scaffold. Our patient had an uncomplicated postoperative course and a good cosmetic result 1 year after concomitant revision augmentation in conjunction with cardiac tumor resection. In conclusion, the authors feel that despite the difficulties in performing breast augmentation in patients undergoing thoracic surgery, it is possible to obtain good results. It is necessary to reinforce the repair with a mesh to recreate support and proper anatomy.
PMCID: PMC4874291  PMID: 27257577
9.  Endoscopic evaluation of gastric conduit perfusion in minimally invasive Ivor Lewis esophagectomy 
•Indocyanine green fluorescent imaging enables visualization of gastric conduit perfusion in real time.•Endoscopic ICG fluorescent imaging enables a minimally invasive assessment of gastric conduit perfusion and esophagectomy completion.•Minimally invasive esophagectomy using endoscopic ICG fluorescent imaging is a safe and time efficient procedure.
Laser-assisted indocyanine green (ICG) fluorescent dye angiography has been used in esophageal reconstructive surgery where it has been shown to significantly decrease the anastomotic leak rate. Recent advances in technology have made this possible in minimally invasive esophagectomy.
Presentation of case
We present a 69-year-old male with a cuT2N0M0 adenocarcinoma of the esophagus at the gastroesophageal junction who presented to our clinic after chemoradiation and underwent a minimally invasive Ivor Lewis esophagectomy. The perfusion of the gastric conduit was assessed intraoperatively using endoscopic ICG fluorescent imaging system. The anastomosis was created at the well-perfused site identified on the fluorescent imaging. The patient tolerated the procedure well, had an uneventful recovery going home on postoperative day 6 and tolerating a regular diet 2 weeks after the surgery.
Combination of minimally invasive surgery and endoscopic evaluation of perfusion of gastric conduit provide improved outcomes for surgical treatment for patients with esophageal cancer.
The gastric conduit during minimally invasive Ivor Lewis esophagectomy can be evaluated using endoscopic ICG fluorescent imaging.
PMCID: PMC4756224  PMID: 26745315
Minimally invasive esophagectomy; Indocyanine green; Laser angiography
10.  Three dimensional model for surgical planning in resection of thoracic tumors 
•3D printed model can be made of thoracic malignancy by taking CT image of the patient and creating a 3D surface rendered imaging and printing it on 3D printer.•3D printed model can help counsel the patient about the planned operation.•3D printed model can help in surgical planning of the resection of complex thoracic tumors.
The computed tomography scan provides vital information about the relationship of thoracic malignancies to the surrounding structures and aids in surgical planning. However, it can be difficult to visualize the images in a two-dimensional screen to interpret the full extent of the relationship between important structures in the surgical field.
Presentation of case
We report two cases where we used a three-dimensional printed model to aid in the surgical resection of thoracic malignancies.
Careful planning is necessary to resect thoracic malignancies. Although two-dimensional images of the thoracic malignancies provide vital information about the tumor and its surrounding structures, the three-dimensional printed model can provide more accurate information about the tumor and assist in surgical planning.
Three-dimensional printed model provide better visualization of complex thoracic tumors, aid in counseling the patient about the surgical procedure and assisted in surgical resection of thoracic malignancy.
PMCID: PMC4643475  PMID: 26453940
Pancoast tumor; Spindle cell neoplasm; 3D printed model; Surgical planning
11.  Human Lung Cancer Cells Grown on Acellular Rat Lung Matrix Create Perfusable Tumor Nodules 
The Annals of thoracic surgery  2012;93(4):1075-1081.
Extracellular matrix allows lung cancer to form its shape and grow. Recent studies on organ reengineering for orthotopic transplantation have provided a new avenue for isolating purified native matrix to use for growing cells. Whether human lung cancer cells grown in a decellularized rat lung matrix would create perfusable human lung cancer nodules was tested.
Rat lungs were harvested and native cells were removed using sodium dodecyl sulfate and Triton X-100 in a decellularization chamber to create a decellularized rat lung matrix. Human A549, H460, or H1299 lung cancer cells were placed into the decellularized rat lung matrix and grown in a customized bioreactor with perfusion of oxygenated media for 7 to 14 days.
Decellularized rat lung matrix showed preservation of matrix architecture devoid of all rat cells. All three human lung cancer cell lines grown in the bioreactor developed tumor nodules with intact vasculature. Moreover, the lung cancer cells developed a pattern of growth similar to the original human lung cancer.
Overall, this study shows that human lung cancer cells form perfusable tumor nodules in a customized bioreactor on a decellularized rat lung matrix created by a customized decellularization chamber. The lung cancer cells grown in the matrix had features similar to the original human lung cancer. This ex vivo model can be used potentially to gain a deeper understanding of the biologic processes involved in human lung cancer.
PMCID: PMC4512949  PMID: 22385822
12.  Gene Expression Profile of A549 Cells from Tissue of 4D Model Predicts Poor Prognosis in Lung Cancer Patients 
The tumor microenvironment plays an important role in regulating cell growth and metastasis. Recently, we developed an ex vivo lung cancer model (4D) that forms perfusable tumor nodules on a lung matrix that mimics human lung cancer histopathology and protease secretion pattern. We compared the gene expression profile (Human OneArray v5 chip) of A549 cells, a human lung cancer cell line, grown in a petri dish (2D), and of the same cells grown in the matrix of our ex vivo model (4D). Furthermore, we obtained gene expression data of A549 cells grown in a petri dish (2D) and matrigel (3D) from a previous study and compared the 3D expression profile with that of 4D. Expression array analysis showed 2,954 genes differentially expressed between 2D and 4D. Gene ontology (GO) analysis showed upregulation of several genes associated with extracellular matrix, polarity, and cell fate and development. Moreover, expression array analysis of 2D versus 3D showed 1006 genes that were most differentially expressed, with only 36 genes (4%) having similar expression patterns as observed between 2D and 4D. Finally, the differential gene expression signature of 4D cells (versus 2D) correlated significantly with poor survival in patients with lung cancer (n = 1,492), while the expression signature of 3D versus 2D correlated with better survival in lung cancer patients with lung cancer. Since patients with larger tumors have a worse rate of survival, the ex vivo 4D model may be a good mimic of natural progression of tumor growth in lung cancer patients.
PMCID: PMC4070715  PMID: 23934967
Lung cancer; matrigel; ex vivo 4D model; gene expression profile; survival
13.  Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma 
The Journal of Clinical Investigation  2015;125(3):1147-1162.
Epithelial tumor metastasis is preceded by an accumulation of collagen cross-links that heighten stromal stiffness and stimulate the invasive properties of tumor cells. However, the biochemical nature of collagen cross-links in cancer is still unclear. Here, we postulated that epithelial tumorigenesis is accompanied by changes in the biochemical type of collagen cross-links. Utilizing resected human lung cancer tissues and a p21CIP1/WAF1-deficient, K-rasG12D-expressing murine metastatic lung cancer model, we showed that, relative to normal lung tissues, tumor stroma contains higher levels of hydroxylysine aldehyde–derived collagen cross-links (HLCCs) and lower levels of lysine aldehyde–derived cross-links (LCCs), which are the predominant types of collagen cross-links in skeletal tissues and soft tissues, respectively. Gain- and loss-of-function studies in tumor cells showed that lysyl hydroxylase 2 (LH2), which hydroxylates telopeptidyl lysine residues on collagen, shifted the tumor stroma toward a high-HLCC, low-LCC state, increased tumor stiffness, and enhanced tumor cell invasion and metastasis. Together, our data indicate that LH2 enhances the metastatic properties of tumor cells and functions as a regulatory switch that controls the relative abundance of biochemically distinct types of collagen cross-links in the tumor stroma.
PMCID: PMC4362236  PMID: 25664850
14.  Esophageal cancer: Recent advances in screening, targeted therapy, and management 
The incidence of esophageal cancer remains on the rise worldwide and despite aggressive research in the field of gastrointestinal oncology, the survival remains poor. Much remains to be defined in esophageal cancer, including the development of an effective screening tool, identifying a good tumor marker for surveillance purposes, ways to target esophageal cancer stem cells as well as circulating tumor cells, and developing minimally invasive protocols to treat early-stage disease. The goal of this chapter is to highlight some of the recent advances and ongoing research in the field of esophageal cancer.
PMCID: PMC4229783  PMID: 25395880
Barrett's; cancer stem cells; carcinogenesis/tumorigenesis; dysplasia; esophageal cancer; targeted therapy
15.  Robot assisted thoracoscopic resection of giant esophageal leiomyoma 
•Esophageal leiomyoma is most common benign esophageal tumor.•Robot assisted surgery allows for resection of giant esophageal leiomyoma using minimally invasive approach.
Esophageal leiomyoma represents the most common benign esophageal tumor. Robot-assisted thoracoscopic surgery has provided ability to remove it successfully using a minimally invasive approach.
A 63-year old female with history of chronic chest pain presented with an esophageal mass on chest CT and endoscopic ultrasound. Robot-assisted surgery was performed using three robot arms, a camera and an assistant port. A 10 cm leiomyoma was enucleated and removed through a 2 cm myotomy. Completion endoscopy confirmed integrity of the esophagus. Patient's chest pain resolved postoperatively, and she was discharged on postoperative day 3.
Our case describes successful removal of the giant esophageal leiomyoma (10 cm) by robot assisted minimally invasive resection through a 2 cm myotomy.
Use of robot allows for removal of large esophageal leiomyoma. The improved dexterity and patient outcome offered by robot suggests its potential as the mainstay technique for giant esophageal leiomyoma removal.
PMCID: PMC4275859  PMID: 25460487
CT, computed tomography; Endo-GIA, endoscopic gastrointestinal automatic stapler; Esophageal leiomyoma; Robot assisted thoracoscopic surgery; Minimally invasive surgery
16.  Treatment of Sternoclavicular Joint Osteomyelitis with Debridement and Delayed Resection with Muscle Flap Coverage Improves Outcomes 
Surgery Research and Practice  2014;2014:747315.
The objective of this study was to evaluate the efficacy of various treatment options for sternoclavicular joint osteomyelitis. We evaluated patients with a diagnosis of sternoclavicular joint osteomyelitis, treated at our hospital from 2002 to 2012. Four treatment options were compared. Three out of twelve patients were successfully cured with antibiotics alone (25%). Debridement with or without negative pressure therapy was successful for one of three patients (33%). Simultaneous debridement, bone resection, and muscle flap coverage of the acquired defect successfully treated one of two patients (50%). Debridement with delayed bone resection and muscle flap coverage was successful in five of five patients (100%). Osteomyelitis of the sternoclavicular joint is a rare disease that has become more prevalent in recent years and can be associated with increasing use of long-term indwelling catheters. Initial debridement with delayed bone resection and pectoralis major muscle flap coverage can effectively treat sternoclavicular joint osteomyelitis.
PMCID: PMC4208504  PMID: 25379557
17.  Endoscopic management of Boerhaave's syndrome presenting with hematemesis 
Journal of Surgical Case Reports  2014;2014(11):rju110.
Hematemesis is an uncommon yet challenging presentation of Boerhaave's syndrome. Here, we present minimally invasive management of an esophageal perforation with hematemesis using esophageal stenting in an elderly male with multiple comorbidities.
PMCID: PMC4216456  PMID: 25362729
18.  AP2β nucleolar localization predicts poor survival after stage I non–small cell lung cancer resection 
The Annals of Thoracic Surgery  2011;92(3):1044-1050.
Activating enhancer-binding protein-2β (AP2β) is a transcription factor involved in apoptosis. The purpose of the current study was to assess the cellular location and level of AP2β in Non-Small Cell Lung Cancer (NSCLC) and normal lung tissue and investigate whether the level and localization of AP2β expression is predictive of overall survival in patients with stage I NSCLC.
We performed immunohistochemical analysis of tissue microarrays (TMAs) prepared from stage I NSCLC specimens with adjacent normal lung tissue from two independent sets of patients who underwent lung resection with curative intent at our institution. AP2β intensity was assessed in TMAs, and AP2β staining patterns were classified as either diffuseor nucleolar in the TMAs. AP2β intensity and localization were analyzed for correlation with patients' survival.
Immunohistochemical analysis of TMAs showed that the intensity of AP2β immunohistochemical staining did not correlate with overall survival. When location of AP2β was analyzed in TMAs, all of the normal lung tissue had diffuse pattern of AP2β. In the first set of NSCLC, patients with nucleolar pattern had a significantly lower 5-year survival rate than patients with diffuse pattern (67% vs. 100%; P = 0.004); this finding was confirmed in the second set (64% vs. 91%; P = 0.02). Multivariate analysis revealed that nucleolar pattern was an independent predictor of poor overall survival in both sets.
The AP2β which is located in the nucleoplasm in normal lung tissue is found in either nucleoplasm or nucleoli in NSCLC. The patients with AP2β in the nucleoli had poor survival compared to patients with AP2β in the cytoplasm.
PMCID: PMC3272351  PMID: 21871297
Lung cancer biology; survival analysis
19.  Acute Shingles after Resection of Thoracic Schwannoma 
Texas Heart Institute Journal  2012;39(2):265-267.
Herpes zoster is relatively uncommon after surgery in immunocompetent patients. To our knowledge, there have been no reports of herpes zoster after the resection of a thoracic schwannoma. We report the case of a 48-year-old woman in whom acute shingles developed after the video-assisted thoracic surgical resection of a posterior mediastinal schwannoma adjacent to the 4th thoracic vertebral body. The patient recovered after receiving timely antiviral therapy.
Rash and pain are common in patients who have wound infections and contact dermatitis after surgery, so the possible reactivation of varicella virus might not be prominent in the surgeon's mind. This case serves as a reminder that viral infections such as shingles should be considered in the differential diagnosis of postoperative erythema and pain.
PMCID: PMC3384061  PMID: 22740749
Diagnosis, differential; herpes zoster/diagnosis/epidemiology/etiology; postoperative complications; skin diseases, viral/diagnosis/drug therapy; thoracic surgery, video-assisted; virus activation
20.  Fibulin-2 Is a Driver of Malignant Progression in Lung Adenocarcinoma 
PLoS ONE  2013;8(6):e67054.
The extracellular matrix of epithelial tumors undergoes structural remodeling during periods of uncontrolled growth, creating regional heterogeneity and torsional stress. How matrix integrity is maintained in the face of dynamic biophysical forces is largely undefined. Here we investigated the role of fibulin-2, a matrix glycoprotein that functions biomechanically as an inter-molecular clasp and thereby facilitates supra-molecular assembly. Fibulin-2 was abundant in the extracellular matrix of human lung adenocarcinomas and was highly expressed in tumor cell lines derived from mice that develop metastatic lung adenocarcinoma from co-expression of mutant K-ras and p53. Loss-of-function experiments in tumor cells revealed that fibulin-2 was required for tumor cells to grow and metastasize in syngeneic mice, a surprising finding given that other intra-tumoral cell types are known to secrete fibulin-2. However, tumor cells grew and metastasized equally well in Fbln2-null and -wild-type littermates, implying that malignant progression was dependent specifically upon tumor cell-derived fibulin-2, which could not be offset by other cellular sources of fibulin-2. Fibulin-2 deficiency impaired the ability of tumor cells to migrate and invade in Boyden chambers, to create a stiff extracellular matrix in mice, to cross-link secreted collagen, and to adhere to collagen. We conclude that fibulin-2 is a driver of malignant progression in lung adenocarcinoma and plays an unexpected role in collagen cross-linking and tumor cell adherence to collagen.
PMCID: PMC3677922  PMID: 23785517
21.  Human Lung Cancer Cells Grown in an Ex Vivo 3D Lung Model Produce Matrix Metalloproteinases Not Produced in 2D Culture 
PLoS ONE  2012;7(9):e45308.
We compared the growth of human lung cancer cells in an ex vivo three-dimensional (3D) lung model and 2D culture to determine which better mimics lung cancer growth in patients. A549 cells were grown in an ex vivo 3D lung model and in 2D culture for 15 days. We measured the size and formation of tumor nodules and counted the cells after 15 days. We also stained the tissue/cells for Ki-67, and Caspase-3. We measured matrix metalloproteinase (MMP) levels in the conditioned media and in blood plasma from patients with adenocarcinoma of the lung. Organized tumor nodules with intact vascular space formed in the ex vivo 3D lung model but not in 2D culture. Proliferation and apoptosis were greater in the ex vivo 3D lung model compared to the 2D culture. After 15 days, there were significantly more cells in the 2D culture than the 3D model. MMP-1, MMP-9, and MMP-10 production were significantly greater in the ex vivo 3D lung model. There was no production of MMP-9 in the 2D culture. The patient samples contained MMP-1, MMP-2, MMP-9, and MMP-10. The human lung cancer cells grown on ex vivo 3D model form perfusable nodules that grow over time. It also produced MMPs that were not produced in 2D culture but seen in human lung cancer patients. The ex vivo 3D lung model may more closely mimic the biology of human lung cancer development than the 2D culture.
PMCID: PMC3444466  PMID: 23028922
22.  Chlamydia pneumoniae Enhances Cytokine-Stimulated Human Monocyte Matrix Metalloproteinases through a Prostaglandin E2-Dependent Mechanism  
Infection and Immunity  2005;73(1):632-634.
Exposure of human monocytes to Chlamydia pneumoniae resulted in a significant enhancement of matrix metalloproteinase (MMP) 1 and 9 production following stimulation with tumor necrosis factor alpha and granulocyte monocyte-colony stimulating factor. The effect of C. pneumoniae on monocyte MMPs was mediated through the induction of prostaglandin E2. These findings may have implications for atherosclerotic plaque rupture.
PMCID: PMC538927  PMID: 15618206

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