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Old 01-13-2010, 10:15 AM   #1
Rich66
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Join Date: Feb 2008
Location: South East Wisconsin
Posts: 3,431
Lung mets

(cryotherapy, radiofrequency ablation/RFA, microwave, laser, aerosolized chemo, w/cyclo, w/vit D)



Overview of ablation techniques: http://www.cancerablation.com/procedures.html



Cancer Imaging. 2008 Apr 22;8:116-7.
Lung tumour ablation - where are we now?

Gillams A.



Abstract

Ablation of lung tumours is the fastest expanding area within interventional oncology. Radiofrequency, laser, microwave and cryotherapy have all been shown to be effective. Which of these ablation technologies becomes the preferred technique for lung tumours remains to be seen.

PMID: 18442957 [PubMed - indexed for MEDLINE]PMCID: PMC2365456Free PMC Article



Ann Surg Oncol. 2009 Dec 22. [Epub ahead of print]
Rate of Freeze Alters the Immunologic Response After Cryoablation of Breast Cancer.

Sabel MS, Su G, Griffith KA, Chang AE.
Division of Surgical Oncology, University of Michigan, Ann Arbor, MI, USA, msabel@umich.edu.
BACKGROUND: Cryoablation has garnered significant interest as a treatment for solid tumors including breast cancer for both its local effects and potential in stimulating an antitumor immune response. We sought to examine the impact that variances in technique might have on the immune response and examine the mechanism by which cryoablation may stimulate an antitumor immune response. MATERIALS AND METHODS: Balb/c mice with established 4T1 mammary carcinomas were treated by cryoablation at either a high rate of freeze or low rate of freeze, or by surgical excision, after spontaneous metastases occurred. Tumor-draining lymph nodes (TDLN) were excised at 1 week for EliSPOT assay and immunophenotyping. Mice were followed after treatment for enumeration of pulmonary metastases and survival. RESULTS: Compared with surgical excision, cryoablation using a high freeze rate resulted in a significant increase in tumor-specific T cells in the TDLN, a reduction in pulmonary metastases, and improved survival. However, cryoablation using a low freeze rate resulted in an increase in regulatory T cells, a significant increase in pulmonary metastases, and decreased survival. CONCLUSIONS: Cryoablation of breast cancer in mice can generate a tumor-specific immune response that can eradicate systemic micrometastases and improve outcome compared with surgical excision; however, the technique used to freeze the tissue may alter the immune response from stimulatory to suppressive.

PMID: 20033323 [PubMed - as supplied by publisher]




Freezing Breast Tumors Helps Stop Cancer's Spread In Mice

03 Mar 2010


LINK
Freezing a cancer kills it in its place, and also appears to generate an immune response that helps stop the cancer's spread, leading to improved survival rates over surgery, according to a new study in mice from researchers at the University of Michigan Comprehensive Cancer Center.

Quote:
Researchers looked at two different cryoablation techniques, which both involve applying a cold probe to a tumor to freeze it. The study was done in mice with breast cancer. One method involves freezing the tumor rapidly, in about 30 seconds; the other freezes the tumor slowly, taking a few minutes.
Quote:
Both cryoablation techniques successfully killed the breast tumor. The mice treated with the rapid freeze had fewer tumors that spread to the lungs and improved survival compared to mice treated with surgery alone or mice treated with the slower freezing technique. The study showed that the benefit from the rapid freezing is likely due to changes in the immune system that help to kill the tumor. Freezing with the slower technique appeared to make the immune system not as able to kill the tumor.
Quote:
The study showed that the benefit from the rapid freezing is likely due to changes in the immune system that help to kill the tumor. Freezing with the slower technique appeared to make the immune system not as able to kill the tumor.
Quote:
"Cryoablation has strong potential as a treatment for breast cancer. Not only does it appear effective in treating the primary tumor with little cosmetic concerns, but it also may stimulate an immune response capable of eradicating any cells that have traveled throughout the body, reducing both local and distant recurrence, similar to giving a breast cancer vaccine," says lead study author Michael Sabel, M.D., associate professor of surgery at the U-M Medical School.
]


Cancer Cell. 2009 Aug 4;16(2):91-102.
CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages.

DeNardo DG, Barreto JB, Andreu P, Vasquez L, Tawfik D, Kolhatkar N, Coussens LM.
Department of Pathology, University of California, San Francisco, CA 94143, USA.
Comment in:
FREE TEXT
During breast cancer development, increased presence of leukocytes in neoplastic stroma parallels disease progression; however, the functional significance of leukocytes in regulating protumor versus antitumor immunity in the breast remains poorly understood. Utilizing the MMTV-PyMT model of mammary carcinogenesis, we demonstrate that IL-4-expressing CD4(+) T lymphocytes indirectly promote invasion and subsequent metastasis of mammary adenocarcinomas by directly regulating the phenotype and effector function of tumor-associated CD11b(+)Gr1(-)F4/80(+) macrophages that in turn enhance metastasis through activation of epidermal growth factor receptor signaling in malignant mammary epithelial cells. Together, these data indicate that antitumor acquired immune programs can be usurped in protumor microenvironments and instead promote malignancy by engaging cellular components of the innate immune system functionally involved in regulating epithelial cell behavior.



PMID: 19647220 [PubMed - indexed for MEDLINE]


Cardiovasc Intervent Radiol. 2010 May 1. [Epub ahead of print]
Optimizing the Protocol for Pulmonary Cryoablation: A Comparison of a Dual- and Triple-Freeze Protocol.

Hinshaw JL, Littrup PJ, Durick N, Leung W, Lee FT Jr, Sampson L, Brace CL.
Department of Radiology, University of Wisconsin, Mail Code 3252, 600 Highland Ave., Madison, WI, 53792-3252, USA, jhinshaw@uwhealth.org.
Abstract

The purpose of this study was to compare a double freeze-thaw protocol to a triple freeze-thaw protocol for pulmonary cryoablation utilizing an in vivo porcine lung model. A total of 18 cryoablations were performed in normal porcine lung utilizing percutaneous technique with 9 each in a double- (10-5-10) and triple-freeze (3-3-7-7-5) protocol. Serial noncontrast CT images were obtained during the ablation. CT imaging findings and pathology were reviewed. No imaging changes were identified during the initial freeze cycle with either protocol. However, during the first thaw cycle, a region of ground glass opacity developed around the probe with both protocols. Because the initial freeze was shorter with the triple freeze-thaw protocol, the imaging findings were apparent sooner with this protocol (6 vs. 13 min). Also, despite a shorter total freeze time (15 vs. 20 min), the ablation zone identified with the triple freeze-thaw protocol was not significantly different from the double freeze-thaw protocol (mean diameter: 1.67 +/- 0.41 cm vs. 1.66 +/- 0.21 cm, P = 0.77; area: 2.1 +/- 0.48 cm(2) vs. 1.99 +/- 0.62 cm(2), P = 0.7; and circularity: 0.95 +/- 0.04 vs. 0.96 +/- 0.03, P = 0.62, respectively). This study suggests that there may be several advantages of a triple freeze-thaw protocol for pulmonary cryoablation, including earlier identification of the imaging findings associated with the ablation, the promise of a shorter procedure time or larger zones of ablation, and theoretically, more effective cytotoxicity related to the additional freeze-thaw cycle.

PMID: 20437048 [PubMed - as supplied by publisher]




J Pharmacol Exp Ther. 2009 Aug;330(2):596-601. Epub 2009 Apr 30.
Cyclophosphamide unmasks an antimetastatic effect of local tumor cryoablation.

Levy MY, Sidana A, Chowdhury WH, Solomon SB, Drake CG, Rodriguez R, Fuchs EJ.
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

  1. Address correspondence to:
    Dr. Ephraim J. Fuchs, 488 Bunting-Blaustein Cancer Research Building, 1650 Orleans Street, Baltimore, MD 21231. E-mail: fuchsep@jhmi.edu

Abstract

Cryoablation of a solitary tumor mass releases intact tumor antigens and can induce protective antitumor immunity but has limited efficacy in the treatment of established metastatic cancer. Cyclophosphamide (Cy), an anticancer drug, selectively depletes regulatory T cells (Tregs) and attenuates suppression of antitumor immunity. We used a BALB/c mouse model of metastatic colon cancer to investigate the systemic antitumor effects of in situ cryotherapy alone or in combination with 200 mg/kg i.p. Cy. When combined with Cy, cryoablation was significantly more effective than either surgical excision or cautery at inducing systemic antitumor immunity, resulting in the cure of a fraction of animals with established metastatic disease and resistance to tumor rechallenge. Lymphocytes from cured animals contained an expanded population of tumor-specific, interferon-γ producing T cells and transferred antitumor immunity to naive recipients. Depletion of CD8+ cells significantly impaired the adoptive transfer of antitumor immunity. Furthermore, treatment with Cy and cryoablation was associated with a significant decrease in the ratio of regulatory to effector CD4+ T cells. The combination of tumor cryoablation and Cy induces potent, systemic antitumor immunity in animals with established metastatic disease.



Cryobiology. 1983 Feb;20(1):78-82.
Cyclophosphamide pretreatment in tumor cryotherapy: a comparison with alternative drugs.

Cooper AJ, Fraser JD.
Abstract

The method of Turk and Lagrange for modulating immune responses in favor of the cell-mediated effector arm by using single high doses of cyclophosphamide 3 days before antigen has previously been shown to cause decreased rates of local tumor recurrence when adapted as an adjunctive therapy to cryosurgery in a murine model. This series of experiments compares cyclophosphamide, azathioprine, and methotrexate against cryosurgery alone in the same therapeutic protocol. Only cyclophosphamide gave enhanced numbers of cures; azathioprine caused an increase in metastases arising concurrently with local tumor recrudescence.

PMID: 6831912 [PubMed - indexed for MEDLINE]






Letrozole (Femara) alone or with Cyclophosphamide decrease Tregs, possibly helpful to Crotherapy, even in ER- tumors:

Clin Cancer Res. 2009 Feb 1;15(3):1046-51.
Immunomodulation of FOXP3+ regulatory T cells by the aromatase inhibitor letrozole in breast cancer patients.

Generali D, Bates G, Berruti A, Brizzi MP, Campo L, Bonardi S, Bersiga A, Allevi G, Milani M, Aguggini S, Dogliotti L, Banham AH, Harris AL, Bottini A, Fox SB.
Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.

FREE TEXT


Abstract

PURPOSE: We have shown previously that tumor infiltration by FOXP3+ regulatory T cells (Treg) is associated with increased relapse and shorter survival of patients with both in situ and invasive breast cancer. Because estrogen regulates Treg numbers in mice and promotes the proliferation of human Tregs, we hypothesized that blocking estrogen receptor-alpha signaling would abrogate Tregs and be associated with response to hormonal therapy and increased survival. EXPERIMENTAL DESIGN: FOXP3+ Tregs were quantified in tumor samples collected at baseline by incisional biopsy and after 6 months at definitive surgery in 83 elderly breast cancer patients (T2-4 N0-1) enrolled in a randomized phase II trial based on 6 months of primary letrozole (2.5 mg/d) or 6 months of letrozole plus oral "metronomic" cyclophosphamide (50 mg/d). RESULTS: Treg number ranged from 0 to 380 (median, 30) before treatment and from 0 to 300 (median, 8) after treatment. There was a significant reduction in Tregs in letrozole and letrozole-cyclophosphamide patients (P < 0.0001 and P < 0.002, respectively) after treatment. Treg number at residual histology was inversely related with response (P < 0.03 and P = 0.50, respectively) and a greater Treg reduction was observed in responding patients (P < 0.03). CONCLUSION: This study suggests that aromatase inhibitors may have an indirect antitumor mechanism of action through reducing Tregs in breast tumors and may be of use in estrogen receptor-alpha-negative tumors in combination with immunotherapy approaches.

PMID: 19188178 [PubMed - indexed for MEDLINE]Free Article


Quote:
Translational Relevance We have shown recently that high numbers of Tregs in in situ and invasive breast carcinomas give independent prognostic information even beyond 5 years when conventional pathologic factors lose their power. Because Tregs play a pivotal role in immunosuppression and tumor emergence, we performed a phase II randomized controlled trial of letrozole ± the immunomodulatory agent cyclophosphamide in breast cancer patients to assess the clinical utility of the number of Tregs in predicting the response to therapy. This question addresses second of the top 15 breast cancer research priorities determined by registrants at the San Antonio Breast and St Gallen meetings in 2005. We show a significant reduction in the numbers of Tregs in the primary tumor after treatment with an aromatase inhibitor but not by the addition of cyclophosphamide, showing that the effect is largely due to the aromatase inhibitor. Importantly, this reduction in Tregs is inversely related to the response. These novel findings suggest that letrozole has a significant immunomodulatory role and that aromatase inhibitors could be used in the future in combination with other immunotherapeutic approaches not only in patients with ER-positive but also in ER-negative tumors.



Urology. 2010 Jul 2. [Epub ahead of print]
Role of Vitamin D(3) as a Sensitizer to Cryoablation in a Murine Prostate Cancer Model: Preliminary In Vivo Study.

Kimura M, Rabbani Z, Mouraviev V, Tsivian M, Caso J, Satoh T, Baba S, Vujaskovic Z, Baust JM, Baust JG, Polascik TJ.
Duke Prostate Center and Division of Urologic Surgery, Department of Surgery, Durham, North Carolina.
Abstract

OBJECTIVES: Calcitriol has been reported to have antitumor efficacy in several cancers. In this study, we hypothesized that calcitriol may potentially function as a cryosensitizer that can enhance cryoablation, and we investigated several molecular marker changes in a murine model of prostate cancer. METHODS: Murine prostate tumors (RM-9) were grown in male C57BL/6J mice subcutaneously with neoadjuvant intratumoral injection of calcitriol followed by cryoablation. The microenvironmental changes after cryoablation alone and in combination with calcitriol were analyzed in a comparative fashion using immunohistochemistry and Western blot analyses. RESULTS: Both cryoablation and the combination group could suppress tumor growth after treatment compared with the control. At final pathologic assessment, a larger necrotic area was seen in the combination group (P = .026). Although microvessel density (CD31) and the area of hypoxia (pimonidazole) was not different between the control and combination groups, cell proliferation (Ki-67) significantly decreased in the combination treatment (P = .035). In Western blot analyses, several markers for apoptosis were expressed significantly higher with the combination treatment. CONCLUSIONS: The synergistic effect of calcitriol with cryoablation was demonstrated because of enhanced antitumor efficacy by increasing necrosis and apoptosis and reduced cell proliferation. This study suggests that calcitriol is a potentially applicable reagent as a freeze sensitizer to cryoablation. Copyright © 2010 Elsevier Inc. All rights reserved.

PMID: 20599255 [PubMed - as supplied by publisher]




Intern Med. 2010;49(5):431-3. Epub 2010 Mar 1.
Acute respiratory distress syndrome after percutaneous cryotherapy for a pulmonary metastatic lesion.

Tasaka S, Tomomatsu K, Funatsu Y, Soejima K, Ishizaka A.
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo. tasaka@cpnet.med.keio.ac.jp

Abstract

Percutaneous cryotherapy (PCT) under computed tomographic guidance is minimally invasive, with satisfactory local control of primary lung cancer and pulmonary metastatic lesions. We report a case of acute respiratory distress syndrome (ARDS) in a patient who underwent PCT for lung metastasis of recurrent esophageal cancer. The patient responded to pulse steroid therapy and recovered from severe respiratory failure. Excessive inflammatory response to necrotic debris might contribute to the development of ARDS. To the best of our knowledge, this is the first report describing the details of ARDS following PCT.

PMID: 20190478 [PubMed - indexed for MEDLINE]Free Article




Eur J Cancer. 2009 Jul;45(10):1773-9. Epub 2009 Mar 11.
The use of PTC and RFA as treatment alternatives with low procedural morbidity in non-small cell lung cancer.

Choe YH, Kim SR, Lee KS, Lee KY, Park SJ, Jin GY, Lee YC.
Department of Internal Medicine and Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Jeonju, Jeonbuk, South Korea.
Abstract

Minimally invasive percutaneous ablative therapies for treating lung cancers are currently being studied as treatment alternatives. This present study investigated the efficacies of percutaneous thoracic cryotherapy (PTC) and radiofrequency ablation (RFA) on clinical courses of pulmonary malignant tumours, especially in the setting of non-surgical candidates. Sixty-five patients with lung malignancy underwent sixty-seven sessions of RFA and nine sessions of PTC. We evaluated the results of RFA and PTC including efficacies, local progression rate, survival rate, and complications. Twenty-nine patients (43.3%) treated with RFA and six patients (66.7%) with PTC attained complete ablation. In small-sized lung mass (3 cm), complete ablation rate of RFA and PTC was increased to 76.2% and 85.7%, respectively. Additionally, we have found that the complete ablation group had significantly higher survival duration and progression free survival duration compared with the partial ablation group. Moreover, the complication profile was acceptable and the pain associated with the procedures disappeared within 1 day; 42 patients (62.7%) after RFA and all patients after PTC. This study provides evidence for the use of PTC and RFA as treatment alternatives with low procedural morbidity in the management of inoperable pulmonary malignant tumours, although the current study is limited by the small sample size and the short follow-up period.

PMID: 19285385 [PubMed - indexed for MEDLINE]




Cardiovasc Intervent Radiol. 2010 Apr 29. [Epub ahead of print]
Lung Tumor Radiofrequency Ablation: Where Do We Stand?

de Baère T.
Department of Interventional Radiology, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805, Villejuif, France, debaere@igr.fr.
Abstract

Today, radiofrequency ablation (RFA) of primary and metastatic lung tumor is increasingly used. Because RFA is most often used with curative intent, preablation workup must be a preoperative workup. General anesthesia provides higher feasibility than conscious sedation. The electrode positioning must be performed under computed tomography for sake of accuracy. The delivery of RFA must be adapted to tumor location, with different impedances used when treating tumors with or without pleural contact. The estimated rate of incomplete local treatment at 18 months was 7% (95% confidence interval, 3-14) per tumor, with incomplete treatment depicted at 4 months (n = 1), 6 months (n = 2), 9 months (n = 2), and 12 months (n = 2). Overall survival and lung disease-free survival at 18 months were, respectively, 71 and 34%. Size is a key point for tumor selection because large size is predictive of incomplete local treatment and poor survival. The ratio of ablation volume relative to tumor volume is predictive of complete ablation. Follow-up computed tomography that relies on the size of the ablation zone demonstrates the presence of incomplete ablation. Positron emission tomography might be an interesting option. Chest tube placement for pneumothorax is reported in 8 to 12%. Alveolar hemorrhage and postprocedure hemoptysis occurred in approximately 10% of procedures and rarely required specific treatment. Death was mostly related to single-lung patients and hilar tumors. No modification of forced expiratory volume in the first second between pre- and post-RFA at 2 months was found. RFA in the lung provides a high local efficacy rate. The use of RFA as a palliative tool in combination with chemotherapy remains to be explored.

PMID: 20429003 [PubMed - as supplied by publisher]




Eur J Radiol. 2010 May 7. [Epub ahead of print]
Radiofrequency ablation of pulmonary tumors.

Crocetti L, Lencioni R.
Division of Diagnostic Imaging and Intervention, Department of Liver Transplants, Hepatology and Infectious Diseases, Pisa University School of Medicine, Italy.
Abstract

The development of image-guided percutaneous techniques for local tumor ablation has been one of the major advances in the treatment of solid tumors. Among these methods, radiofrequency (RF) ablation is currently established as the primary ablative modality at most institutions. RF ablation is accepted as the best therapeutic choice for patients with early-stage hepatocellular carcinoma when liver transplantation or surgical resection are not suitable options and is considered as a viable alternate to surgery for inoperable patients with limited hepatic metastatic disease, especially from colorectal cancer. Recently, RF ablation has been demonstrated to be a safe and valuable treatment option for patients with unresectable or medically inoperable lung malignancies. Resection should remain the standard therapy for non-small cell lung cancer (NSCLC) but RF ablation may be better than conventional external-beam radiation for the treatment of the high-risk individual with NSCLC. Initial favourable outcomes encourage combining radiotherapy and RF ablation, especially for treating larger tumors. In the setting of colorectal cancer lung metastases, survival rates provided by RF ablation in selected patients, are substantially higher than those obtained with any chemotherapy regimens and provide indirect evidence that RF ablation therapy improves survival in patients with limited lung metastatic disease. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

PMID: 20452739 [PubMed - as supplied by publisher]






Interact Cardiovasc Thorac Surg. 2010 Apr;10(4):650-1. Epub 2010 Jan 26.
Parietal tumor recurrence of lung metastasis after radiofrequency ablation.

Guihaire J, Verhoye JP, de Latour B, Leguerrier A.
Department of Cardiovascular and Thoracic Surgery, Pontchaillou Hospital, Rennes, France.



Abstract

Metastasis is the most common form of malignant lung tumor. Radiofrequency ablation (RFA) is a new treatment for single pulmonary tumors. However, RFA can be complicated by iatrogenic and parietal recurrence. We report the case of a 67-year-old man with a single pulmonary metastasis from colorectal cancer diagnosed two years previously and locally controlled by left hemi-colectomy. The metastasis was treated by RFA. Four months after the procedure, a positron emission tomography scan revealed parietal chest contamination. Surgical resection enabled the diagnosis of parietal tumor expansion and confirmed successful treatment of the initial metastasis. This case highlights the risk of iatrogenic parietal contamination after RFA. To our knowledge no similar case has been published to date. The most appropriate steps to prevent this type of complication still have to be defined.
PMID: 20103508 [PubMed - in process]Free Article




J Transl Med. 2010 Jul 29;8:73.
Low temperature of radiofrequency ablation at the target sites can facilitate rapid progression of residual hepatic VX2 carcinoma.

Ke S, Ding XM, Kong J, Gao J, Wang SH, Cheng Y, Sun WB.
Department of Hepatobiliary Surgery, West Campus, Beijing Chao-yang Hospital Affiliated to Capital Medical University, Beijing 100043, China.


FREE TEXT

Abstract

BACKGROUND: Rapid progression of residual tumor after radiofrequency ablation (RFA) of hepatocellular carcinoma has been observed increasingly. However, its underlying mechanisms remain to be clarified. The present study was designed to determine whether low temperature of RFA at the target sites facilitates rapid progression of residual hepatic VX2 carcinoma and to clarify the possible underlying mechanisms.
METHODS: The residual VX2 hepatoma model in rabbits was established by using RFA at 55, 70 and 85 degrees C. Rabbits that were implanted with VX2 hepatoma but did not receive RFA acted as a control group. The relationship between rapid progression of residual hepatic VX2 carcinoma and low temperature of RFA at the target sites was carefully evaluated. A number of potential contributing molecular factors, such as proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 9 (MMP-9), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and Interleukin-6 (IL-6) were measured.
RESULTS: The focal tumor volume and lung metastases of RFA-treated rabbits increased significantly compared with the control group (P < 0.05), and the greatest changes were seen in the 55 degrees C group (P < 0.05). Expression of PCNA, MMP-9, VEGF, HGF and IL-6 in tumor tissues increased significantly in the RFA-treated groups compared with the control group, and of the increases were greatest in the 55 degrees C group (P < 0.05). These results were consistent with gross pathological observation. Tumor re-inoculation experiments confirmed that low temperature of RFA at the target sites facilitated rapid progression of residual hepatic VX2 carcinoma.
CONCLUSIONS: Insufficient RFA that is caused by low temperature at the target sites could be an important cause of rapid progression of residual hepatic VX2 carcinoma. Residual hepatic VX2 carcinoma could facilitate its rapid progression through inducing overexpression of several molecular factors, such as PCNA, MMP-9, VEGF, HGF and IL-6.

PMID: 20667141 [PubMed - in process]PMCID: PMC2917410Free PMC Article







J Aerosol Med Pulm Drug Deliv. 2008 Mar;21(1):61-70.
Aerosolized chemotherapy.

Gagnadoux F, Hureaux J, Vecellio L, Urban T, Le Pape A, Valo I, Montharu J, Leblond V, Boisdron-Celle M, Lerondel S, Majoral C, Diot P, Racineux JL, Lemarie E.
Département de Pneumologie, CHU, Angers, France. frgagnadoux@chu-angers.fr
Regional chemotherapy has been proposed as a treatment modality in a number of cancer settings. In primary or metastatic lung cancer, administration of chemotherapy via inhalation could increase exposure of lung tumor to the drug, while minimizing systemic side effects. Several proof of concept studies in animal models of metastatic or primary lung cancer have demonstrated the safety, pharmacokinetic advantage, and antitumor effect of aerosol administration of several chemotherapeutic agents including doxorubicin, gemcitabine and liposome-encapsulated formulations of paclitaxel and 9-nitrocamptothecin (9-NC). Recent phase I studies have demonstrated the feasibility of aerosol delivery of doxorubicin and liposomal formulations of 9-NC and cisplatin in patients with primary and metastatic lung cancer with a limited pharmacokinetic profile consistent with the observed low systemic toxicity. Further studies integrating safety, pharmacokinetic, and efficacy considerations are required to determine whether there is a place for local administration of chemotherapy via inhalation in lung cancer.

PMID: 18518832 [PubMed - indexed for MEDLINE]



Cancer. 1987 Feb 15;59(4):688-9.
Nasally administered buserelin inducing complete remission of lung metastases in male breast cancer.

Vorobiof DA, Falkson G.
A 60-year-old man with bilateral lung metastases from breast cancer was treated with the gonadotropin-releasing hormone analogue, buserelin, given as an intranasal spray. Androgen deprivation and complete remission of lung metastases were achieved with minimal side effects. Androgen deprivation by means of nasally administered buserelin offers an easy and efficient alternate approach in the treatment of metastatic male breast cancer.

PMID: 3100015 [PubMed - indexed for MEDLINE]


Cancer Treat Res. 2010;152:203-15.
Non-Surgical Treatment of Pulmonary and Extra-pulmonary Metastases.

Anderson P.
Children's Cancer Hospital, University of Texas MD Anderson Cancer Center, Unit 87, Pediatrics, 1515 Holcombe Blvd., Houston, TX, 77030-4009, USA, pmanders@mdanderson.org.
Studies have demonstrated that chemotherapy alone is usually unsuccessful as exclusive therapy for osteosarcoma (Cancer 95:2202-2201, 2002). Information will be presented for situations where non-surgical alternatives could be considered as useful, if not necessary, adjuncts to chemotherapy. In the thorax these include treatment of pleural effusions, chest wall lesions, central lung or mediastinal osteosarcoma, as well as recurrences in patients with limited pulmonary reserve. Other situations include too many metastases to easily resect, axial osteosarcomas, bone metastases, liver and brain metastases.Non-surgical local control measures include radiation with chemotherapy for radiosensitization, bone-seeking radioisotopes (e.g., (153)Sm-EDTMP, (223)Ra), bisphosphonates, heat (radiofrequency ablation), freezing and thawing (cryoablation), and intracavitary or regional (aerosol) therapy. Because of the predictable and common pattern of pulmonary metastases in osteosarcoma, aerosol therapy also offers an attractive regional treatment strategy. Principles and use of aerosol cytokines (e.g., GM-CSF, IL-2), and aerosol chemotherapy with gemcitabin will be discussed. Individual cases illustrating strategy and techniques will be presented.

PMID: 20213392 [PubMed - in process]




Cardiovasc Intervent Radiol. 2010 Mar 16. [Epub ahead of print]
Bronchopleural Fistula After Radiofrequency Ablation of Lung Tumours.

Cannella M, Cornelis F, Descat E, Ferron S, Carteret T, Castagnède H, Palussière J.
Department of Interventional Radiology, Institut Bergonié, Regional Cancer Center, 229 cours de l'Argonne, 33076, Bordeaux Cedex, France.
The present article describes two cases of bronchopleural fistula (BPF) occurring after radiofrequency ablation of lung tumors. Both procedures were carried out using expandable multitined electrodes, with no coagulation of the needle track. After both ablations, ground-glass opacities encompassed the nodules and abutted the visceral pleura. The first patient had a delayed pneumothorax, and the second had a recurrent pneumothorax. Both cases of BPF were diagnosed on follow-up computed tomography chest scans (i.e., visibility of a distinct channel between the lung or a peripheral bronchus and the pleura) and were successfully treated with chest tubes alone. Our goal is to highlight the fact that BPF can occur without needle-track coagulation and to suggest that minimally invasive treatment is sufficient to cure BPFs of this specific origin.

PMID: 20232201 [PubMed - as supplied by publisher]
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Old 05-16-2010, 11:32 PM   #2
Rich66
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Re: Lung mets

(in research)

http://medicalphysicsweb.org/cws/article/research/39057

May 13, 2009
Microwave ablation best for lung tumours

Microwave ablation of lung tumours outperforms the more established radiofrequency (RF) ablation technique, according to a new animal study published in Radiology from the University of Wisconsin.
Analysis of gross pathology and CT images found that microwave ablation created larger, more uniform circular zones around ablated regions of normal porcine lungs, improving the chances that the targeted tumour and satellite tumour deposits just outside its periphery would be included in the ablated zone.
Thermal ablation is being used with increasing frequency for treating unresectable lung tumours, both as a primary treatment strategy and as an adjuvant to external radiation, wrote Christopher Brace and colleagues from the University of Wisconsin's Clinical Sciences Center in Madison, WI.
But RF ablation also comes with daunting technical deficiencies, particularly in the high-impedance path it creates in lung tissue inflated during treatment. The resulting lower energy deposition reduces the temperature to which the ablation zone can be successfully raised, increasing the chances of failed treatment - and the possibility that satellite tumour deposits just beyond the periphery will be left intact. The use of multipronged electrodes increases impedance in RF ablation, but it also increases the invasiveness of the procedure and the unpredictability of coverage.
In contrast, "microwave energy penetration is not limited by the lower electrical permittivity and conductivity of inflated lung, desiccated tissue, or charred tissue," wrote Brace and his team. "Unlike RF electrodes, microwave antennas do not require the placement of grounding pads, and multiple antennas can be operated simultaneously in close proximity without switching" (Radiology doi: 10.1148/radiol.2513081564).
Because the two techniques have not been compared, the study sought to evaluate the performance of equivalently sized radiofrequency and microwave ablation applicators in the lungs of eight pigs.
Brace, along with J Louis Hinshaw, Paul Laeseke and colleagues, performed a total of 18 ablations in vivo in the lungs of three female swine following sedation with tiletamine hydrochloride, zolazepam hydrochloride, and anaesthesia using 2% inhaled isoflurane.
RF and microwave ablation applicators were placed peripherally in normal porcine lungs by using CT fluoroscopic guidance (LightSpeed Plus, GE Healthcare, Chalfont St. Giles, UK). Applicators were used to prevent overlap of ablation zones and to avoid heat sinks (such as large vessels) that might alter the results. Three applicators of each energy type resulted in six ablations per animal.
Ablations were performed for 10 minutes by using either 125 W of microwave power or 200 W of RF power delivered with an impedance-based pulsing algorithm. CT images were acquired every minute during the procedures to monitor growth of the ablated areas.
The RF method was applied via a 17-gauge internally cooled electrode (Cool-tip, Valleylab, Boulder, CO) with 3-cm active length powered by a 200-W generator with impedance-based pulsing. The microwave ablation system consisted of a prototype 17-gauge water-cooled triaxial antenna delivering power from a 2.45-GHz generator with 125-W output (CoberMuegge, Norwalk, CT). The flow rate of the cooling water was approximately 100 mL/min in both systems.
After the experiment, the ablation zones were excised and sectioned transverse to the applicator in 5-mm increments, according to the authors. Measurements of the ablated zones included minimum and maximum diameter, cross-sectional area, length, and circularity from gross specimens and CT images, using a mixed-effects model to compare measurements.
According to the results, mean diameter of the ablated zone was 25% larger with microwave ablation, at 3.32 cm ± 0.19 (standard deviation), versus 2.70 cm ±0.23, p<0.001, with RF ablation. The mean cross-sectional area (8.25 cm2 ±0.92 versus 5.45 cm2 ±1.14, p<0.001) was 50% larger with microwave ablation than with RF ablation. With microwave ablation, the zones of ablation were also significantly more circular in cross section (mean circularity, 0.90 ±0.06 versus 0.82 ±0.09; p<0.05).
"Ablation zones achieved with microwave ablation also grew faster than those achieved with RF ablation," they wrote. "Three of nine ablation zones achieved with microwave ablation extended into the body wall, as noted by using attenuation changes on CT images."
All of the animals tolerated the procedure without complications. One small pneumothorax was found during RF ablation, but it stabilized without intervention.
"Our results indicate that microwave ablation by using a high-power generator and cooled-power delivery system outperforms RF ablation for increased ablation zone size and circularity in normal porcine lung," Brace and colleagues wrote. "Measurement variability was also slightly lower with microwave ablation, and this finding may indicate improved repeatability with the use of microwave energy."
The most likely reason for the superior performance of microwave energy is its ability to deliver power continuously over the target volume, they wrote. In contrast, RF power delivery is limited by the intrinsically high impedance of normal lung tissue due to its high air content, a problem that worsens during treatment when charred or desiccated tissue is present.
Based on previous experience showing that microwave ablation creates higher temperatures and a larger core of desiccation compared to RF ablation, and the authors' finding that microwave ablation created a larger zone of low attenuation at CT, "we hypothesize that this zone may relate to tissue desiccation that occurs at high temperatures," the group wrote. "More study is necessary to verify this theory."
The use of normal tissue was a limitation of the study, inasmuch as the properties of lung tumours are different from those of normal parenchyma. Inflated lung tissue has a high electrical impedance for RF energy, a factor that limits the power deposition of current RF systems.
"However, normal lung tissue often completely surrounds tumours and limits RF current flow in the same way as if the electrode were immersed in parenchyma," they wrote. "Therefore, we believe that the use of a normal model for this comparative study was warranted."
High-power microwave ablation using a 17-gauge triaxial antenna appears to create ablation zones that are larger and more circular than those produced by RF ablation systems using applicators of a similar diameter, the group concluded. More research is needed to compare multiple devices in the clinical setting "for a more complete characterization of the pulmonary ablation armamentarium," they wrote.


General Thoracic Surgery

Is surgery for multiple lung metastases reasonable? A total of 328 consecutive patients with multiple-laser metastasectomies with a new 1318-nm Nd:YAG laser


Axel Rolle, MD, PhD a , * , Arpad Pereszlenyi, MD, PhD a , Rainer Koch, MD, PhD b , Mathias Richard, MD a , Barbara Baier a a Department of Thoracic and Vascular Surgery, Coswig Specialised Hospital, Center for Pneumology and Thoracic Surgery, University Medical Center, Coswig/Dresden, Germany
b Department of Informatics, Carl Gustav Carus University, Dresden, Germany.

Received for publication June 20, 2005; revisions received November 17, 2005; accepted for publication November 28, 2005.
* Address for reprints: Axel Rolle, MD, PhD, Department of Thoracic and Vascular Surgery, Coswig Specialised Hospital, Center for Pneumology and Thoracic Surgery, Affiliated to the Carl Gustav Carus University Dresden, Neucoswiger Straße 21, D-01640 Coswig/Dresden, Germany (Email: dr.rolle@fachkrankenhaus-coswig.de).


FREE TEXT




OBJECTIVE: Our objective was to define the role of a new 1318-nm Nd:YAG laser for lobe- and parenchyma-saving resection of multiple lung metastases.


PATIENTS AND METHODS: From January 1996 to December 2003, a total of 3267 nodules (10/patient) were removed from 328 patients (164 men/164 women, mean age 61 years). Criteria for eligibility were expanded to any primary tumors with no upper limit of metastases given. All parenchymal resections were performed with a new 1318-nm Nd:YAG laser whose effect on lung tissue differs significantly from that of the 1064-nm wavelength owing to a 10-fold higher absorption in water and one-third extinction in blood. In 93%, precision laser resection was achieved. The lobectomy rate was only 7%.


RESULTS: Pathologic examination revealed 2546 metastases (8/patient) and lymph node disease in 19%. Complete resections (R0) were achieved in 93% of 177 patients undergoing unilateral procedures with a mean of 3 metastases (range 1%-29%) and 75% of 151 patients having bilateral operations with a mean of 13 metastases (range 2-124). The 5-year survival after R0 was 55% for solitary nodules, 41% for all patients, 28% for 10 metastases, and 26% for 20 or more metastases resected. Outcome was significantly poorer after incomplete resection (7%). No 30-day mortality was observed. Major postoperative complications included prolonged air leaks (n = 2), intrapleural bleeding (n = 2), and late pneumothorax (n = 2); all were treated successfully with a chest tube.


CONCLUSION: This new 1318-nm Nd:YAG laser facilitates complete resection of multiple bilateral centrally located metastases and thus is lobe sparing. Resection of 20 or more metastases is reasonable because long-term survival was significantly better than that observed with incomplete resection.



Infez Med. 2010 Mar;18(1):39-42.
Differential diagnosis of lung nodules: breast cancer metastases and lung tuberculosis.

Endri M, Cartei G, Zustovich F, Serino FS, Fassina A.
Department of Medicine, Operative Unit of Medicine 2, Azienda Ospedaliera Santa Maria degli Angeli, Pordenone City Hospital, Pordenone, Italy.
Abstract

In a follow-up a 74-year-old woman with breast cancer (clinical stage T4N1M0 at onset, treatment by surgical resection and tamoxifen) presented a combination of two distinct diseases in the lung: breast cancer metastasis and tuberculosis. A CT scan showed multiple pulmonary nodular lesions and in only one lesion fine needle aspiration cytology (FNAC) diagnosed tuberculosis. After specific antibiotic therapy, isoniazide and rifampin, a CT scan highlighted disappearance of tubercular lesion. Because occurrence of tuberculosis during chemo or hormone therapy for metastatic breast cancer is rare, the present case is noteworthy. Indeed, it is worth pointing out the differential diagnosis of pulmonary nodular lesions in patients with cancer and the possible reactivation of tuberculosis even in patients without specific symptoms, without typical tubercular radiological features.

PMID: 20424525 [PubMed - indexed for MEDLINE]Free Article


http://www.wsoctv.com/health/19540065/detail.html

Treating Lung Metastases: Aerosolized Chemotherapy
When osteosarcoma metastasizes, 85 percent of the time it goes to the lungs. Chemotherapy may be given to control the growth and/or slow the spread of the cancer. But the treatment can have serious side effects, like hair loss, fatigue and an increased risk for infection. The side effects occur because the anti-cancer drugs have to travel through the body to get at the cancer site in the lungs, damaging healthy cells along the way.Researchers are now testing a new way to treat osteosarcoma lung metastases, by using inhaled chemotherapy. The treatment, delivered through an inhaler, uses GM-CSF (granulocyte macrophage colony stimulating factor), also known as LEUKINE® (sargramostim), to stimulate the production of white blood cells that fight the tumor. Pete Anderson, MD, PhD, Cancer Researcher with MD Anderson Cancer Center in Houston, says the drug is normally given as a shot under the skin. But as white blood cells numbers increase, patients can experience a significant amount of aches and bone pain. When the treatment is given in an inhaled form, the drug goes directly into the airways and only the lung cells are affected. Thus, patients don’t experience the painful side effects.The inhaled chemotherapy is combined with another treatment, an experimental drug called mifamurtide, or L-MTP-PE. This medication binds to white blood cells and boosts their activity. Although given intravenously, it readily travels to the lungs where it, hopefully, strengthens the ability of the white blood cells to fight the tumor. Anderson says MTP-PE can cause high fever and chills, so patients are usually pretreated with medications, like ibuprofen or acetaminophen, to prevent the side effects.


Science fiction? Aerosol delivery of an engineered virus halts lung cancer progression in mice


July 4, 11:29 AM


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Nasal sprays containing special viruses may revolutionize the field of pharmacology to correct a multitude of devastating genetic and sporadic human diseases including lung cancer. Lung cancer in conjunction with liver and pancreatic cancer are aggressive and common manifestations of this disease worldwide. Lung cancer tops the list with over 1.3 million deaths worldwide. Currently, the prognosis for lung cancer is extremely poor and multiple options for treatments include surgical removal of lung tumors, chemotherapy and radiation. Nowadays, scientists are relentlessly working to make gene therapy delivery to the lungs a viable alternative in order to correct a variety of pulmonary dysfunctions and illnesses which include cystic fibrosis, pulmonary fibrosis and lung cancer.
Different approaches for pulmonary gene delivery include intravenous injection, nasal or intratracheal instillation. On the other hand, aerosolized or intranasal gene delivery is a very attractive approach for treating lung cancer as it is a non-invasive, fast and an efficient delivery method with high a patient compliance rate.
So what are the current technologies that have been developed to make gene delivery possible to lungs in lung cancer patients?
Nowadays, biomedically engineered viruses are being used in certain academic and

Cryoelectron microscopy image of a
a lentivirus particle. Courtesy of the University
of Iowa Lentiviral Core Facility.

clinical institutions in small scale or large scale quantities to combat a variety of genetic diseases which include cystic fibrosis and hemophilia. Many classes of viruses have been used in the past by scientists to infect a variety of organs and tissues including adenoviruses, adeno-associated viruses, and retroviruses such as lentiviruses. Lentiviruses are the most promising for gene delivery therapies since this type of virus not only infects dividing cells but also infect non-dividing cells such as neurons. On the plus side, lentiviruses allow the long-term stable integration of their genes into the genome of target cells making it possible for researchers to correct congenital deficiencies in patients by using this technology. For instance, lentiviruses carrying a copy of the cystic fibrosis transmembrane receptor have successfully being used in mouse model of cystic fibrosis to correct this disease.

Lentiviruses is a genus of the Retroviridae family of whose members include the human immunodeficiency virus (AIDS virus), feline immunodeficiency virus (FIV), the causative agent of AIDS in cats, and the simian immunodeficiency virus (SIV), the causative virus of AIDS in chimps and monkeys. These viruses are used in small quantities to infect different mouse models of disease to test different hypothesis or used in large scale quantifies for clinical applications. Of course, there is the concern that these viruses may expose the researcher or patients to the risk of developing AIDS. However, academic and federal regulations obligate scientists to take necessary safety precautions and commercially lentiviruses are modified to make them non-pathogenic. The genomes of these viruses are modified to make them replication deficient and to only induce a single round of infection. For instance, modifications of lentiviruses include deletions of accessory genes (gag, env and pol) or the genome is cut into pieces and re-packaged in more than one vector. Thus in the inconvenient event of an accidental breach in the laboratory, these lentiviruses will not survive outside the laboratory and are replication deficient. To increase their infectivity to allow researchers to infect a whole variety of cell lines, the the vesicular stomatitis virus glycoprotein (VSVG) has been added to lentiviruses to allow them to infect but a whole range of tissues including brain.
One ground-breaking study have shown the validity and practical application of lentiviruses to correct lung cancer in mice.
In the June 15 edition of the American Journal of Respiratory and Critical Care Medicine, South Korean scientists have engineered a novel intranasal delivery of special viral particles that express a tumor suppressor gene to blunt cancer progression in mice. Tumors form due to an accumulation of mutations in several genes in the cell over time which aberrantly tip the balance of many signaling pathways in cells which lead to the slow progression of neoplasms (adenomas) into a malignant tumor, and ultimately form metastases. Dr. Cho and colleagues targeted the Akt (a protein kinase) signaling pathway. Akt is a master regulator of cell survival and cell proliferation and a persistent increase in the Akt signaling can lead to a transformation of normal cells into cancer cells in vitro and in vivo. In further support of this observation, a plethora of gene expression and proteomics profiling studies in lung and many other types of cancer have demonstrated that the Akt signaling pathway is up-regulated. Moreover, the Akt gene is amplified in many cancer cells just like the epidermal growth factor receptor is overexpressed in breast cancer. Relevant to lung cancer, it has been found that 90 percent of non-small cell lung carcinomas were associated with an aberrant activation of the Akt signaling pathway. Dr. Cho chose a commercial lentiviral vector for the same reasons that these type of viruses infect non-dividing cells and promote persistent and table genetic changes in cells. Dr. Cho and colleagues further modified the lentiviral vector to include a negative regulator of Akt signaling, carboxyl-terminal modulator protein (CTMP). This bioengineered CTMP lentiviral vector was repackaged with specific viral components and amplified by infecting a human renal cell line (ie., NIH 293 cells). The supernatant containing the virus was collected from the infected cells, concentrated, lyophilized, vaporized and contained in aerosol sprays.
The scientists then wanted to determine whether intranasal delivery of the CTMP lentivirus is able to suppress lung cancer progression in mice containing lung tumors. Thus by generating this lentivirus, Dr. Cho postulated that the progression of lung cancer may be halted by inhibiting the Akt signaling pathway in cancer cells by overexpressing CTMP in the lung.
Indeed, their results showed just that. Long-term repeated intranasal delivery of CTMP containing lentiviruses particles (twice a week for one month) effectively reduced tumor progression in the lungs at different stages of development in a mouse model of lung cancer (K-rasLA1 mice). Histopathological analyses showed a significant reduction in the number and size of lung tumors and led to a near complete absence of bronchoalveolar tumors. This is a very important piece of data because it shows that the progression of cancer is halted at the benign state (adenoma) and does not develop in the bronchioles.
So how does CTMP halt cancer progression? Using biochemical analysis to analyze the expression levels of certain proteins, scientist found that overexpression of CTMP shut down not only Akt signaling but also protein synthesis, proliferation, angiogenesis and cell cycle progression of lung cancer cells while normal cells were not affected. Not only was lung cancer progression halted in 9-week old mice but the authors of the study found that cancer cells died from apoptosis.
Unlike chemotherapy which preferentially affects cancer cells but still has deleterious consequences to normal tissue after prolonged treatment, lentiviral mediated gene therapy “surgically” targets tumor cells while sparing normal tissue.
Dr. Cho’s concluding remarks stated that "Repeated aerosol gene delivery may provide an effective noninvasive model of gene delivery and understanding the role of CTMP in the multistage lung tumorigenesis may be essential in developing effective therapeutics for lung cancer.” These results will open the door towards patenting and openly marketing this technology in the US. More importantly, the use of many different biomedically engineered lentiviruses to treat a variety of genetic and sporadic human illnesses and can attract venture capitalism for creating start-up companies in the US. Obviously, patenting this technology will have to undergo major scrutiny in the US through the conventional, protracted and painstaking process of FDA clinical trials before aerosolized or injectable lentiviral particles may be available for gene therapy.

For more information:
To read the original press release: www.eurekalert.org/pub_releases/2009-06/ats-vvv060809.php#


http://www.examiner.com/x-11432-Pittsburgh-Medical-Technology-Examiner~y2009m7d4-Science-fiction-Aerosol-delivery-of-an-engineered-virus-halts-lung-cancer-progression-in-mice
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Old 07-01-2010, 02:18 AM   #3
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Lung mets

My grandfathers in the same stage -lung cancer spreading to the brain- so I understand what you and your friend are going through. Yes it is the end, most cancers in that stage are uncurable. Help your friend as much as you can, time is precious. God Bless
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Old 08-19-2010, 11:17 PM   #4
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Re: Lung mets

1: Cancer Res. 2008 Oct 15;68(20):8582-9. Links

Allergic pulmonary inflammation promotes the recruitment of circulating tumor cells to the lung.

Taranova AG, Maldonado D 3rd, Vachon CM, Jacobsen EA, Abdala-Valencia H, McGarry MP, Ochkur SI, Protheroe CA, Doyle A, Grant CS, Cook-Mills J, Birnbaumer L, Lee NA, Lee JJ.
Department of Biochemistry and Molecular Biology, Divisions of Pulmonary Medicine, Mayo Clinic Arizona, Scottsdale, Arizona 85259, USA.
Allergen-induced respiratory inflammation facilitates and/or elicits the extravasation of proinflammatory leukocytes by well-understood mechanisms that mediate the movement of multiple cell types. The nonspecific character of these pathways led us to hypothesize that circulating cancer cells use similar mechanisms, promoting secondary tumor formation at distal sites. To test this hypothesis, the frequency of metastasis to the lung as a function of allergic pulmonary inflammation was assessed following the i.v. injection of B16-F10 melanoma cells in mice. These studies showed that allergen-induced pulmonary inflammation resulted in a >3-fold increase in lung metastases. This increase was dependent on CD4(+) T-cell activities; however, it occurred independent of the induced eosinophilia associated with allergen provocation. Interventional strategies showed that existing therapeutic modalities for asthma, such as inhaled corticosteroids, were sufficient to block the enhanced pulmonary recruitment of cancer cells from circulation. Additional mechanistic studies further suggested that the ability of circulating cancer cells to extravasate to surrounding lung tissues was linked to the activation of the vascular endothelium via one or more Galpha(i)-coupled receptors. Interestingly, a survey of a clinical breast cancer surgical database showed that the incidence of asthma was higher among patients with lung metastases. Thus, our data show that allergic respiratory inflammation may represent a risk factor for the development of lung metastases and suggest that amelioration of the pulmonary inflammation associated with asthma will have a direct and immediate benefit to the 7% to 8% of breast cancer patients with this lung disease.
PMID: 18922934 [PubMed - indexed for MEDLINE]
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Old 08-21-2010, 02:12 PM   #5
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Re: Lung mets

Rich,

Thanks for this excellent resource on ablative techniques.

Some heavy hitters are represented here as authors, including the person who did my RFA.

Joan
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