HUMAN MOLECULES; INHALATION THERAPY FOR LUNG CANCER
Inhalation, or respiratory therapy is a discipline of medicine that dates back to ancient times. Recent technological advances with inhalation devices have led to innovative respiratory therapies that include treatments for lung cancers. The proposal herein projects a clinical trial utilizing normal human molecules that have shown a possible propensity to re-differentiate cancer cells, and to aerosolize these products in order to infuse them into the lungs of lung cancer patients. These molecules have had a research history of successful in vitro, in vivo studies, and a FDA IRB approved clinical trial. The concept herein poses to emulate recent lung cancer inhalation clinical trials that utilized the usual chemotherapeutic agents and to substitute these normal human molecules for those chemotherapeutic agents. These molecules have been shown to be non-toxic and are recognized by the body as self, because they are self.
Lung cancer is the number 1 cancer killer of American men and women. It kills more people than breast, prostate, colon, liver, kidney, and melanoma cancers, combined. Lung cancer kills more women than breast cancer and ovarian combined annually. The main types of lung cancer are non-small cell lung carcinoma, (NSCLC) 80.4%, and small cell lung carcinoma, (SCLC) 16.8 %. This distinction is important because the treatment varies; NSCLC is sometimes treated with surgery, while SCLC usually treated with chemotherapy.
The lung is a common site for metastasis from tumors in other parts of the body. The site of origin identifies these cancers. Thus a breast cancer metastasis is still considered as breast cancer.
The present day treatment for lung cancer depends on the cancer‘s specific type, how far it has spread, and the patient’s performance status. The common treatments for several decades have continued to be surgery, chemotherapy, and radiation therapy. Nonetheless, with these therapies the overall 5 year survival rate is 14% in the USA. This survival rate has been the same for over three decades.
WHY USE CELLULAR FIBRONECTIN AND EXTRACELLULAR MATRIX MOLECULES THERAPEUTICALLY
These molecules are already being used therapeutically by the human bodies, and have been used evolutionarily in all metazoan organisms for millions of years.
Cellular fibronectin, a dimeric cell-adhesive extracellular matrix glycoprotein is secreted by mesenchymal cells and assembled into insoluble matrices which have important biological functions in embryonic development as well as in tissue response to injury. This adhesive protein promotes cell proliferation and cytodifferentiation. Following tissue injury, newly expressed cellular fibronectin matrices are critical for tissue repair.
In the lung there is documented evidence that there is increase expression of cellular fibronectin in numerous pulmonary conditions. They include adult respiratory distress (ARDS), bronchiolitis obliterans organizing pneumonia (BOOP), and idiopathic pulmonary fibrosis (IPF). Therefore, lung tissues are already familiar with their own secreted cellular fibronectin at their interfaces.
Fibronectin, when added exogenously, in vitro, has shown the ability induce a variety of newly transformed, and various long-term cancer cell to revert their phenotype and morphologies to a more normal cell type. It restores its usual integrins that are missing from the cancer cell’s surface as an initial step in this ability to induce redifferentiation. Cellular fibronectin, in an in vivo SBIR breast tumor murine model study, has shown to inhibit cancer recurrence at the surgical site. This would have clinical application for lung cancer surgeries.
The specific extracellular matrix purified from lung fetal lung fibroblasts (MRC-5) may be of value in treating lung cancers, in addition to lung cellular fibronectin also purified from MRC-5. MRC-5 is a FDA approved normal fetal lung fibroblast cell culture that is used by many pharmaceutical companies for vaccine production.
DOXYCYCLINE: The non-antibiotic activity of doxycycline attenuates the detrimental activity of several metalloproteinases that are produced by cancer cells. Metalloproteinases are the enzymes that cancer cells use to invade normal tissue by dissolving structural molecules of the extracellular matrix and help malignant cells to metastasis. Doxycycline is a valuable adjunct to cancer therapy.
INHALATION DEVICES TECHNOLGY FOR THIS CONCEPT
There are a number of inhalation devices that may be able aerosolize these biological molecules without destroying their biological activities. These products are purified under sterile conditions and then lyophilized. They can be stored in a freezer for at least 2 years. They are reconstituted with sterile water shortly before use. These molecules are purified with the buffered saline so that they are physiologically ready to use after the reconstitution by the sterile water.
A simple nebulizers that would not need a fine mist, and one whose action would be sufficiently gentle as to not degrade these biological molecules would suffice.
TENTATIVE CLINICAL TRIAL
The first trials should perhaps only utilize the cellular fibronectin and the doxycyline. Patient monitoring may eventually indicate that the addition of the extracellular matrix molecules may be of benefit.
CHIFYX’S Inhalation Therapy Lung Cancer Kit Each kit will contain the products for the clinical trials once a week for three weeks.
Kit’s sterile contents:
- 3 vials of Doxycycline powder 10 mgs per vial.
- 3 vials of lyophilized fetal lung Cellular Fibronectin 5 mgs per vial.
- 3 vials of lyophilized fetal lung Extracellular Matrix Molecules 7.5 mgs per vial.
- 3 vials of sterile water 25 mls per vial
- 3 sterile 5 ml syringe
Take out of the Kit:
- 1 vial doxycycline 1 vial cellular fibronectin
- 1 vial extracellular matrix
- 1-5 ml syringe
After the patient is deemed ready for the procedure:
- Reconstitute each vial with 5 mls sterile water
- Doxycycline is infused first to start the procedure
- Wait 15 minutes
- Infuse the total amount of fetal lung cellular fibronectin
- Wait 15 minutes
Finish the protocol by infusing the total fetal lung extracellular matrix.
This protocol may be repeated once a week for 2 more weeks depending on the patient’s reaction to these procedures.