Newly discovered gene plays vital role in cancer

[PRESS RELEASE, 27 February 2009] Gene p53 protects against cancer and is usually described as the most important gene in cancer research. However, scientists at Karolinska Institutet have now shown that a previously unknown gene, Wrap53, controls the activity of p53. As the regulation mechanism is relatively unexplored, the study opens up new routes to solving the mystery of cancer.

Marianne Farnebo Photo: private

The p53 gene makes sure that cells with damaged DNA either repair themselves or commit suicide. If p53 itself is damaged, which is the case in roughly half of all cancer tumours, cells that are on their way to becoming cancerous are allowed to survive. Much cancer research revolves around the cell processes that p53 induces.

A group of researchers at Karolinska Institutet have now identified a new gene, called Wrap53, that regulates the activity of p53. The study, which is published in the journal Molecular Cell, demonstrates that Wrap53 gives rise to a molecule, called antisense RNA, the presence of which is necessary for the production of sufficient quantities of p53 protein in the event of DNA damage.

According to Marianne Farnebo, one of the scientists involved in the study, the results indicate that damage to Wrap53 can indirectly cause cancer. Wrap53 is therefore a new potential target for future cancer therapies.

"Mutations in the p53 gene contribute to about half of all cancer cases," she says. "In the remaining half, p53 is probably inactivated in other ways, such as damage to Wrap53 knocking out the production of the p53 protein."

The study is also one of the first to show how antisense RNA regulates genes in the human body. It is already a well-known fact that genes often control each other through the influence of their end products - usually proteins - on gene expression. With antisense regulation, control is effected instead through the production of mutually stabilising or destructive RNA molecules by genes with overlapping sequences, which determines whether or not the RNA molecules form proteins.

"At least 20 per cent of all genes can be regulated by antisense RNA, making it a potentially very common control mechanism," says Dr Farnebo. "But it's been difficult to show that antisense RNA really does serve important functions in the body, as we've managed to do in this study."

Publication:
Salah Mahmoudi, Sofia Henriksson, Martin Corcoran, Cristina Méndez-Vidal, Klas G. Wiman & Marianne Farnebo
Wrap53, a natural p53 antisense transcript required for p53 induction upon DNA damage

For more information, please contact:
PhD Marianne Farnebo

Work:
+46 (0)8-517 703 67
Mobile:
+46 (0)70-217 42 04

E-mail:

* Marianne.Farnebo@ki.se

* Department of Oncology-Pathology

Source

Re 636 nm spectral poperties

Absorption Spectra of Formylchlorins

The absorption spectra of the formylchlorins (in toluene at room temperature) are summarized in Table 2. Three classes are noted: zinc chlorins bearing a 10-mesityl group (ZnC-M¹⁰ series); zinc chlorins bearing a 5-p-tolyl group and a 10-mesityl group (ZnC-T⁵M¹⁰ series); and various free base chlorins (FbC series). Selected absorption spectra of the ZnC-M¹⁰ series are shown in Figure 1 (see Supporting Information for additional spectra).

Table 2 Spectral Properties of Chlorins.a

Figure 1 Absorption spectra (normalized) in toluene at room temperature of ZnC-M10 (trace a, λQy 606 nm),17ZnC-M10F13 (trace b, λQy 634 nm), ZnC-F5P10 (trace c, λQy 650 nm), and ZnC-F3M10F13 (trace d, λQy 667 nm).

The long-wavelength absorption band can now be tuned over the range of 606 – 667 nm.

Source

Comparison between sonodynamic effect with protoporphyrin IX and hematoporphyrin on sarcoma 180

Journal	Cancer Chemotherapy and Pharmacology
Publisher	Springer Berlin / Heidelberg
ISSN	0344-5704 (Print) 1432-0843 (Online)
Issue	Volume 60, Number 5 / October, 2007
Category	Original Article
DOI	10.1007/s00280-006-0413-4
Pages	671-680
Subject Collection	Biomedical and Life Sciences
SpringerLink Date	Friday, January 12, 2007

PDF (608.2 KB)HTMLFree Preview

QuanHong Liu¹ , XiaoBing Wang¹, Pan Wang¹, LiNa Xiao¹ and Qiao Hao¹

(1)	College of Life Sciences, Shaanxi Normal University, Xi’an, 710062, China

Received: 14 October 2006 Accepted: 21 December 2006 Published online: 12 January 2007

Abstract

Purpose
The comparison between sonodynamic antitumor effect with protoporphyrin IX (PPIX) and hematoporphyrin (Hp) at a concentration of 5 mg/kg on Sarcoma 180 (S180) cells was studied in vivo, and the potential cell damage mechanism was also investigated.

Methods
The sonodynamically induced anti-tumor effect of PPIX was studied in mice bearing S180 solid tumors. In order to determine the optimum timing of ultrasound exposure after administration of PPIX, the PPIX concentrations in plasma, skin, muscle and tumor were determined by the fluorescence intensity of tissue extractions with a fluorescence spectrophotometer based on the standard curve. Anti-tumor effects were estimated by measuring the tumor size and the tumor weight. Additionally, the morphological changes of S180 cells were evaluated by transmission electron microscope (TEM) observation immediately after sonodynamic therapy (SDT) treatment.

Results
A time of 24 h after the intravenous administration of PPIX was chosen as the best time for ultrasound exposure. The antitumor effect induced by PPIX mediated sonodynamic therapy (PPIX-SDT) was in a dose dependent manner when ultrasound intensity was at or above the inertial cavitation threshold (5 W/cm²). A significant tumor growth delay was observed both in PPIX mediated sonodynamic therapy and in Hp mediated sonodynamic therapy treatments (Hp-SDT), and the tumor weight inhibition ratios after the synergistic treatments were 42.82 ± 0.03 and 35.22 ± 0.03%, respectively, this difference was significant at P <>2) showed a slight tumor growth inhibitory effect compared with the control group, and PPIX or Hp alone showed almost no significant effect. Furthermore, TEM observation indicated cell damage was more serious in PPIX-SDT treatment group than in Hp-SDT treatment group. After sonication, the cell ultra-structure such as cell membrane destruction, mitochondria swelling, chromatin condensation might be important factors that inhibited the tumor growth and even induced cell death.

Conclusions
The comparative results suggested that PPIX as a sonosensitizer might have more potential cytotoxicity than Hp when irradiated with ultrasound, and the ultra-structural changes may account for cell destruction induced by sonodynamic therapy in our experiment mode.

Keywords Sonodynamic therapy - Anti-tumor effect - Protoporphyrin IX - Hematoporphyrin - Sarcoma 180

---

QuanHong Liu Email: lshaof@snnu.edu.cn Source

Combination sonodynamic therapy with immunoadjuvant may be a promising new modality for cancer treatment

doi:10.1016/j.mehy.2008.10.024

Copyright © 2008 Elsevier Ltd All rights reserved.

Combination sonodynamic therapy with immunoadjuvant may be a promising new modality for cancer treatment

References and further reading may be available for this article. To view references and further reading you must purchase this article.

Xiaopeng Ma^{a, 1}, Huixuan Pan^{b, 1} and Jilin Yi^{a, , ,}

^aDepartment of Breast and Thyroid Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

^bDepartment of Nephrology, First Affiliated Hospital, School of Medicine, Yangtze University, Jingzhou 434000, China

Received 23 September 2008;

accepted 2 October 2008.

Available online 6 January 2009.

Summary

Sonodynamic therapy (SDT) is a new cancer therapy basing on photodynamic therapy (PDT). Some chemicals produce free radicals on irradiation with laser (photosensitizers) or ultrasound (sonosensitizers). These active molecules destroy biological tissues, thus producing therapeutic effects. Although PDT has been adopted in clinical cancer therapy especially for superficial cancers, this modality is under continued investigation for improved efficacy and expanded use. For example, PDT-generated tumor cell lysates are effective cancer vaccines; treatment of PDT in conjunction with immunoadjuvant, called “PDT-immunoadjuvant therapy” (PIT), “photoimmunotherapy” or “laser immunotherapy”, is considered to be a promising therapeutic interventions for the treatment of cancers. Ultrasound, especially focused ultrasound, can penetrate deeply into tissues and can be focused into a small region of a tumor to activate the cytotoxicity of sonosensitizers. This is a unique advantage in the non-invasive treatment of nonsuperficial tumors when compared to laser light used for PDT. For the similar mechanism of PDT and SDT, we hypothesize that SDT may be exploited for the generation of effective therapeutic cancer vaccines like PDT; and combination SDT with Immunoadjuvant may be a promising systemic treatment modality, not only for superficial cancers but also for deep-seated tumors, which would surpass PIT.

Article Outline

Introduction

The similar principle, process, drugs and mechanism of PDT and SDT

PDT-generated tumor cell lysates (in vitro) are effective cancer vaccines

‘‘PDT-immunoadjuvant therapy” forms an in situ autovaccine

The unique advantage of ultrasound

Hypotheses

Future perspectives

Acknowledgements

References

Corresponding author. Tel.: +86 27 83663818; fax: +86 27 83662851.
¹ These authors contributed equally to this study.

Source

Photodynamic and Sonodynamic Therapy, Experiences with a Novel Approach

JNK/Ak
Masters/JNK Papers/ Photodynamic and Sonodynamic Therapy – A Novel Approach
October 2007

Photodynamic and Sonodynamic Therapy, Experiences with a Novel Approach.

Introduction

I have been asked to write a paper on our experiences and methods and also results, in our use of a novel approach to Photodynamic Therapy. This is something we have been developing for several years, together with two other clinics, Dr X Wang, Chief of Oncology Department, Friendship Hospital, Guangzhou, China and also the Opal Clinic, Melbourne, Australia under the direction of Dr Douglas Mitchell. The reason why all three clinics developed this approach is that we are all faced with late stage cancer patients who have been through all the conventional treatment modalities, and are practically all metastatic cancers. We therefore have an interest in a safe approach to tumour cell destruction, however in all of these patients the approach is fundamentally palliative. Our results have been encouraging leading to relevant conclusions outlined in the last section of this paper. Over the past three years our clinic (The Dove Clinic for Integrated Medicine) has treated over 80 patients, the Opal Clinic has treated slightly less, and Dr Wang in Guangzhou has treated more than this number. This paper is not a formal clinical trial, it is a preliminary report. I therefore thought it best to discuss five cases fairly typical of the kind of cases on which we use this palliative approach. The use of our novel approach centres around the development of a specific sensitizer (Sonalux 1) this is a highly purified mixture of several chlorins, each with a different side chain. This agent has been shown to break down at 636 nanometres and also to be sensitive to ultrasound.
.........

Source

Thomas J. Lewis, PhD

17^th Annual World Congress on Anti-Aging Medicine

23 - 25 April 2009 Orlando, FL, USA

16^th Annual World Congress on Anti-Aging Medicine

11 - 14 December 2008 Las Vegas, Nevada, USA

Thomas J. Lewis, PhD

Dr. Thomas J. Lewis holds a Ph.D. in Inorganic and Physical Chemistry from MIT (1984). His research career focused mainly on kinetics and electron transfer properties of metal centered macrocycles. He has consulted in toxicology to much of big Pharma. Recently he developed several new sonodynamic therapeutic agents for cancer treatment.

Source 1

Source 2

Primary clinical use of sonodynamic therapy (SDT) for advanced breast cancer

Sub-category: New Systemic Agents – Cytotoxics

Category: Treatment Meeting:

2008 Breast Cancer Symposium


Abstract No: 194

Author(s): T. J. Lewis, X. Wang

Abstract:

Background: Sonodynamic therapy (SDT), the synergistic effect of drugs and ultrasound, is promising for cancer treatment. A new sonosensitizing agent has been developed that is derived from chlorophyll, is sensitive to red light, and is extremely sensitive to ultrasound. This agent is specifically absorbed in tumor cells and produces cytotoxic moities upon interaction with 'diagnostic' ultrasound. Animal studies show that SDT inhibits growth of mouse S-180 sarcoma. Here we report clinical data for SDT for advanced breast cancer on 20 patients. Patients were considered late stage with metastasized carcinomas. Prior to SDT treatment, all patients had undergone convention therapies but received no benefit. Methods: All patients had pathologically proven breast carcinomas. The SDT agent was given to patients sublingually with a total dose of 30 to 60mg. After 24h, ultrasound was used to irradiate the general area of the tumors. Sound application was repeated one and two weeks later. Results: ~90% of patients treated experienced a positive response to SDT therapy. 35% experienced "excellent" responses with marked tumor elimination and alleviation of symptoms that was tracked for >1 year, eg. "Case 1." 30% experienced "good" responses also with tumor diminution and symptom relief, eg. "Case 2." Case 1 had left breast carcinoma with multi-organ metastases including auxiliary lymph nodes, bones, liver and abdomen lymph nodes. After 2 treatments PET/CT scan showed good PR. The latest PET/CT taken 28 months after the treatment showed no signs of tumor in any cavity of the body. Case 2 had breast carcinoma which spread broadly. The patient had surgery, chemo, RT, hormone, trastuzumab, zoledronic acid, etc, but all failed. The tumor kept growing until the patient had high-level paraplegia, breath failure, and heart failure. After 3 SDT treatments the patient's symptom improved significantly. Windpipe spile, gastric and urine catheter were all taken off. PET/CT scan showed a partial response. The patient died 7 months later. Conclusions: Primary clinical data shows that SDT is well tolerated and has a significant therapeutic effect for patients with advanced breast cancer. Terminally ill patient can be treated safely and effectively. Sonodynamic therapy has significant merit for further investigation.

Source

194 - SonneMed, LLC
Source

Cancer treatment innovator dies

Kanzius developed radio-based device to treat disease

By MCKENZIE CASSIDY, mcassidy@breezenewspapers.com

POSTED: February 21, 2009
Part-time Sanibel resident John Kanzius, a retired radio engineer and innovator of a groundbreaking radio-based device designed to cure cancer, died Wednesday from complications related to his own cancer treatment.

Email: "Cancer treatment innovator dies"
*To:		<--TO Email REQUIRED!
*From:		<--FROM Email REQUIRED!

Kanzius, 64, was a patient at Health Park Medical Center receiving care for a bout of pneumonia he contracted after two recent rounds of chemotherapy to combat b-cell Leukemia. He is survived by his wife, Marianne; two daughters, Sherry Kanzius and Toni Palmer; and two grandchildren.

Kanzius made national headlines after designing the device capable of transmitting radio waves to essentially burn out cancerous cells. Last year he was interviewed on 60 Minutes and his unique innovation has been featured on countless news programs.

Scientists were initially shocked when Kanzius, without any formal medical degree or training, showcased the device he designed in his free time. His story began in 2003 after several painful rounds of chemotherapy when - according to an interview with the Los Angeles Times - Kanzius awoke at 2 a.m. with the idea to create a device to burn the cancer out of his body.

Since the 1960s Kanzius had worked as a broadcast engineer and later a manager in a number of radio stations across the United States.

It took several months for him to use spare wires, boxes, antennas and even his wife's pie pans to assemble the device, which he later presented to Dr. Steven Curley from M.D. Anderson Cancer Center in Houston, Texas. Richard Smalley, a Nobel Prize winning specialist in nanoscience, also assisted with perfecting the nanotubes used in the treatment before his death from cancer in 2005.

Because his residence was on Sanibel after retiring from Eerie, Pa., Kanzius approached officials from Lee Memorial Health System to include them in human trials.

Sharon MacDonald, vice president of Oncology at Lee Memorial Health System, kept regular correspondence with Kanzius up until the week he passed away. She first met Kanzius in 2007 when he approached her and LMHS President Jim Nathan about including Lee County hospitals in the research behind the cure for cancer.

"I talked to him last week and we talked about the trial and his treatment and family," said MacDonald. "Beside having a great intellect he was also well loved by his family and the community."

The local health system has been handpicked to host human trials for the device following approval by the U.S. Food and Drug Administration.

Currently, researchers are in the final stages of animal testing.

"We were good colleagues and I had great respect for him and his family," said MacDonald.

Researchers agree that if perfected the device could serve as an alternative to invasive cancer treatment.

In the work behind the Kanzius Radio Frequency Generator, Curley's research team was capable of killing cancer cells in rabbits within 120 seconds. During the experiment carbon nanotubes, or hollow cylinders made of pure carbon, were placed in a rabbit's cancerous liver and heated with radio waves.

In a statement published on the John Kanzius Research Foundation, Curley said he would continue whatever is necessary to perfect the technology and find a cure.

"John's legacy must and will live on. I will continue this important research work with renewed vigor and focus because I despise this disease that has stolen another brilliant individual from us," said Curley.

During a presentation of the device last year Curley said his team was concerned about some tissue around the nanotube sustaining heat damage during the process. Researchers have also been looking into using gold nanoparticles and a study published by the Journal of Nanobiotechnology in 2008 showed promising results.

"Our next step is to look at ways to more precisely target the nanotubes so they attach to, and are taken up by, cancer cells while avoiding normal tissue," said Curley at the end of 2007.

The John Kanzius Cancer Research Foundation continues to accept donations for research but officials are disappointed that he will never be able to see the device reach fruition.

"We will not stop until John's vision becomes reality," said Maryann Yochim, president of the Kanzius Cancer Research Foundation. "Our only regret at this point is that John will not be here to see the first cancer patient cured with his technology. But, we believe strongly that this will happen. It's only a matter of time."

The Dusckas-Martin Funeral Home in Millcreek, Penn. will handle Kanzius' funeral arrangements this weekend. The foundation Web site is www.kanziuscancerresearch.com.

Source

Opal Clinic closedown

Opal Clinic closedown

Opal Clinic closed its doors in May 2008, and is currently only treating existing patients. The problem was not with the treatment. Since closedown, the two major Opal therapies, SPDT ( described on this web site) and Enzyme Therapy are both progressing rapidly. The enzyme therapy is in the early stages of commercial development, and it continues to very significantly extend peoples lives. Our Chinese colleagues continue to develop SPDT, and this also is significantly extending people’s lives.
A major reasons for closing were that:

1. our Chinese colleagues were doing a better job;
2. we needed to spend about $250,000 to keep our equipment up to date; and
3. our Chinese colleagues have access to other useful therapies which are not available (or hard to get) in Australia

The general approach to metastatic cancer is to de-bulk or shrink tumours until they get to the size where SPDT is most effective. Our Chinese colleagues use some of the following to do this:

1. Local chemotherapy. Drugs injected directly into tumours (safer and more effective than when given to the whole body).
2. High intensity focussed ultra sound (HIFU). I believe that this is only used in Australia to treat prostate problems, with very few hospitals having the equipment. The Chinese use HIFU to treat many tumours, and Dr Wang in Guangzhou has recently improved the technology for this therapy.
3. Radioseeds inserted directly into tumours (safer than radiation from outside the body). This is done to a limited extent in Australia, but not nearly as much as our Chinese colleagues. Australia may lack the skilled surgeons to do this.
4. Hyperthermia, to safely attack large tumours which cannot be surgically removed. Widely used in Germany and China, but it does not appear to be available in Australia.

The net result is that most Australians will have to wait for regulatory approval for Opal therapies to be available in Australia and funded by insurers. We expect them to become available for one cancer type in about 2015, with others added later.
If you are interested in getting access to these treatments (outside Australia), please click here . Include your telephone number, and give a brief description of your health status, and we will direct you to the appropriate practitioners.

Doug Mitchell Ph.D
Chairman, Opal Clinic.

Source

Mechanism of Porphyrin-Induced Sonodynamic Effect: Possible Role of Hyperthermia

Radiation Research

Published by: Radiation Research SocietyRadiation Research 165(3):299-306. 2006

doi: 10.1667/RR3510.1

Mechanism of Porphyrin-Induced Sonodynamic Effect: Possible Role of Hyperthermia

Manabu Kinoshita¹ and Kullervo Hynynen

Department of Radiology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts 02115

¹Corresponding author: Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115; mkinosit@bwh.harvard.edu

Abstract

Kinoshita, M. and Hynynen, K. Mechanism of Porphyrin-Induced Sonodynamic Effect: Possible Role of Hyperthermia. Radiat. Res. 165, 299–306 (2006).

The biological effects of ultrasound have been investigated vigorously for various applications including the thermal coagulation of tissues, the opening of tight junctions, and localized gene or drug introduction. The synergistic cell killing effect of ultrasound and porphyrin derivatives, the so-called sonodynamic effect, holds promise for cancer treatment. Although several models to explain the sonodynamic effect have been proposed, its exact mechanism, especially in vivo, remains unknown. We examined the effect of a porphyrin derivative, protoporphyrin IX, on ultrasound-induced killing of HeLa cells. In some experiments, the intracellular protoporphyrin IX concentration was increased by 5-aminolevulinic acid treatment of the cells. Although extracellular protoporphyrin IX showed an enhanced cell killing effect by microbubble-enhanced ultrasound, intracellular protoporphyrin IX did not. On the other hand, intracellular protoporphyrin IX enhanced the cell killing effect of hyperthermia, which can be produced by ultrasound exposure, in a moderately acidic environment (pH 6.6). Because porphyrin derivatives are generally imported into the intracellular component in vivo, our results suggest that hyperthermia caused by ultrasound may play an important role in the sonodynamic effect induced by porphyrin derivatives.

Received: March 29, 2005; Accepted: June 10, 2005

Source

Sonodynamic Antitumor Effect of Protoporphyrin IX

Vol. 53, No. 6, 2007 View or print article as PDF (277 KB) Experimental Chemotherapy Sonodynamic Antitumor Effect of Protoporphyrin IX Disodium Salt on S180 Solid Tumor Quanhong Liu, Xiaobing Wang, Pan Wang, Lina Xiao College of Life Science, Shaanxi Normal University, Xi'an, China Address of Corresponding Author Chemotherapy 2007;53:429-436 (DOI: 10.1159/000110008) Key Words Sonodynamic therapy Antitumor effect Protoporphyrin IX Sarcoma 180 solid tumor Abstract Background: The sonodynamically induced antitumor effect of protoporphyrin IX (PPIX) disodium salt was studied in mice bearing sarcoma 180 solid tumors. Methods: In order to determine the optimum timing of ultrasound exposure after administration of PPIX, the PPIX concentrations in plasma, skin, muscle and tumor were estimated by measuring the fluorescence intensity of tissue extractions with a fluorescence photometer based on the standard curve. Antitumor effects were estimated by measuring tumor size and calculating the average survival time of tumor-bearing mice after sonodynamic therapy; additionally, the morphological changes of sarcoma 180 cells were evaluated by transmission electron microscope observation in vivo. Results: Our experiments suggested a time of 24 h after the administration of PPIX to be best for ultrasound exposure. At an ultrasound intensity 5 W/cm2 and a PPIX dose 5 mg/kg, a significant synergistic effect of ultrasound combined with PPIX was observed, reducing tumor volume and increasing average animal survival time; this synergistic effect was obviously stronger than ultrasound treatment alone, while PPIX alone showed no significant effect. Transmission electron microscope observation indicated that changes in cell ultrastructure, such as cell membrane destruction, mitochondria swelling and chromatin condensation, were important factors that inhibited tumor growth and even induced cell death. Conclusion: The results implied that the antitumor effect of ultrasound could be enhanced in the presence of PPIX which might be involved in a sonochemical mechanism. Copyright © 2007 S. Karger AG, Basel Source

Primary clinical use of sonodynamic therapy (SDT) for advanced breast cancer

Journal of Clinical Oncology, 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 26, No 15S (May 20 Supplement), 2008: 12029
© 2008 American Society of Clinical Oncology

Abstract

X. J. Wang, D. Mitchell and T. J. Lewis

Liu Hua Qiao Hospital, Boston, MA; Opal Clinic, Victoria, Australia; SonneMed, LLC, Boston, MA

12029

Background: There are increasing data showing that sonodynamic therapy (SDT), which refers to a synergistic effect of drugs and ultrasound, is a promising new modality for cancer treatment. Recently a new sonosensitizing agent has been developed by SonneMed, LLC. It is extremely sensitive to ultrasound. As with photodynamic sensitizers, it is specifically absorbed into tumor cells and produces singlet oxygen upon interaction with the right frequency and intensity of ultrasound. The singlet oxygen is able to create cellular necrosis. Our animal studies showed that SDT with SF1 inhibits growth of mouse S-180 sarcoma. Here we report initial clinical data using SDT with SF1 for advanced breast cancer. Methods: Three patients with metastasized pathologically proven breast carcinoma were studied. Their carcinoma failed to respond to conventional therapy and spread to the whole body. The SDT agent was provided through lingual absorption. After 24h, light and ultrasound was applied, irradiating the tumour area for 20 minutes daily for 4 days and repeated every two weeks. Results: Case 1 had breast carcinoma which spread to the whole body. She had surgery, chemo, RT, hormone, Herceptin, Zometa etc, but all failed. The tumor kept growing until she multiple acute symptoms. After 3 SDT treatments her symptom improved significantly and windpipe spile, gastric and urine catheter were all taken off. PET/CT scans showed a positive partial result (PR). Case 2 had left breast carcinoma with multi-organ metastases. After 2 treatments PET/CT scan showed very positive PR. PET/CT taken 28 months after treatment showed no signs of tumor in any cavity of the body. Case 3 had left breast carcinoma. All conventional treatments failed. Her carcinoma metastases broadly and her marrow function was very poor. After 2 cycle treatments PET/CT scan showed PR. Conclusions: Primary clinical data shows that SDT with SF1 is well tolerated and has a significant therapeutic effect for some patients with advanced breast cancer. Even a terminally ill patient can be treated safely and effectively. Sonodynamic therapy with SF1 has significant merit for further investigation.

No significant financial relationships to disclose.

Source

XIAOHUAI WANG - acoustodynamic therapy

Application of porphyrin class in preparation of sound motivation therapy medicine and sound motivation therapy

Bibliographic data

Description

Claims

Mosaics

Original document

INPADOC legal status

	Publication number: CN101156848 (A) Publication date: 2008-04-09 Inventor(s): XIAOHUAI WANG [CN]; JIANGAN SU [CN]; QING LI [CN]; GUANGLIAN ZHAO [CN]; YIFAN LUO [CN]; BO YU [CN] Applicant(s): BO YU [CN] Classification: - international: A61K31/409; A61P35/00; A61K31/409; A61P35/00 - European: Application number: CN20071164244 20070930 Priority number(s): CN20071164244 20070930 View INPADOC patent family View list of citing documents Report a data error here Abstract of CN 101156848 (A) The invention provides the application of porphyrin chemical compound which is in one of the right formulas in preparing a drug of acoustodynamic therapy and the acoustodynamic therapy. The acoustodynamic therapy includes the steps that the porphyrin chemical compound is applied to a patient, and then acoustic wave acts on the patient, wherein, the meaning of each symbol is as stated in the instruction. Data supplied from the esp@cenet database — Worldwide

Source

In this Chinese patent - 'chlorlin' is mentioned and this is Wikipedia's description for 'chlorin' - no 2nd "l" (which may be correct, at least it involves PDT):

Chlorin:
From Wikipedia, the free encyclopedia

Jump to: navigation, search

For the chemical element in the halogen group see chlorine.

Chlorin
Identifiers
PubChem	65106
SMILES	[show] C1CC2=NC1=CC3=CC=C(N3)C=C4C=CC(=N4)C=C5C=CC(=C2)N5
Properties
Molecular formula	C20H16N4
Molar mass	312.36784
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox references

In organic chemistry, a chlorin is a large heterocyclic aromatic ring consisting, at the core, of three pyrroles and one pyrroline coupled through four methine linkages. Unlike a porphyrin, a chlorin is therefore largely aromatic but not aromatic through the entire circumference of the ring.

Magnesium-containing chlorins are called chlorophylls, and are the central photosensitive pigment in chloroplasts. A related compound, with two reduced pyrroles, is called a bacteriochlorin.

Because of their photosensitivity, chlorins are in active use as photosensitizing agents in experimental Photodynamic Therapy.

See also: Sonodynamic therapy (mentions SonneMed)

SonneMed - Sonodynamic Therapy

The Tumoricidal Effect of Sonodynamic Therapy (SDT) on S-180

Integrative Cancer Therapies, Vol. 7, No. 2, 96-102 (2008)
DOI: 10.1177/1534735408319065

Sarcoma in Mice
Xiaohuai Wang, MD

Department of Oncology, Liu Hua Qiao Hospital, Guangzhou, P. R. China, tlewis@sonnemed.com

Thomas J. Lewis, PhD

SonneMed LLC, Boston, Massachusetts

Doug Mitchell, PhD

There are increasing data showing that sonodynamic therapy (SDT), which refers to a synergistic effect of drugs and ultrasound, is a promising new modality for cancer treatment. However, few clinical data on SDT have been published. One reason is the lack of suitable drugs for clinical SDT use. Recently a new sonosensitizing agent has been developed by SonneMed, LLC, referred to as SF1. In this study the effect of SDT with SF1 on S-180 sarcoma in mice was examined. The tumor bearing mice were allocated to the following groups: (1) sham-treatment (control, C); (2) ultrasound treatment (only ultrasound treatment, 1.2 mW/cm2 , without SF1, U); (3) SF1 treatment (SF1 20 mg/kg intraperitoneal [ip] without ultrasound treatment, S); and (4) SF1 + ultrasound treatment (SU). Following treatment, tumor volume was monitored. Tumor growth inhibition was seen only in group SU, and with increasing ultrasound intensity, the inhibitory effect was enhanced. Tumor growth inhibition was also visible even when covered by a barrier of bone. Pathological slices showed coagulated necrosis or metamorphic tissue with inflammatory reaction in the tumor taken from 2 to 36 hours after SDT. These data revealed that SDT with SF1 did inhibit growth of mouse S-180 sarcoma and the inhibitory effect was sound intensity dependent. SDT also induced some inflammation while it destroyed the tumor, indicative of a "vaccine" effect. SF1 shows great promise for clinical use in the future.

Key Words: photodynamic therapy • sonodynamic therapy • cancer • cancer therapy • tumor necrosis • tumoricidal • poryphrins • SonneMed • mouse S-180 sarcoma • anticancer

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(WO/2009/023778) OPTICAL RECTIFICATION DEVICE AND METHOD OF MAKING SAME

• Biblio. Data
• Description
• Claims
• National Phase
• Notices
• Documents

Latest bibliographic data on file with the International Bureau Permanent Link Bookmark this page
Pub. No.: WO/2009/023778 International Application No.: PCT/US2008/073175 Publication Date: 19.02.2009 International Filing Date: 14.08.2008
IPC:	H01G 9/20 (2006.01)
Applicants:	WILLIAM MARSH RICE UNIVERSITY [US/US]; 6100 Main Street, Houston, TX 77005 (US) (All Except US). SCHMIDT, Howard, K. [US/US]; (US) (US Only). DUQUE, Juan [US/US]; (US) (US Only).
Inventors:	SCHMIDT, Howard, K.; (US). DUQUE, Juan; (US).
Agent:	SHADDOX, Robert, C.; Winstead Pc, P.o. Box 50784, Dallas, TX 75201 (US).
Priority Data:	60/955,816 14.08.2007 US

Title:	OPTICAL RECTIFICATION DEVICE AND METHOD OF MAKING SAME (Click pic to enlarge)
Abstract:	A general approach is provided for producing devices that absorb optical photons (visible to near IR) and performs charge separation with a useful voltage between holes and electrons. These holes and electrons may be collected in electrodes for performing useful work outside the device. The described technology is generally based upon rectification of plasmons (collective electric excitations) generated by absorbing light with tuned metallic antennas. According to some embodiments, the present invention provides a spatial array of nanoscale conductors forming an optical rectenna that responds to an incident light source and generates a current offset that may be rectified by a rectification-inducing material. The present inventors foresee an extensive use of these optical rectennas as photovoltaic devices, as well as a wide interest in diverse fundamental research and applied technologies.
Designated States:	AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. African Regional Intellectual Property Org. (ARIPO) (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW) Eurasian Patent Organization (EAPO) (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM) European Patent Office (EPO) (AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MT, NL, NO, PL, PT, RO, SE, SI, SK, TR) African Intellectual Property Organization (OAPI) (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG).

Publication Language:	English (EN)
Filing Language:	English (EN)

WHAT IS CLAIMED IS:

1. An optical rectification device, comprising:

a plurality of optically responsive members, each optically responsive member comprising:

an optical antenna; and

a diode comprising a layer disposed over the nanostructure, the layer comprising a rectification-inducing material.

Source

Coaxial MnO2/Carbon Nanotube Array Electrodes for High-Performance Lithium Batteries

Letter

• Abstract
• Full Text HTML
• Hi-Res PDF[969 KB]
• PDF w/ Links[233 KB]

• Supporting Info

Arava Leela Mohana Reddy^†, Manikoth M. Shaijumon^†, Sanketh R. Gowda^‡ and Pulickel M. Ajayan*^†

Department of Mechanical Engineering & Materials Science, and Department of Chemical & Biomolecular Engineering, Rice University, 6100 Main Street, Houston, Texas 77005

Nano Lett., Article ASAP

DOI: 10.1021/nl803081j

Publication Date (Web): February 2, 2009

Copyright © 2009 American Chemical Society

†

Department of Mechanical Engineering & Materials Science.

,

‡

Department of Chemical & Biomolecular Engineering.

,

* To whom correspondence should be addressed, ajayan@rice.edu.

Abstract

Coaxial manganese oxide/carbon nanotube (CNT) arrays deposited inside porous alumina templates were used as cathodes in a lithium battery. Excellent cyclic stability and capacity of MnO₂/CNT coaxial nanotube electrodes resulted from the hybrid nature of the electrodes with improved electronic conductivity and dual mechanism of lithium storage. The reversible capacity of the battery was increased by an order compared to template grown MnO₂ nanotubes, making them suitable electrodes for advanced Li ion batteries.

View: Full Text HTML | Hi-Res PDF | PDF w/ Links

Source

Targeted Immune Cells Shrink Tumors In Mice

ScienceDaily (Feb. 14, 2009) — Researchers have generated altered immune cells that are able to shrink, and in some cases eradicate, large tumors in mice. The immune cells target mesothelin, a protein that is highly expressed, or translated in large amounts from the mesothelin gene, on the surface of several types of cancer cells. The approach, developed by researchers at the University of Pennsylvania School of Medicine and the National Cancer Institute (NCI), shows promise in the development of immunotherapies for certain tumors.

Expression of mesothelin is normally limited to the cells that make up the protective lining (mesothelium) of the body’s cavities and internal organs. However, the protein is abundantly expressed by nearly all pancreatic cancers and mesotheliomas and by many ovarian and non-small-cell lung cancers. Although the biological function of mesothelin is not known for certain, it is thought to play a role in the growth and metastatic spread of the cancers that express it.

“Since tumor cells are derived from the body’s normal cells, the immune system often does not recognize tumor molecules as dangerous or foreign and does not mount a strong attack against them,” said Ira Pastan, M.D., chief of the Laboratory of Molecular Biology in NCI’s Center for Cancer Research, a study collaborator. Moreover, even though it is possible to genetically engineer immune system cells to recognize molecules on tumor cells, most of the molecules found on tumor cells are also found on normal cells. But, Pastan notes, “Mesothelin is a promising candidate for generating tumor-targeting T cells, given its limited expression in normal tissues and high expression in several cancers.”

Previous laboratory research has shown that certain immune system cells, called T cells, can kill tumor cells that express mesothelin. In addition, studies in both animals and humans have shown that antibodies directed against mesothelin protein can shrink tumors.

In the new study, the research team genetically engineered human T cells to target human mesothelin. To produce them, a modified virus was used as a delivery vehicle, or vector, to transfer synthetic genes to T cells. These genes directed the production of hybrid, or chimeric, proteins that can recognize and bind to mesothelin and consequently stimulate the proliferation and cell-killing activity of the T cells. In laboratory studies, the team found that the engineered T cells proliferated and secreted multiple cytokines when exposed to mesothelin. Cytokines are proteins that help control immune functions. The cells also expressed proteins that made them resistant to the toxic effects of tumors and their surrounding tissues.

To study the effects of the engineered T cells on tumor tissue, the researchers implanted human mesothelioma cells underneath the skin of mice. About six weeks later, when tumors had formed and progressed to an advanced stage, the engineered T cells were administered to the mice. Direct injection of the T cells into tumors or into veins of the mice resulted in disappearance or shrinkage of the tumor.

“Based on the size of the tumors and the number of cells administered, we estimate that one mesothelin-targeted T cell was able to kill about 40 tumor cells,” said study leader Carl H. June, M.D., Professor of Pathology and Laboratory Medicine and director of Translational Research at Penn's Abramson Cancer Center. “This finding indicates that small doses of these cells may have potential in treating patients with large tumors. Clinical trials are being developed to investigate this approach in patients with mesothelioma and ovarian cancer.”

The study appears online the week of February 9 in the Proceedings of the National Academy of Sciences.

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Adapted from materials provided by University of Pennsylvania School of Medicine.

Source

Genetic Code of Common Cold Cracked

99 rhinoviruses now sequenced, could lead to new treatments, researchers say HealthDay

Thursday, February 12, 2009

THURSDAY, Feb. 12 (HealthDay News) -- Today's medical breakthrough: a cure for the common cold.

Well, researchers are reporting what could at least be a significant step in that direction: the genetic codes of the 99 known viruses responsible for those pesky nasal infections.

"There has been brilliant work done trying to synthesize compounds against the common cold," said Dr. Stephen B. Liggett, director of the cardiopulmonary genomics program at the University of Maryland, and senior author of a report on the discoveries published in the Feb. 12 online issue of Science. "But we have not been working with a full knowledge of the genetics of rhinoviruses. Now that we have the full complement of known ones, we see there are subfamilies of rhinoviruses clustering together. The hope is that there could be a drug for each subfamily."

Liggett and the other researchers in the project used virus samples collected by nasal swabs in doctors' offices over two decades and sent to the American Type Culture Collection, a private nonprofit organization headquartered in Virginia. Some rhinovirus genomes had already been sequenced from those samples. The current study adds 80 new full genome sequences, showing their relationships.

"We made a family tree," Liggett said. "The major branches are going to be fixed. We have sequenced rhinoviruses from 10,000 individuals at different locations in the United States, and we see major branches in the trees, with lots of little twigs in the tree."

The viruses are still evolving, Liggett said. "We compared some samples taken in 2005 with some from the 1970s, and found a fair number of mutations," he said. "But the major evolutionary structure of the tree is not going to change."

Rhinoviruses can't change too much, Liggett explained. "If they mutate to become super virulent, they destroy the cells they live in. They might become less deadly and narrow down the window they operate in. We don't understand that window very well."

There is hope that a careful study of the viral genomes will reveal one central point of attack that could be exploited by drug makers. "What we would like is a single Achilles' heel for all the viruses that we have found so far, and we could attack in that direction," Liggett said.

But the viruses are found to have impressive powers of change. The study shows that some human rhinoviruses result from the exchange of genetic material from two separate strains infecting the same person. Such recombination had not been thought possible for rhinoviruses.

That recombination is one reason why a vaccine against the common cold appears to be impossible, said Ann C. Palmenberg, director of the Institute for Molecular Virology at the University of Wisconsin, and lead author of the sequencing effort. The viruses just keep changing too much.

A second reason is that the rhinoviruses do their dirty work on the mucosa, the outer lining of the inner nose, Palmenberg said. "We're not good at making vaccines that give mucosal protection," she said.

But there is hope for a single drug that would be effective against many rhinoviruses, Palmenberg and Liggett agreed. "Drugs have the probability of taking out multiple serotypes at one time," Palmenberg said.

Who would develop such a drug? "The most likely scenario is that a small biotechnology company would begin the work, and as they made progress, they would get the attention of a larger drug company," Liggett said. "Occasionally, a biotechnology can keep the ball rolling all the way through. It will be interesting to see how this unfolds."

Source

This is right up NanoViricides alley!

Researchers Create Cancer-Killing Smart Bomb From Plant Virus

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A North Carolina State University team has created a new cancer-killing smartbomb candidate out of a plant virus, like the one shown here. Advantages of this approach include its biocompatibility and ample cargo space (the spherical void inside the outer shell). (Source: Stanford Synchrotron Radiation Laboratory)

"Someone set us up the bomb"

One of the hottest areas of research in nanotechnology is the creation of tiny "smart bombs" which are able to latch on to a specific cell and deliver a chemical payload. While such devices would be useful to treat a variety of disease, cancer is their primary target.

Researchers at North Carolina State University have used modified plant viruses to create the latest version of the smart bomb. By selectively targeting specific cells in the body for payload delivery, it could greatly reduce the effects of toxic treatments like chemotherapy on healthy cells, while increasing the efficacy of killing cancer cells.

For the project Dr. Stefan Franzen, professor of chemistry, and Dr. Steven Lommel, professor of plant pathology and genetics, modified a typical non-toxic plant virus. The gutted virus has a "cargo space" of 17 nanometers, in which it typically carries its DNA. This space can be filled with drugs to deliver to cells. The virus is coated in small proteins, called signal peptides, which help it find its targets.

By modifying these signal peptides to match those in cancer cells (but not in healthy cells) accepting deliveries, the virus can be injected into the cell and deliver its payload. Professor Franzen says his team’s smart bomb is better than past designs, stating, "We had tried a number of different nanoparticles as cell-targeting vectors. The plant virus is superior in terms of stability, ease of manufacture, ability to target cells and ability to carry therapeutic cargo."

The plant virus uses calcium concentrations to trigger the release of its cargo. When in the bloodstream or intercellular matrix the high calcium concentration prevents the cargo from being released. However, inside cells the calcium concentration drops, and the virus dumps its cargo.

Professor Lommel describes another perk of using the virus, stating, "Another factor that makes the virus unique is the toughness of its shell. When the virus is in a closed state, nothing will leak out of the interior, and when it does open, it opens slowly, which means that the virus has time to enter the cell nucleus before deploying its cargo, which increases the drug's efficacy."

As with other efforts, a critical key is to identify chemical markers on cancerous cells and compare them with those in healthy cells. Much work needs to be done before proper marker proteins can be added to these smart bombs to effectively target cancer. In other words -- efforts like this one have built a powerful weapon; it just needs its targeting system completed.

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Source

Hybrid Carbon Nanotube Metal Oxide Arrays to Improve Lithium Battery Technology

Need to store electricity more efficiently? Put it behind bars.

That's essentially the finding of a team of Rice University researchers who have created hybrid carbon nanotube metal oxide arrays as electrode material that may improve the performance of lithium-ion batteries.

With battery technology high on the list of priorities in a world demanding electric cars and gadgets that last longer between charges, such innovations are key to the future. Electrochemical capacitors and fuel cells would also benefit, the researchers said.

The team from Pulickel Ajayan's research group published a paper this week describing the proof-of-concept research in which nanotubes are grown to look – and act – like the coaxial conducting lines used in cables. The coax tubes consist of a manganese oxide shell and a highly conductive nanotube core.

"It's a nice bit of nanoscale engineering," said Ajayan, Rice's Benjamin M. and Mary Greenwood Anderson Professor in Mechanical Engineering and Materials Science.

"We've put in two materials – the nanotube, which is highly electrically conducting and can also absorb lithium, and the manganese oxide, which has very high capacity but poor electrical conductivity," said Arava Leela Mohana Reddy, a Rice postdoc researcher. "But when you combine them, you get something interesting."

That would be the ability to hold a lot of juice and transmit it efficiently. The researchers expect the number of charge/discharge cycles such batteries can handle will be greatly enhanced, even with a larger capacity.

"Although the combination of these materials has been studied as a composite electrode by several research groups, it's the coaxial cable design of these materials that offers improved performance as electrodes for lithium batteries," said Ajayan.

"At this point, we're trying to engineer and modify the structures to get the best performance," said Manikoth Shaijumon, also a Rice postdoc. The microscopic nanotubes, only a few nanometers across, can be bundled into any number of configurations. Future batteries may be thin and flexible. "And the whole idea can be transferred to a large scale as well. It is very manufacturable," Shaijumon said.

The hybrid nanocables grown in a Rice-developed process could also eliminate the need for binders, materials used in current batteries that hold the elements together but hinder their conductivity.

Posted February 9th, 2009

Source

Graphene for the Green Grid

Thursday, February 05, 2009

Ultracapacitors that store more could help the grid run smoothly.

By Katherine Bourzac

Graphene power: Graphene Energy hopes that graphene electrodes such as this one will increase the energy-storage capacity and power output of ultracapacitors. This image, which shows the edge of a graphene electrode, was made with a scanning-electron microscope.
Credit: Meryl Stoller

Integrating irregular sources of renewable energy, such as wind and solar, with the electrical grid, while keeping power output steady, is going to be a big challenge. Energy-storage devices called ultracapacitors could help by storing sudden surges of power. But much will depend on developing a new generation of ultracapacitors with enough storage capacity to meet the likely demand.

Graphene Energy, a startup based in Austin, TX, hopes that ultracapacitors with electrodes made of graphene--sheets of carbon just an atom thick--will be the solution. The storage capacity of an ultracapacitor is limited only by the surface area of its electrodes, and graphene offers a way to greatly increase the area available.

Ultracapacitors store energy electrostatically, instead of chemically, as in batteries. During charging, electrons come to the surface of one electrode, and electron "holes" form on the surface of the other. This draws positive ions in an electrolyte to the first electrode and negative ions to the second. By contrast, the chemical reactions used to charge batteries limit the speed with which they can be charged and eventually cause the electrode materials to break down. Ultracapacitors can be charged and discharged very rapidly, in seconds rather than minutes, and can be recharged millions of times before wearing out.

However, ultracapacitors currently on the market can't match batteries for energy density, so they're mostly used in hybrid systems alongside batteries or for niche applications. Because these devices can handle a rapid influx of large amounts of energy, they're often used to recover energy--for example, when a city bus breaks or a gantry crane lowers its cargo. Ultracapacitors employed in this way have reduced by 40 percent the energy needed by some cranes used in Japanese ports. A few power tools, including an electric drill, take advantage of the rapid recharging ability of ultracapacitors.

Graphene Energy hopes to open up new ultracapacitor applications by developing devices with far higher power output. These ultracapacitors could perhaps be used to regulate surges in the electrical grid or to power hybrid transportation vehicles. The company has $500,000 in seed funding to commercialize graphene ultracapacitors developed by Rodney Ruoff, a professor and chair of mechanical engineering at the University of Texas at Austin. Ruoff is a cofounder of Graphene Energy and also serves as the company's technology advisor.

Existing ultracapacitors use electrodes made from activated carbon--a porous, charcoal-like material that has a very high surface area. Activated carbon stores charge in tunnel-like pores, and it takes about one second for it to travel in and out. This is very fast compared with the fastest batteries, but activated carbon has a limited power output.

To make the graphene for its electrodes, Ruoff's team starts by putting graphite oxide in a water solution. This causes the material to flake into atom-thin sheets of graphene oxide. Next, the oxygen atoms are removed, leaving the graphene behind. So far, Ruoff's lab has made graphene ultracapacitors that match the performance of those made using activated carbon. With further refinements, he says, they should outperform activated carbon, although the steps that his company is taking to achieve this remain secret.

Based on a description of the graphene ultracapacitors published last September in the journal Nano Letters, John Miller of JME, a research and consulting firm that specializes in electrochemical capacitors, says that it should indeed be possible to improve their performance. The graphene electrode described in this paper is "wadded into a ball like a crumpled piece of paper," says Miller. "You don't have full access to the surface."

If Graphene Energy can grow the electrodes in vertical arrays, like a row of perfectly flat sheets of paper standing on edge, Miller says that the power output could be increased dramatically. In this arrangement, every single carbon atom would be exposed and able to store energy, with virtually no waiting time for the charge to travel down the tunnels found in activated carbon.

However, in addition to improving the performance of its ultracapacitors, Graphene Energy must also develop a method for making them at larger scales--a common challenge across all graphene research.

Dileep Agnihotri, CEO of Graphene Energy, says that the company hopes to test its first prototype product incorporating graphene electrodes by the end of this year.

Another group of researchers hopes to make better ultracapacitor electrodes using carbon nanotubes--rolled-up tubes of graphene that have many of the same properties. "I think both approaches can work in principle," says Joel Schindall, a professor of electrical engineering and computer science at MIT who is working on the nanotube electrodes. "The key will be getting the growth process right, then working on ways to manufacture it in a cost-effective manner."

http://www.technologyreview.com/business/22062/?nlid=1752&a=f

NexBio

NexBio - another possible company cohort for NanoViricides:

Fludase® (DAS181) is a broad-spectrum drug candidate for the prophylaxis and treatment of respiratory infections by all types of influenza virus, including the types of virus that may cause a potential influenza pandemic, as well as all types of parainfluenza virus. Fludase® is currently in phase I clinical development, and has successfully completed its First-In-Man trial.

MECHANISM OF ACTION: FLUDASE® BLOCKS IFV ENTRY INTO CELLS

Fludase® is a recombinant fusion protein (see figure 1) that inactivates viral receptors on the cells of the human respiratory tract, thereby preventing influenza and other viruses such as parainfluenza from both infecting the human body and amplifying in already-infected individuals.

In the human respiratory tract, cell-surface sialic acids act are the host cell receptors for all influenza A and B and parainfluenza viruses. Fludase® works by inactivating these sialic receptors in the airway epithelium, therefore preventing viral entry into cells.
Source

Finally, I would like to express my gratitude for the support of the National Institutes of Health and the National Institute of Allergy and Infectious Disease, without which our critical research would not be possible.

Mang Yu
CEO
Source

NexBio is a five-year-old biotechnology company located in San Diego, California, founded to create and commercialize novel, broad-spectrum biopharmaceuticals to prevent and treat current and emerging life-threatening human disease. All funding to date has been from the National Institutes of Health in the form of grants and contracts, totaling ~$63 million.
Source

• NexBio lives off grants, year after year, $63 Million in 5 years, so far.
• I note that NexBio uses the sialic acid stuff in their virus fighting efforts. They block the virus from attaching to the cell it is targeting by interfering with the sialic acid attachment points on cells. They block those attachment points with a covering chemical so the virus has no way to attach to the cell it seeks. I think they do their thing on the cells themselves and do not do anything to the virus directly. NNVC does attack the virus directly and immobilizes it by making the cide look to the virus like a cell with the same sialic acid attachment points that the virus attaches to and becomes trapped unable to infect any cells themselves.

• I found this:

Hemagglutinin, displayed at left, is one of two virally-coded integral envelope proteins of the influenza virus. Hemagglutinin is responsible for host cell binding and subsequent fusion of viral and host membranes in the endosome after the virus has been taken up by endocytosis. In the first step of infection it binds to sialic acid residues of glycosylated receptor proteins on target cell surfaces.
Source

• So...I guess NNVC targets the sialic acid binding bits on the virus (making the virus think the cide particles are the host cells by presenting sialic acid binding sites for the virus to attach to), whereas NexBio tagets the sialic acid itself on the cell that the virus is looking to bind to and covers it so the virus can't find it. Two sides of the same coin perhaps?

• Re the government giving grants:
• Wouldn't it make sense to combine the likes of NNVC and NexBio into one grant? More bang for the buck? They certainly are similar!

• Re NexBio funding:

Corporate funding to date has been entirely non-dilutive, consisting of five grants totaling $13M, together with a BAA
Contract for $49.8M to support Fludase(R) development, all from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.
Source

• Re NexBio IP:

United States Patent Application 20050004020
Kind Code A1
Yu, Mang ; et al. January 6, 2005

Broad spectrum anti-viral therapeutics and prophylaxis

Abstract

The present invention provides new compositions and methods for preventing and treating pathogen infection. In particular, the present invention provides compounds having an anchoring domain that anchors the compound to the surface of a target cell, and a therapeutic domain that can act extracellularly to prevent infection of the target cell by a pathogen, such as a virus. Preferred target cells are epithelial cells. The invention provides compositions and methods for preventing viral diseases, such as influenza, using compounds having anchoring domains that can bind target cells linked to enzymatic activities that can act extracellularly to interfere with viral infection of target cells. The invention also provides compositions and methods for preventing viral diseases such as influenza using compounds having anchoring domains that can bind target cells linked to protease inhibitors that can act extracellularly to interfere with viral infection of target cells.
Source

United States Patent Application 20050112751
Kind Code A1
Fang, Fang ; et al. May 26, 2005

Novel class of therapeutic protein based molecules

Abstract

The present invention provides new compositions and methods for preventing and treating pathogen infection. In particular, the present invention provides compounds having an anchoring domain that anchors the compound to the surface of a target cell, and a therapeutic domain that can act extracellularly to prevent infection of a target cell by a pathogen, such as a virus. The present invention also comprises therapeutic compositions having sialidase activity, including protein-based compounds having sialidase catalytic domains. Compounds of the invention can be used for treating or preventing pathogen infection, and for treating and reducing allergic and inflammatory responses. The invention also provides compositions and methods for enhancing transduction of target cells by recombinant viruses. Such compositions and methods can be used in gene therapy.
Source

2 results found in the Worldwide database for:
NexBio as the applicant
(Results are sorted by date of upload in database)

1 TECHNOLOGY FOR THE PREPARATION OF MICROPARTICLES in my patents list
Inventor: MALAKHOV MICHAEL [US] ; FANG FANG [US] Applicant: NEXBIO INC [US] ; MALAKHOV MICHAEL [US] (+1)
EC: IPC:

Publication info: WO2009015286 (A2) — 2009-01-29

2 TECHNOLOGY FOR PREPARATION OF MACROMOLECULAR MICROSPHERES in my patents list
Inventor: MALAKHOV MICHAEL P [US] ; FANG FANG [US] Applicant: NEXBIO INC [US]
EC: A61K9/14; A61K9/00M20B; (+9) IPC: A61K9/16; A61K38/16; A61K38/48; (+3)

Publication info: KR20080090525 (A) — 2008-10-08
Source

• Re relevance?

• Not sure but interesting insofar as viral infection is attacked using targeting on cells. And, more importantly, if NexBio can garner $63million in government grants for their R&D and manufacture can we be far behind?

Refs:
WIPO
WO/2009/015286
WO/2007/114881

• Note (From WO/2007/114881):

As used herein, an emulsion is defined as a colloid of two immiscible liquids, a first liquid and a second liquid, where the first liquid is dispersed in the second liquid. As used herein, surfactants (or "surface-active agents") are chemical or naturally occurring entities which, when dissolved in an aqueous solution, reduce the surface tension of the solution or the interfacial tension between two or more phases in solution. The surfactant molecules generally are amphiphilic and contain hydrophilic head groups and hydrophobic tails. The surfactant molecules can act as stabilizers and/or improve flowability characteristics of the microparticles provided herein.

• Note as to particle sizing (From WO/2007/114881):

The geometric size of microspheres produced by the two methods was assessed by light microscopy and found to be essentially identical (range of 1.5 - 3.0 microns) [1500nm-3000nm] for both methods.