Archive for the ‘Metastases’ Category

New Drug Could Slow Spread of Prostate Cancer

Comments Off
Posted 21 Apr 2012 — by James Street
Category KBU2046, Lung Metastases, Metastases, Prostate Cancer
 April 20, 2012

In mice, stops disease from spreading to nearby tissues and bone

Jessica Berman

Scientists report they have developed a drug that can prevent prostate cancer from spreading to nearby tissues and bone, increasing the chances of successful treatment.

The experimental compound doesn’t cure prostate cancer. It contains the disease so more traditional cancer therapies, such as surgery and radiation, have a chance to work.

Raymond Bergan is director of experimental therapeutics at the Robert H. Lurie Comprehensive Cancer Center at Northwestern University in Illinois, where the drug was developed.

Using breast cancer as an analogy, Bergan says it’s not the original cancer that’s lethal, but its spread or metastasis.

“The relevance of that is life versus death, literally,” he says. “If the cancer is localized, it’s very treatable, curable. If the cancer has spread throughout the body, it will take her life. We can treat it, but it will take her life.”

The new drug, called KBU2046, is a small molecule that attaches to tumor proteins involved in metastasis and disables them, so they can’t travel to distant organs. Bergan says it’s like turning off a switch that tells the cells to keep moving all the time.

Bergan and his colleagues transplanted aggressive human prostate cancer cells into mice, and then fed them the drug for five weeks. The compound prevented metastasis of the cancer to the lungs, a frequent site of tumor spread in men with prostate cancer.

Toxicity studies showed the compound is safe. Unlike other cancer therapies, which can cause significant side effects, investigators say the experimental drug spares healthy cells, causing minimal side effects.

Bergan is confident that KBU2046 will work to contain other cancers as well.

“We don’t think it’s specific to prostate cancer. We’ve done some early tests with other cancer cells in the laboratory and it appears to stop them from moving.”

Bergan stresses that drugs developed using animal models don’t always work in humans, and he’s looking forward to trials involving cancer patients.

Phase II study of ecteinascidin 743 in heavily pretreated patients with recurrent osteosarcoma.

Comments Off
Posted 15 Mar 2012 — by James Street
Category Metastases, Osteosarcoma, Osteosarcoma Outcomes, Relapse, Trabectedin, Yondelis
Cancer. 2003 Aug 15;98(4):832-40.

Source

Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.

Abstract

BACKGROUND:

Recurrent osteosarcoma is a drug-resistant disease with a dismal prognosis. The objective of this Phase II study was to evaluate the activity of ecteinascidin 743 (ET-743) as a salvage therapy in these patients.

METHODS:

Patients with recurrent osteosarcoma who had received standard chemotherapeutic agents were eligible. ET-743 was administered at a dose of 1500 microg/m(2) as a 24-hour infusion every 3 weeks. Pharmacokinetic studies were performed during the first cycle.

RESULTS:

Twenty-five patients were enrolled, 23 of whom were assessable for response (median age of 18 years; range, 12-67 years). The median number of previous chemotherapeutic agents was five (range, three to eight previous agents). Sixty-one cycles were administered (median number of cycles per patient was 2; range, 1-9 cycles per patient). Three patients (12%) achieved minor responses (49% 36% and 25%, respectively). Fifteen patients (60%) developed a transient elevation of hepatic transaminases (Grade 3 or 4 [according to the National Cancer Institute Common Toxicity Criteria]), which was not cumulative. Grade 3 or 4 neutropenia and thrombocytopenia were observed in 12 patients (48%) and 6 patients (24%), respectively. The mean area under the curve (AUC) in 4 patients experiencing Grade 4 toxicity (76.4 +/- 29.3 ng x hr/mL) was significantly greater (P = 0.034) than that in those for whom the most severe toxicity was Grade 3 (39.5 +/- 17.2 ng x hr/mL [n = 12]) or Grade 1-2 (52.6 +/- 15.6 ng x hr/mL [n = 5]). There were no other significant correlations found between pharmacokinetic variables and patient characteristics, toxicity, or therapeutic response.

CONCLUSIONS:

ET-743 was found to be well tolerated in heavily pretreated osteosarcoma patients but had limited antitumor activity as a single agent. The combination of ET-743 with cisplatin or doxorubicin should be considered.

Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11563

Fundraiser planned for unexpected cancer survivor

Comments Off
Posted 11 Mar 2012 — by James Street
Category Complementary and Alternative Medicine, Gerson Diet, Gerson Diet, Local Recurrence, Lung Metastases, Metastases, Osteosarcoma
by Kelli Easterling

16-year-old Jonathan Hernandez has been battling metastic osteosarcoma, bone cancer that doctors said had spread to his lungs, for about two years.

When he was diagnosed, doctors told his parents that the cancer was in an advanced stage and that the prognosis was typically very poor, according to his mother, Diana Janica, a Spanish teacher at Richmond Senior High School.

“The doctors told us that if he received chemotherapy treatment, he would maybe live for two years,” said Janica. “After that, it was likely his kidneys and liver would shut down.”

Janica’s husband, Pablo Hernandez, discovered a unique treatment option when talking to his sister, a doctor in Columbia, South America.

She told the frantic parents about the Gerson Institute. The Institute uses a whole-body approach to healing that supposedly boosts the body’s immune system, and other defenses, to cure cancer, arthritis, heart disease and allergies.

Since their son had only a small chance of surviving the chemo treatments, the couple decided they had to go out on a limb and try something different than they were being offered at the hospitals.

“They were basically telling me he was going to die, but that he should do chemotherapy anyway,” said Janica.

The Gerson Diet is high in vitamins, minerals and fluids, and low in sodium and fats. The typical daily diet consists of three full vegetarian meals and 10-13 glasses of fresh raw juice. All ingredients must be organic, fresh and washed in distilled water, to avoid excess fluoride exposure. The diet is supplemented with things like niacin, potassium compound and flax seed oil. The strictest form of this diet will continue for two to four years.

It is a very demanding program to stick with. On top of the sometimes outrageous costs of purchasing fresh, organic produce, the juice has to be made fresh, every hour from 8 a.m.-7 p.m. This means his father stays home with him during the day, and works at night once his mother is home from school.

Today, Jonathan’s mother is happy to report that Jonathan’s cancer is officially shrinking.

“We went to Chapel Hill December 29 and the oncologists said the lesions in his lungs are getting smaller,” said Janica. “His bone cancer is regressing. They told me when he was diagnosed that he should be dead by now! We are so happy. This type of cancer does not usually get smaller – this is amazing. For the first time, the oncologist did not mention chemotherapy.”

Jonathan reported that he has been seeing his doctor every three months, but now the doctors have told him his appointments can be scheduled six months apart.

“That means I’m doing really good,” he said. “My breathing is at 100 percent now. And I’ve gotten a lot taller – I’m almost six feet tall now.”

Jonathan is home schooled because he has a weaker immune system and can’t take the risk of being exposed to germs.

“I miss school a lot because I have to figure out a lot of the work on my own,” he said. “I’d like other kids to know that they’re lucky to be able to go to class and have their teachers there.”

While health insurance would help with the costs of conventional cancer therapy, it doesn’t acknowledge this type of treatment. The burden of paying about $2,500 a month in supplies fell squarely on the family – until community members stepped in.

Richmond Senior High faculty, staff and students have been there for the family, spreading the word and helping any way they can. Churches and neighbors soon found out about the unique situation and have also been helping along the way.

A new fund raising committee has formed, and is planning an all-day event and barbecue fundraiser for the the boy at Pat’s Kitchen, in Rockingham.

“I’m their neighbor, and this is their only child,” said committee member, Susanne McInnis. “My heart just goes out to them. They were brought here as missionaries from their home, and when Jonathan was diagnosed they had no family here to turn to. The community is their family now.”

Pat’s Kitchen hosted a fundraiser for Jonathan last year, and raised $9,700 for Nature’s Own, the supplier of Jonathan’s organic fruits and vegetables.

“We’ve put too much into Jonathan getting better to give up on him now,” said Marshall Berry, co-owner of Pat’s Kitchen. “We’ve been hosting benefits here since we opened for business, and the Lord has blessed us tremendously. We are happy to be able to give back.”

“We’re excited about Jonathan’s progress,” said McInnis. “At one time, he couldn’t breath very good, but recently he was able to play the flute at church.”

Encouraged by Jonathan’s progress over the past two years, McInnis teamed with Sandra Parker, Pam Dillman, Betty Brigman, Debbie Webb, Lisa Britt and Pat Britt to plan another event at Pat’s Kitchen to help pay for Jonathan’s food.

On Saturday, March 24 from 11 a.m. – 5 p.m., Pat’s Kitchen will host a pork barbecue and fried chicken plate sale – dine in or carry out – for $7 per plate.

Delivery is available for orders of five or more.

“Marshall won the Kansas City Cook-off with his barbecue, and his fried chicken won a blue ribbon at the State Fair,” said McInnis.

There will be live entertainers at the restaurant all day, including original member of beach music group O’Kaysions, Ed Dement, singing “I’m a Girl Watcher,” a self-proclaimed cousin of Elvis Presley, doing spot-on impersonations, Brookes and Dunn impersonators, other country music impersonators, gospel singers and beach tunes.

There will be an auction at 5 p.m., hosted by Iron Horse Auction.

Plate tickets are available for sale now at Pat’s Kitchen, or plates can be purchased the day of the event.

Raffle tickets are also available now for $1. A 32” flat-screen television from R.W. Goodman Co. and neighbors and a gas grill will be raffled off March 24 at the event.

“So many businesses have donated for the auction, I can’t even thank them all,” said McInnis.

For more information about the event, or to donate auction items or funding to Jonathan’s cause, contact 910-895-1009, 910-206-1009 or 910-895-0683.

“The Lord is good,” said Janica. “The Lord is teaching us to live by faith, this is an adventure! We are trying to enjoy this time while we are seeing what the Lord has next for Jonathan. This has helped Jonathan to focus on the future and what the Lord has for him in the following hours, days and years. He can really enjoy little details in life as miracles for him now since he did not expect to live this long.”

— Staff Writer Kelli Easterling can be reached at 910-997-3111, ext. 18, or by email at keasterling@heartlandpublications.com.

High serum alkaline phosphatase cooperating with MMP-9 predicts metastasis and poor prognosis in patients with primary osteosarcoma in Southern China

Comments Off
Posted 16 Feb 2012 — by James Street
Category ALP, Lung Metastases, Metastases, MMP-9, Molecular Osteosarcoma Studies, Osteosarcoma

Background Osteosarcoma is a malignant tumor with high ability to form invasion and metastasis. Identifying prognostic factor in osteosarcoma is helpful to select those patients for more aggressive management.

Our study evaluated serum alkaline phosphatase (ALP) cooperating with matrix metalloproteinase-9 (MMP-9) as an important prognostic predictor for local recurrence and distant metastasis of osteosarcoma.Methods 177 cases were included from the osteosarcoma patients treated at 1st Affiliated Hospital of Sun Yat-sen University (1999-2008). Pre-chemotherapy serum ALP (pre-ALP) were studied and correlated with tumor recurrence, lung metastasis and patient survival.

MMP-9 protein in tumor tissues was detected by immunohistochemistry and correlated with pre-ALP level.Results Pre-ALP were partitioned into normal, high, and very high groups, in each group the incidence of metastases was 12.2%, 21.2% and 34.6%, respectively (p=0.007). In the three groups the mean disease-free survival (DFS) was 57+/-3.15, 28+/-3.57 and 14+/-3.35 months, respectively (p<0.001); overall survival (OS) was 92+/-26.89, 39+/-8.61 and 17+/-5.07 months, respectively (p<0.001).

By multivariate analysis, elevated serum pre-ALP were associated with shorter DFS (p=0.018) and OS (p=0.031). If elevated ALP levels decreased after clinical treatment, the incidence of lung metastasis rate decreased (p=0.028); DFS and OS were both prolonged (p<0.001).

Pre-ALP was also positively correlated with MMP-9 expression (p=0.015) in tumor tissue.Conclusions Pre-ALP was an independent prognostic factor for the survival of osteosarcoma patients in south China, and correlated with MMP-9 expression and lung metastasis. ALP can also serve as a prognostic marker for treatment, and merit large-scale validation studies.

Author: Ju HanBicheng YongCanqiao LuoPingxian TanTingsheng PengJingnan Shen
Credits/Source: World Journal of Surgical Oncology 2012, 10:37

MIT Researchers Target Cancer’s Most Deadly Phase

Comments Off
Posted 25 Dec 2011 — by James Street
Category Lung Metastases, Metastases, metastases
Author: Marcia Stone : Posted to Decoded Science on December 24, 2011 at 2:12 pm
Invasive human breast cancer: Image courtesy of Robert Weinberg

If malignant cells could be kept from wandering about the body and colonizing new sites, the number of cancer deaths would be cut by about 90%. However, it’s become apparent in recent years that metastasis isn’t a simple, random process; it’s a well-orchestrated sequence of events most of which are largely unknown.

In fact, “[metastasis] remains the most poorly understood component of cancer pathogenesis,” says Robert A. Weinberg, PhD, Professor of Biology at the Massachusets Institute of Technology (MIT) in Cambridge. Professor Weinberg helped identify ras, the first human oncogene, in the 1970s and a few years later the first known tumor suppressor gene, Rb.  Most recently, Weinberg’s team at the MIT Whitehead Institute for Biomedical Research created the first genetically-defined human cancer cells.

Robert A. Weinberg Discusses his Latest Research with Colleagues at the SKI in December

Understanding how metastasis works has great clinical potential and this is why, Weinberg told cancer experts at the Sloan-Kettering Institute’s President’s Research Seminar, held at the Rockefeller Research Laboratories (RRL) in New York City on December 14th, the scientists in his laboratory are vigorously investigating this “most enigmatic” aspect of cancer.

For starters, the Weinberg and colleagues have organized the complex metastatic cascade into two major parts: first, the physical translocation of a cancer cell from its primary tumor to a distant site and second, colonization.  An understanding of the first step, physical dissemination, is in sight he says. However, colonization is far more complicated and may require several more years of research before the traits a cancer cell needs to implant and grow in alien soil are fully understood.

Nonetheless, knowing how a cancer cell escapes the confines of a tumor and explores adjacent environments is expected to prove important for preventing metastasis in people with early cancer lesions. Designing effective therapies for patients with already-established disease will have to wait.

“Tumor-Initiating” Cancer Stem Cells (CSCs) 

“The discovery of CSCs has forced  major rethinking of tumor biology,” says Weinberg, adding that a variety of cancer-associated traits once ascribed to tumor cell populations as a whole are now known to be associated with one or another subpopulations of CSCs.  CSCs exist side-by-side with normal self-renewing stem cells (SCs); but unlike SCs, CSCs have greatly enhanced tumor-initiating potential thus the ability to seed new cancers.

One critical role of CSCs in metastasis is obvious, Weinberg notes; they act as founder cells, spawning vast numbers of descendants. Indeed, the very traits that define CSCs – self-renewal and tumor initiating ability – also define successful metastasis. However CSCs have other less well-recognized attributes necessary for metastasis: motility, invasiveness, and a heightened resistance to apoptosis. This implies that a multifaceted biological program exists within a primary tumor empowering some cancer cells to escape and start colonies elsewhere. It also suggests that cancer is a systemic disease long before any of the malignant cells begin migrating.

The Epithelial-to-Mesenchymal Transition

Embryonic tissue differentiates with a program known as the EMT, shorthand for “epithelial-to-mesenchymal transition,” which is also activated during cancer invasion and metastasis.  “The EMT enables both normal and neoplastic epithelial cells to acquire mesenchymal cells attributes such as motility, invasiveness, and a resistance to apoptosis,” Weinberg says. Carcinoma cells with mesenchymal attributes can not only physically disseminate, they can self-renew which enables them to seed new environments. Long-term exposure to stroma-associated signals also helps keep cells in the mesenchymal/stem-cell state in a self-sustaining, stable fashion.  Additionally, their resistance to programmed cell death or apoptosis is, “surely critical to the ability of the migrating cells to survive the rigors of the voyage” from primary tumors to distant sites, he adds.

Moreover, primary carcinomas, the Weinberg team’s target cancers, release signals that recruit inflammatory cells to the tumor. This both helps assemble a highly functional, tumor-supporting environment, or stroma, and keeps some of the cells in a biologically-abnormal activated state.  However, while conceptually appealing, Weinberg cautions that the role of EMT in metastasis remains unproven.

Cancer Colonization 

Pelvis with bone metastasis: Image courtesy of Diagnostic pathology

Although EMT programs seem critical for the physical dissemination of carcinoma cells, they don’t appear capable of initiating and sustaining colonization.  Colonization, Weinberg emphasizes, seems to entail a far more complex set of phenomena, and have a relatively small number of unifying general principles. The tissue microenvironment of a primary tumor is likely to differ markedly from that of a secondary site which requires the wandering cancer cell to make substantial adaptive changes in order to survive and multiply. These changes appear to be dictated by both the microenvironment of the primary tumor as well as that of the landing site.

In general, says Weinberg, colonization is an extremely inefficient process, and most cancer cells that successfully translocate from a primary to a secondary site don’t survive more than 24 hours in their new home. This is good news because the outcome of successful colonization is a rapidly expanding macrometastasis that disseminates a shower of secondary metastases. Moreover, cancer cells being dispatched from the successful new colony are likely to be invested with the kinds of genetic programs that make it easier for them to migrate and colonize a variety of tissues.  These cells are so much more fit than their ancestors that the “throngs of secondary metastases derived from the initial metastatic shower soon eclipse the initiating metastasis that spawned them,” Weinberg stresses.

Sources:

Robert A. Weinberg, Ph.D. 2011 Calloway Lecture: EMT, Cancer Stem Cells and Malignant Progression. December 14, 2011.

Chaffer, C. L., Weinberg, R. A. A Perspective on Cancer Cell Metastasis. Science: 331:1559-1564, 25 March 2011. Accessed December 24, 2011.

Mani, S. A., Guo, W., Liao Mai-Jing, et al. The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells. Cell: 133, 704-715, 16 May 2008.

Mukherjee, S. The Emperor of All Maladies: A Biography of Cancer. New York City. Scribner. (2010). ISBN 978-1-4391-0795-9.

 

Vitamin D could help in fighting pediatric bone cancer

Comments Off
Posted 17 Dec 2011 — by James Street
Category Dog Osteosarcoma, Local Recurrence, Lung Metastases, Metastases, Osteosarcoma, Vitamin D

Posted by Laura HerringDecember 16, 2011 at 9:05 a.m.

A study by a group of Kansas University researchers found that vitamin D can cause cancerous bone cells to turn to normal bone cells.

The findings, which were published in the Journal of Orthopaedic Research, could lead to a new treatment in fighting pediatric bone cancer, which has a survival rate of 60 percent to 70 percent.

Recent studies have shown vitamin D can inhibit the growth of malignant cells in breast, prostate and colon cancer. Kim Templeton, an orthopedic surgeon at Kansas University Hospital, was among the experts on a panel that discussed vitamin D research and cancer. She was surprised that none of the studies or trials included the effect of vitamin D on osteosarcoma, a malignant bone tumor that mainly affects children and adolescents.

“It’s the most common type of bone cancer in kids and teenagers and vitamin D is critical to bone health,” she said. So an interdisciplinary team at the Kansas University Medical Center came together to study how vitamin D affects bone cancer. The team used cancerous tumor cells to do the research.

“My question was if the tumor recognizes Vitamin D and if it would help control the cells,” Templeton said. In the laboratory tests, not only did the cancerous cells recognize the vitamin D, but it prevented the osteosarcoma cells from replicating as quickly and promoted the growth of normal bone cells.

“What should happen and what does happen (in the lab) is always two different things,” Templeton said. “So, I was happy it turned out the way we thought it would.”

The findings are important for a cancer who hasn’t seen the treatment methods or rate of survival change in the past 20 to 25 years. Most osteosarcoma patients undergo 10 weeks of chemotherapy before the tumor is removed.

The findings suggest that a normal size dose of vitamin D could become another tool in the treatment of osteosarcoma. Unlike chemotherapy, normal doses of vitamin D don’t have any negative side effects and it is inexpensive.

Before clinical trials on humans can began, researchers would have to test the effects of vitamin D on animals, which might include large dogs since they have a high rate of osteosarcoma.

Templeton said the findings don’t suggest people should start taking vitamin D to prevent bone cancer. Although that is a connection researchers might study in the future.

By Christine Metz

N-acetyl-cysteine (NAC)–is an anticarcinogenic and antimutagenic agent

Comments Off
Posted 21 Nov 2011 — by James Street
Category Antiagiogenesis, Metastases, metastases, N-acetylcisteine

N-acetyl-cysteine (NAC)–is an anticarcinogenic and antimutagenic agent; it inhibits IL-6 as well as invasion and metastasis of malignant cells
N-acetyl-cysteine (NAC) is the acetylated precursor of the amino acids L-cysteine and reduced glutathione. Historically, it is used as a mucolytic agent in respiratory illnesses as well as an antidote for acetaminophen hepatotoxicity, but more recently its credits have grown. Animal and human studies have shown it to be a powerful antioxidant and a potential therapeutic agent in the treatment of cancer (Bongers et al. 1995; van Zandwijk 1995).

The biological value of NAC is attributed to its sulfhydryl group, while its acetyl-substituted amino group offers protection against oxidative and metabolic processes (Bonanomi et al. 1980; Sjodin et al. 1989). In vitro studies showed NAC to be directly antimutagenic and anticarcinogenic; in vivo, NAC inhibited mutagenicity of a number of mutagenic materials (De Flora et al. 1986, 1992).

NAC has both chemopreventive and therapeutic potential in malignancies arising in the lung, skin, breast, liver, head, and neck (van Zandwijk 1995; Izzotti 1998). NAC is effective in inhibiting tumor cell growth in melanoma, prostate cells, and astrocytoma cell lines (the latter is a primary tumor in the brain) (Albini et al. 1995; Arora-Kuruganti et al. 1999; Chiao et al. 2000). Neovascularization (new blood vessel growth) is crucial for tumor mass expansion and metastasis. NAC inhibited invasion and metastasis of malignant cells by up to 80% by preventing angiogenesis (De Flora et al. 1996).

A number of cancers express IL-6 and other potentially dangerous cytokines. NAC inhibited (in a dose-dependent manner) the synthesis of IL-6 by alveolar macrophage (Munoz et al. 1996; Gosset et al. 1999).

Peak plasma levels of NAC occur approximately 1 hour after an oral dose; 12 hours after dosing, it is undetectable. Despite a relatively low bioavailability (4-10%), research has shown NAC to be clinically effective (Borgstrom et al. 1986). A suggested NAC therapeutic dosage is usually in the range of 600 mg per day.

Modified Citrus Pectin (MCP)–retards cancer growth and metastasis

Comments Off
Posted 21 Nov 2011 — by James Street
Category Diet and Prostate Cancer, Lung Metastases, Metastases, Modified Citrus Pectin (MCP), Prostate Cancer, PSA testing

Modified citrus pectin (MCP), also known as fractionated pectin, is a complex polysaccharide obtained from the peel and pulp of citrus fruits. Through pH and temperature modifications, the pectin is broken down into shorter, nonbranched, galactose-rich, carbohydrate chains. The shorter chains dissolve more readily in water, making them better absorbed than ordinary, long-chain pectin. The short polysaccharide units afford MCP its ability to access and bind tightly to galactose-binding lectins (galectins) on the surface of certain types of cancers. By binding to lectins, MCP is able to powerfully address the threat of metastasis (Strum et al. 1999).

In order for metastasis to occur, cancerous cells must first bind or clump together; galectin is thought responsible for much of cancer’s metastatic potential by providing the binding site (Raz et al. 1987; Guess et al. 2003; Pienta et al. 1995). MCP appears small enough to access and bind tightly with galectins, inhibiting (or blocking) aggregation of tumor cells and adhesion to surrounding tissue (Kidd 1996). Deprived of the capacity to adhere, cancer cells fail to metastasize.

Men with prostate cancer who took 15 grams of MCP a day had a slowdown in the doubling time of their PSA levels. (Lengthening of doubling time represents a decrease in the rate of cancer growth.) Interestingly, rats injected with prostate adenocarcinoma and given MCP (in drinking water) showed a significant reduction in metastasis (compared to control animals), although the primary tumor was unaffected. According to Dr. Kenneth Pienta (leader of the Michigan Cancer Foundation), MCP may be the first oral method of preventing spontaneous prostate cancer metastasis (Pienta et al. 1995; Guess et al. 2003).

As with prostate adenocarcinoma, research shows that metastasis of breast cancer cell lines requires aggregation and adhesion of the cancerous cells to tissue endothelium in order for it to invade neighboring structures (Glinsky et al. 2000). To test the anti-adhesive properties of MCP, researchers evaluated (in an in vitro model) breast carcinoma cell lines MCF-7 and T-47D. The study concluded that MCP countered the adhesion of malignant cells to blood vessel endothelium and subsequently inhibited metastasis (Naik et al. 1995). MCP decreased metastasis of melanoma to the lung by more than 90% in laboratory animals (Platt et al. 1992).

Because MCP is a soluble fiber, no pattern of adverse reaction has been recorded in the scientific literature, apart from a self-limiting loose stool at high doses. MCP dosages are usually expressed in grams, with a typical adult dose ranging from 6-30 grams divided throughout the day. MCP’s apparent safety and proven antimetastatic action, and the lack of other proven therapies against metastasis appear to justify its inclusion in a comprehensive orthomolecular anticancer regimen (Kidd 1996). Pecta-Sol is the brand name of the original modified citrus pectin (MCP. The dosage for Pecta-Sol is about 15 grams a day.

Tyrosine Isomers Mediate the Classical Phenomenon of Concomitant Tumor Resistance

Comments Off
Posted 19 Nov 2011 — by James Street
Category Metastases, metastases, Tyrosine
  1. Raúl A. Ruggiero1,
  2. Juan Bruzzo1,
  3. Paula Chiarella1,
  4. Pedro di Gianni1,
  5. Martín A. Isturiz1,
  6. Susana Linskens2,
  7. Norma Speziale2,
  8. Roberto P. Meiss3,
  9. Oscar D. Bustuoabad1, and
  10. Christiane D. Pasqualini1

+ Author Affiliations


  1. Authors’ Affiliations:1División Medicina Experimental, Academia Nacional de Medicina; 2Facultad de Farmacia y Bioquímica, UBA; and 3Instituto de Estudios Oncológicos, Academia Nacional de Medicina, Buenos Aires, Argentina
  1. Corresponding Author:
    Raúl A. Ruggiero, División Medicina Experimental, Academia Nacional de Medicina, Pacheco de Melo 3081 (1425), Buenos Aires, Argentina. Phone: 54-11-4805-3411; Fax: 54-11-4803-9475; E-mail: ruloruggiero@yahoo.com.ar

Abstract

Concomitant tumor resistance (CR) is a phenomenon originally described in 1906 in which a tumor-bearing host is resistant to the growth of secondary tumor implants and metastasis. Although recent studies have indicated that T-cell–dependent processes mediate CR in hosts bearing immunogenic small tumors, manifestations of CR induced by immunogenic and nonimmunogenic large tumors have been associated with an elusive serum factor. In this study, we identify this serum factor as tyrosine in its meta and ortho isoforms. In three different murine models of cancer that generate CR, both meta-tyrosine and ortho-tyrosine inhibited tumor growth. In addition, we showed that both isoforms of tyrosine blocked metastasis in a fourth model that does not generate CR but is sensitive to CR induced by other tumors. Mechanistic studies showed that the antitumor effects of the tyrosine isoforms were mediated, in part, by early inhibition of mitogen-activated protein/extracellular signal-regulated kinase pathway and inactivation of STAT3, potentially driving tumor cells into a state of dormancy. By revealing a molecular basis for the classical phenomenon of CR, our findings may stimulate new generalized approaches to limit the development of metastases that arise after resection of primary tumors, an issue of pivotal importance to oncologists and their patients. Cancer Res; 71(22); 7113–24. ©2011 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).

  • R.A. Ruggiero, M.A. Isturiz, N. Speziale, O.D. Bustuoabad, and C.D. Pasqualini are members of Research Career of CONICET; Juan Bruzzo and Paula Chiarella are Fellows of CONICET.

  • Received February 17, 2011.
  • Revision received August 16, 2011.
  • Accepted September 2, 2011.

Key protein fuelling growth of cancer identified

Comments Off
Posted 03 Nov 2011 — by James Street
Category Lung Metastases, Metastases, Understanding Cancer

Last Updated: Monday, October 31, 2011,17:11

Washington: Scientists have identified a key mechanism of metastasis that could lead to blocking tumor growth if their findings are confirmed.

Lead researcher David Waisman, Ph.D., professor in the Departments of Biochemistry and Molecular Biology and Pathology, and Canada Research Chair in Cancer Research at Dalhousie University in Nova Scotia, detailed the key role the macrophage cell surface protein S100A10 plays in allowing macrophages to move to the site of tumor growth – a process that is essential to tumor development.

Waisman said the findings are an example of the complicated biology of cancer.

“We used to think that the only cells that mattered in a tumor were the cancer cells, and that’s it, but now we are beginning to see that other cells must collaborate with cancer cells to drive tumor growth and permit an evolution of the cancer cells into metastatic cells. This change is what causes poor prognosis and ultimately what kills the patient,” he said.

Waisman and colleagues discovered that tumors do not grow without macrophage assistance. These macrophages must come from the blood or from other locations in the tissues. How they are able to move through the tissues or from the blood supply into the tumor had always been a mystery.

These macrophages need to chew their way through the tissue that forms a barrier around the growing tumor in order to move into the tumor site and combine with the cancer cells. The researchers found on the outside surface of the macrophage is a protein called S100A10, which enables the macrophage to remove the tissue barriers retarding migration to the tumor site.

Theoretically, blocking either the macrophages or S100A10 chemically could slow, or even stop, tumor growth, Waisman said.

The study was recently published in the journal Cancer Research.

← Previous Entries