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We publish the note of Prof. Massimo Bonucci about the article “Ipilimumab” on the “Daily Health”

Here it is my comment on the article came out in April about the monoclonal antibody “Ipilimumab”.
It’s a very important signal on the path of integration between therapies. Ipilimumab stimulates so much T4 lymphocytes that attack all “foreign” cells of our body; it means that the combined use with an antineoplastic such as Fotemustine may increase the action.
That’s what we say when speaking about the Immune System to increase the feedback by using anticancer drugs.

This can be done with a monoclonal antibody, the Ipilimumab or with other natural substances, such as the mistletoe, the micotherapy, the low dose immune therapy or the microimmunetherapy.
The difference is the rapidity of the response which is greater with the monoclonal antibody and the side effects which are more with the latter.
The continuous use of natural immune stimulants could be the path after cycles use of the monoclonal antibody.
Massimo Bonucci M.D.
President A.R.T.O.I.


Live Streaming for ARTOI – I.S.S . Congress

Dear User,

We are pleased to renew the invitation to participate at the “1st  Integrative Oncology Congress” next November 6–7, in Rome.

The Conference, organized by the A.R.T.O.I. Association and the National Institute of Health, will be held at the Istituto Superiore di Sanità, Aula Pocchiari, Viale Regina Elena 299, Rome.

If you cannot attend the event, you can follow the conference via web, with the opportunity to actively interact with the speakers.

By accessing the browser from your pc you can attend in live the event, listen to the speeches of the speakers and guests, see the supporting materials as it is displayed in the room and also interact during conversations through chat live to make questions.
If you want to participate by videoconference, we ask you to fill out the form below with your name, surname and e-mail address where you’ll receive the instructions for the access.

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Accetto la policy per il trattamento dati 

Circulating tumor cells

The reality on this new method that can help to more accurately hit the neoplastic disease.
The discovery of specific genetic alterations in malignant tumors has opened new directions in cancer therapy. The knowledge on the function of oncogenes and tumor proteins has substantially contributed to the understanding of the molecular and cellular principles of malignant tumors.

Based on these principles, the molecular analysis of the genes involved in the onset and progression of human cancers are now considered needful in order to find an appropriate and a more personalized treatment. This result can be reached by a new method able to detect cancer cells: circulating malignant cells.

Studies of neoplastic tumor cells (CTC) currently concern the recognition and prognostic prediction. In fact it was found that they exist and they often have different gene expression, therefore they are potentially more aggressive. So, their knowledge may determine a different pharmacological treatment.

Here’s the real news. To know if there are and what can be effective to lock them. There are labs that do this activity. Unfortunately, not in Italy. Or rather, in Italy there are scientific institutions, Padua is an example, can do it but currently they move around the predictive and not curative field.

Let’s try to figure out where you can get with this method.

The DNA in normal cells hosts the hereditary information, genes. Genes acts as process control such as growth, cell division and programmed cell death (apoptosis). In tumors, the cells are abnormal, show damages and alterations of the DNA, with the result of uncontrolled growth and cell proliferation. Initially the cancer cells divide and proliferate locally. But when the tumor grows bigger and acquires additional genetic alterations, can grow beyond the local border and some cells become metastatic.

The modern molecular biology techniques allow us to recognize the molecular markers that will give us the detection of CTCs.

Consequently, many molecular markers are available for the detection of circulating tumor cells in blood.

It is possible to isolate tumor cells from the peripheral blood of patients. In genetics we can identify and characterize these so-called circulating tumor cells (CTC) and separate patients at high risk and low risk.

Besides, in the CTC can be measured factors of drug resistance, which provide important information for the creation and optimization of personalized therapy.

This information can influence decisions about:

  • early initiation of therapy or supportive treatment
  • targeted therapy of the individual patient
  • identification of drug resistance

Molecular diagnosis of CTCs in the blood allows the identification of cancer patients, probably at a higher risk of recurrence and metastasis. These patients may benefit from additional adjuvant therapies.

Molecular analysis is able to give indications for the determination of the expression of drug targets and markers of chemo-resistance in tumor cells.

After surgical removal of the primary tumor, antiblastic therapy should reduce the number of CTCs. The discovery of the CTCs and the study of molecular parameters will direct us to a more targeted therapy.

Furthermore, the tumor cells are often released very soon from the primary tumor into the blood, prior to surgery. These cells may be genetically different from most of the cells of the primary tumor mass. Whereas most of the cells of the primary tumor are not able to produce metastases, only the cells that survive after got into the circulation are potentially dangerous for the formation of metastases. Therefore, the control of such cells is essential to avoid that the disease will become generalized.

What is done in the CTCs should be done also on primary tissue, so as to use the appropriate chemotherapy to reduce the tumor mass and make it operable (neoadjuvant therapy).

The determination of factors of resistance and metabolic properties of tumor cells may provide important information for the selection of an appropriate treatment. Many anti-cancer drugs are known metabolic enzymes, whose differential expression in tumor cells can influence the effect of therapy. A treatment option that is essential for cancer is chemotherapy. They exist for each type of tumor different schemes of chemotherapy (drugs or combinations of drugs). The effectiveness of them is usually determined by clinical studies and schemes that show statistically the best success rates. However, individual patients may respond differently to treatment and it is a difficult task for the clinician to choose the most appropriate of the available treatment regimens. The chemo sensitivity test can help to select the drugs most likely to be effective than others for each individual patient.

The expression of these genes is determined by the technical precision real-time quantitative PCR. An advantage of this strategy is that cancer cells do not have to be cultured or sub cultured in the laboratory. It is known that the properties of cancer cells can change rapidly during propagation in the laboratory and can no longer represent the in vivo situation.

From the academic literature it is known that the expression of genes that metabolize the drug is able to influence the action of the drug on tumor cells. Some drugs act directly on specific cellular molecule, called target drug. An effective response of these drugs requires the presence of the target drug in the cells, which may be evaluated by measuring the expression of the target gene of drugs.

Several anticancer drugs (e.g. cyclophosphamide, capecitabine, irinotecan, dacarbazine) are virtually inactive in its main form and need to be activated in the body, for example by liver enzymes. Such drugs are rather problematic to verify ex-vivo on tumor tissues. However, it will be studied the chemo sensitivity directly on this cells without having an enzymatic activation.

What types of cancer can be tested?

The test is realizable with any type of cancer (e.g. lung, colon, breast, ovary,
cervix, prostate, stomach, gastric, esophagus, liver …), mesothelioma or melanoma. You can also test the synovial sarcoma. However, other types of sarcoma (such as liposarcoma, leiomyosarcoma, chondrosarcoma …) gave lower success rates for the isolation of tumor cells (<50%).
Test of tumors of the central nervous system (e.g. glioblastoma) is limited since in most cases it is not managed to isolate CTC, since these tumors rarely releasing cells in the blood. Haematological malignancies (e.g. Hodgkin’s and non-Hodgkin’s lymphoma, lymphomas at B-cells, myeloid and lymphocytic leukemia) can be analyzed. Test for multiple Myelom (MM) is not recommended as is often observed a detection rate at low content of MM.

Treatment with natural agents (Integrative treatment).

The concept of integrative medicine claims higher success rates if the conventional anti-cancer therapy (e.g. chemotherapy) is combined with a complementary treatment. The conventional therapy may be limited by the toxicity or tumor resistance. Many agents from natural sources have been shown to have antitumor activity. Moreover, some natural agents are able to modulate the enzymatic cellular functions that cause resistance to chemotherapy in cancer cells. The action of these substances might make chemoresistant tumor cells more sensitive to chemotherapy.

Drug-carrier molecules (e.g. MDR or MRP) can be induced in tumor cells by
chemotherapy. As a consequence, an increased efflux of drugs leads to multi-drug resistance in cancer cells which is a serious problem in the treatment of cancer. Natural agents such as curcumin or Haelan 951 (fermented soybean extract) are known modulators of MDR. Thus, there is a possible advantage in the use of these agents with chemotherapy in tumors showing the MDRphenotype.

Heat shock proteins (HSP) can make cancer cells heat resistant and resistant to some chemotherapeutic drugs. Quercetin is an inhibitor of the protein HSP27 (heat shock protein) and can be used for the treatment if tumors show high levels of HSP27.

It is possible to test the use of natural agents in combination with chemotherapy.

For many natural anti-cancer agents, have been described mechanisms of action and genetic testing able to provide useful advices for a correct application. In addition to conventional drugs of chemotherapy, numerous natural agents are also useful in the treatment of cancer. These agents can have anti-cancer activity by killing tumor cells directly, for example, by induction of apoptosis (programmed cell death). Others are reported as modulators of cellular functions which give chemo-resistance to tumor cells. In such cases, the use of appropriate natural agents may have a synergistic or so-called integrative action.

Today’s reality does not consider these studies. In many cases we could use more precise and anticancer drugs that can really damage cancer cells.

ARTOI is able to provide all the information on this method.

The Pharmacogenomics is our everyday life, both for the study of the person and for the study on cancer cells.

Calorie Restriction

Importance of nutrition in integrative therapy: calorie restriction.

Studies on the physical well-being related to nutrition are now on the agenda. There is no scientific and/or generalist journal that do not show the use of the diet to stay healthy. Lately, however, there are studies that not only inform us about the quality of the diet (which must be done by skilled and competent staff) but also the so-called “calorie restriction”. This can be understood not only with the reduction of calories, but even linked to fasting.

The calorie restriction starts up genetic mechanisms of repairing and modulation of DNA that lead to a gain of life also temporal or anti-aging. People who maintain a calorie restriction live better and longer. Often, those who are “overweight” have a higher frequency of inflammatory and autoimmune diseases degenerating into the tumor. It has been shown, however, that those who maintain a diet in calorie restriction live longer and with fewer injuries.

Besides, there are also some natural substances that help in this field.

As it has been seen that calorie restriction starts up a genetic mechanism linked to some genes, in particular a family called the Sirtuins including the more active the Sirt 1, it has been observed that the Quercetin, the Fisetina, the Stilbenes Piceatannol and Resveratrol stimulate this gene from 5 to 15 times. This means that better we use these substances, together with the lifestyle; the more we can get a head start on longevity and degenerative diseases to cancer.

Whereas the Stilbenes get with difficulty into human cells, for a “difficult passage” through cell membrane, any “form” that makes it suitable for the passage is welcome (the complex resveratrol-glycosidase or Polydatin or complex resveratrol-Bglucans).

A deepening of this matter would not help only patients already sick, but it would be a way to “prevent” many diseases and live longer.

For further information I suggest you to read the two annexes to which I refer.

rc-e-autofagi-bergamini Calorie Restriction and Sirtuins

Massimo Bonucci M.D.

President ARTOI

The video of the III International Congress of Integrative Oncology

We publish the first video about the congress held in Rome on 2, 3 december 2011.

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FotoGalleria del II Congresso ARTOI

In questo articolo pubblichiamo una galleria fotografica relativa al II congresso Internazionale sulle Terapie Oncologiche Integrate, organizzato da ARTOI il 2/3 dicembre 2011

no images were found

8th International Conference of the Society for Integrative Oncology

It is concluded in Cleveland the Eighth Conference of the SIO (Society for Integrative Oncology). We publish a summary by Dr. Massimo Bonucci:The complete overview on the treatment of cancer has been the subject of extensive study during all three days of the 8th International Conference of the American Society for Integrative Oncology, held in Cleveland (Ohio, USA). The American Society for Integrative Oncology was founded about 10 years ago for the will of oncology colleagues, researchers and medical specialists who wanted to meet and discuss to find new solutions for the welfare of cancer patients.In this conference with the title “Innovating Integrative Oncology: New Science, New solution. The focus is the Patient” were addressed all the problems of cancer therapy and evaluated all the opportunities to improve the results.

An “open” vision of treatment, which has touched all areas: chemotherapy, radiotherapy, immunotherapy, phytotherapy, mind-body therapy, acupuncture.

One of the focuses of the conference was to assess the integration of natural substances with chemotherapy and radiotherapy. One concerned the “oxidative stress and cancer” and how antioxidants can or not interfere with the chemo and radiation. These reports were taken by Prof. Aggarwal of the MD Anderson Cancer Center in Houston. His data have helped to clarify how many natural substances and many antioxidants compounds (vitamins and minerals are an example) lead to an improvement in the quality of life as well as an adjuvant synergistic effect in combination with chemotherapy and radiotherapy. Curcumin and resveratrol are now considered molecules able to interact positively in combination with chemotherapy for various solid tumors (lung, breast, colon).

It was held discussion on clinical evidence of case studies of integrative cancer therapy and particularly appreciated the work done by Dr. Bonucci and his colleagues, Dr. Pastore and Dr. Ferrera on cases of peritoneal carcinomatosis from ovarian cancer.

Another focus was acupuncture, with its effectiveness in preventing and reducing several side effects of chemotherapy and radiotherapy.

Then, great interest has been given to therapy “mind-body” with all the psychosocial aspects but also its influence on the results as a possible “epigenetic” intervention on the tumor itself.

The hope is that all these innovations and scientific opportunities may become the heritage of all, doctors and patients, so we may give a greater knowledge and awareness to those who face, although in different locations, the neoplastic disease. 

The use of metformin as an adjuvant in integrative cancer treatment

Metformin is a hypoglycaemic drug that is used in conditions of hyperglycemia.
Besides its function to reduce the level of circulating sugars, it has been recently investigated and used as an agent able to interfere positively with the homeostasis and cell growth and as an agent suitable for the prevention of some cell changes that exist in cancer.
Metformin, in addition to some activity of modulation of the immune system and hormonal and body buoyancy, has shown even a blocking action of cell growth and a protective effect on vascular endothelium. Studies in basic research and also translated into therapeutic applications, have shown its primary action as a reducing agent of the neoplastic cell proliferative effect of insulin.
Further studies are underway to test its use as an adjuvant agent in cancer conditions and as a therapeutic agent to accompany any antiblastic chemotherapy or radiotherapy and hyperthermia.
Following one of the most important studies on the use of metformin.


J Diabetes. 2011 Feb 21. doi: 10.1111/j.1753-0407.2011.00119.x. [Epub ahead of print]

Metformin as an Antitumor Agent in Cancer Prevention and Treatment.

Li D.

Source: Department of Gastrointestinal Medical Oncology, The University of Texas MD

Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.



Recent epidemiological investigations conducted in diabetic cohorts and cancer

patients have found that metformin users have lower risks for cancer than

insulin or insulin secretogogue users. Studies conducted in various animal

tumor models and cancer cell lines have demonstrated that metformin prevents

tumor development or inhibits cell proliferation. In addition, a recent

clinical trial has shown that short-term use of metformin reduced aberrant

crypt foci (ACF) formation in nondiabetic patients with ACF. The antitumor

activity of metformin could be mediated through its regulatory effect on

hormonal, metabolic, and immune functions. Metformin achieves glycemic control

by reducing hepatic glucose production and increasing the muscle intake of

glucose, thus lowering levels of circulating glucose and, consequently, of

insulin. The major molecular targets of metformin are the liver kinase B1 (LKB1)

-5’AMP-activated protein kinase (AMPK) signaling and mTOR pathways, which are

central to the regulation of cellular energy homeostasis and play a crucial

role in the control of cell division and cell proliferation. Metformin has been

shown to improve endothelial function, decrease inflammatory activity, and

regulate immune function. Increasing experimental evidence provides a strong

biological rationale for metformin as an antitumor and chemopreventive agent.

Metformin is being tested as an adjuvant cancer therapy in clinical settings,

and use of metformin is recommended for all cases of type 2 diabetes without

contraindications. As we show in the current review, the chemopreventive value

of this drug is not restricted to diabetic or obese individuals.


Copyright © 2011 Ruijin Hospital and Blackwell Publishing Asia Pty Ltd.

Online the new website ARTOI

Rome, August 28, 2011

It is now online the new website of A.R.T.O.I.. It is possible that in these early stages you may encounter technical problems for which we apologize right now.

Please report any bug to: [email protected]

Thanks and enjoy reading,

The technical staff of A.R.T.O.I.

Chemotherapy and Phytotherapy

A new contribution to the combined and integrative use of chemotherapy and phytotherapy comes from this article that revisits the American studies of  mistletoe (Viscum album) and cùyclophosphamide or gemcitabine in case of solid tumors.

Read the article on Cancer Decisions®

Avastin (Roche) rejected by FDA

The FDA has announced that from the data obtained, serious side effects and poor results, the use of Avastin in breast cancer cases has not been approved. The pharmaceutical company Roche reiterated its willingness to do further study, however.

Read the article on Cancer Decisions®

L’ipertermia fa progressi in Texas

La notizia che viene riportata è molto importante, perché conferma quanto viene detto nel campo della integrazione oncologica molto tempo nei riguardi della Ipertermia: è una valida metodologia contro le neoplasie.

I colleghi del Texas Oncology, affiliati all’U.S. Oncology hanno acquistato le macchine per la Ipertermia capacitativa profonda, procedendo a sviluppare protocolli di trattamento oncologico.

Leggi l’articolo di “Cancer Decisions”