With the progress in genetics, the field of Oncology is bound to change. The volume of work done in the field of genetics as it relates to oncology, has moved this field from what it was, a research area, to center stage daily Oncology practice. Knowledge of CHOP and combination Etoposide -Cisplatin or even Taxol-Carboplatin indications, is shrinking in importance in the Ipilimumab and Crizotinib world. The thing is as we getting closer to actually cure cancer we have understood that knowing more about natural chemical pathways in the cell, and treating cancer based on this knowledge has yielded better results in response rates and disease free progression and sometimes in overall survival. This evidence has convinced most Oncologists that it is time to move to the Target therapy movement and brace our selves for the new "TARGETOLOGY" IN MEDICAL ONCOLOGY.
TARGETOLOGY IS NOT JUST THE STUDY OF CELLULAR TARGETS, it is the full command of treatments that address the law of Nature.
- Genes controlling DNA, DNA repair, DNA stability, and mechanisms therewith to maintain the integrity of the Nuclear Material and its Epigenetic environment.
- Genes involved in key the Cellular pathways and corollary pathways
- Genes of proliferation
- Genes of cellular metabolism amplification and regulator genes
- Genes of differentiation (Mesangial and endodermal transformation vs epithelialization)
- Genes of Cellular Adaptation
- Genes of electrical conduction and hidden pathways (Wnt, Notch)
- Genes controlling cellular adaptation
- Genes driving Metastasis, transport and membrane vacuole formation
- Genes of Receptors and cellular Adhesion
We should stress that the mechanisms used by the cell to impose the direction of Homeostasis based on flight or stay needs, response to environment stimuli, and sense of purpose imposed by the notch and cell differentiation. The notion of Core Binding Factor should be extended to all protein complexes imposing cellular Metabolism direction as it is evident that that's how the cell operates!
The notion that some Cancers use specific drivers that can be somewhat is easily identified (CML) vs cancers that are using regulator enzymes (certain Leukemias) or epigenic events, should be brought forth.
Some proliferative disorders find their driver effect in shifts in gene Methylation or splicing patterns rather than actually in changing or mutating genes. But clearly, most cancers come from a failure of receptors with subsequent increase of growth factors which end up imposing growth and Mutations in unwanted areas! Among the unrecognized mechanisms is deficiency of location of important effector proteins. In other words, failure in transport. Traffic has to go on from Membranes to Nucleus, transport failure for one reason or another, failure of vacuolization that allows exocytosis, function of Golgi apparatus and lysozome. Do not forget the Ribosome and Mitochondria! Some of the organelles are so important that they have their own genome!
The point is that it is time to now be reacquainted with cell biology to be an efficient Oncologist because that is where the answer is! Avoiding this fact will not cut it! It is the way to the future! Manipulating chemical destruction by using standard chemotherapy has failed to give more cures! We have met drug resistance and the power of cell adaptatio. It is past time to rethink our strategies and Targetology is here now and to stay!
Thursday, May 16, 2013
‘Truly Remarkable’ Response with Combination for Melanoma
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Drug & Reference Information
Combination immunotherapy with ipilimumab (Yervoy,
Bristol-Myers Squibb) and the investigational antibody drug nivolumab
(Bristol-Myers Squibb) has broken new ground in the treatment of
metastatic melanoma, producing durable tumor shrinkage in about half of
patients, according to results from a phase I study.
The objective response rate with the concurrent use of the 2 therapies was higher than seen in earlier trials of the 2 drugs used alone, said lead author Jedd Wolchok, MD, PhD, of the Memorial Sloan-Kettering Cancer Center, in New York City.
He spoke at a press briefing that precedes the 2013 annual meeting of the American Society of Clinical Oncology (ASCO).
In the new, dose-escalation, multiarm trial, the maximum doses of ipilimumab (3 mg/kg per day) and nivolumab (1 mg/kg per day), when given concurrently, yielded an objective response rate of 53% among 17 patients.
In earlier published trials, objective response rates were 11% for ipilimumab and 41% for nivolumab. At ASCO last year, nivolumab was hailed for "breaking the ceiling" for response rates seen in the past with immune therapies for cancer.
The ipilimumab/nivolumab concurrent regimen is now scheduled to be tested in phase 3 trials as a first-line treatment for patients with metastatic melanoma, starting in June 2013, Dr. Wolchok said.
A total of 52 of the 86 patients in the phase 1 trial were enrolled in concurrent therapy cohorts (of differing doses). Overall, 90% of these patients continued to have responses as of February 2013. All of the patients in the study, which is ongoing, have inoperable stage III and stage IV (metastatic) melanoma and had undergone up to 3 prior therapies.
The maximum dosage version of the concurrent therapy produced "rapid and profound" results, Dr. Wolchok said. A total of 7 of the 17 patients (41%) of these patients had > 80% tumor reduction at 3 months. Overall, about one third of all of the patients in concurrent treatment cohorts had > 80% tumor reduction.
"This is truly remarkable. This kind of response has not been seen with immunotherapy before," summarized Sandra Swain, MD, president of ASCO, who was not involved with the study but was a commentator at the press briefing. She is from the Washington Cancer Institute, in Washington, DC.
"This study is proof of principle that concurrent use of 2 immune checkpoint antibodies contains the treatment paradigm for advanced melanoma. It's very exciting," she continued.
Dr. Swain's comments refer to the fact that this is the first time that 2 immunotherapies have been used together in melanoma. Both belong to a new class of drugs, which employ "immune checkpoint blockade," meaning that they target immune system gatekeepers on immune cells, and "release the brakes" on the immune system to combat cancer, Dr. Wolchok said. Ipilimumab blocks CTLA-4, while nivolumab targets the protein PD-1.
"By blocking both CDLA-4 and PD-1 you allow for more robust immune cell activation," Dr, Wolchok added.
The complete response rate was 17% among the patients who received the ipilimumab/nivolumab concurrent therapy at maximum doses. However, among all of the patients in the trial, including those who received sequential therapy, the complete response rate was about 10%, he said.
In either case, the complete response rates were better than seen when the 2 agents are used alone (less than 3% for both ipilimumab and nivolumab), Dr. Wolchok said.
Because there have not been enough events to report yet, there is no median time to relapse in the phase 1 study. Neither of these immunotherapies are plagued by the consistent problem of drug resistance seen in the new targeted therapies for melanoma such as vemurafenib, Dr. Wolchok said.
The combination of ipilimumab and nivolumab is also being tested in non-small cell lung cancer and renal cell carcinoma.
Adverse Events "Manageable"
For all doses, the study protocol called for patients in concurrent cohorts to receive nivolumab and ipilimumab every 3 weeks for 4 doses, followed by nivolumab every 3 weeks for 4 doses. Then, at week 24, one concurrent combination treatment is administered every 3 months.
Dr. Wolchok reported that grade 3-4 side effects due to drug treatment occurred in 28 of 53 patients (53%) in the concurrent treatment cohorts. The adverse events were mostly related to immune-related inflammation. The most common were asymptomatic lab abnormalities: elevations of lipase (13%) and the liver enzymes AST (13%) and ALT (11%).
In the sequenced treatment cohorts, the toxicity was less intense. Grade 3-4 side effects due to drug treatment occurred in 6 of 33 patients (18%). The most common was asymptomatic elevation of lipase (6%).
The side effects in both the concurrent and sequenced treatment
cohorts were managed using "standard protocol algorithms," which
included steroids, Dr. Wolchok said.
There were no treatment-related deaths.
Dr. Wolchok downplayed adverse events seen in the trial. "We weren't surprised by the severity of the side effects or by anything new," he said. The adverse events were "no worse, no more frequent" than when the drugs are given alone, he said.
The study was supported by Bristol-Myers Squibb.
Dr. Wolchok reports being a consultant to Bristol-Meyers Squibb and research funding from the company. Coauthors include company employees.
American Society of Clinical Oncology (ASCO) 2013 annual meeting. Abstract 9012. To be presented June 2, 2013.
========================================================
AT CRBCM WE COMPLIMENT THE FOLKS AT MEDSCAPE FOR DOING AN EXCELLENT JOB KEEPING US INFORMED ABOUT THE EDGES OF ONCOLOGY!
The objective response rate with the concurrent use of the 2 therapies was higher than seen in earlier trials of the 2 drugs used alone, said lead author Jedd Wolchok, MD, PhD, of the Memorial Sloan-Kettering Cancer Center, in New York City.
He spoke at a press briefing that precedes the 2013 annual meeting of the American Society of Clinical Oncology (ASCO).
In the new, dose-escalation, multiarm trial, the maximum doses of ipilimumab (3 mg/kg per day) and nivolumab (1 mg/kg per day), when given concurrently, yielded an objective response rate of 53% among 17 patients.
In earlier published trials, objective response rates were 11% for ipilimumab and 41% for nivolumab. At ASCO last year, nivolumab was hailed for "breaking the ceiling" for response rates seen in the past with immune therapies for cancer.
The ipilimumab/nivolumab concurrent regimen is now scheduled to be tested in phase 3 trials as a first-line treatment for patients with metastatic melanoma, starting in June 2013, Dr. Wolchok said.
A total of 52 of the 86 patients in the phase 1 trial were enrolled in concurrent therapy cohorts (of differing doses). Overall, 90% of these patients continued to have responses as of February 2013. All of the patients in the study, which is ongoing, have inoperable stage III and stage IV (metastatic) melanoma and had undergone up to 3 prior therapies.
The maximum dosage version of the concurrent therapy produced "rapid and profound" results, Dr. Wolchok said. A total of 7 of the 17 patients (41%) of these patients had > 80% tumor reduction at 3 months. Overall, about one third of all of the patients in concurrent treatment cohorts had > 80% tumor reduction.
"This is truly remarkable. This kind of response has not been seen with immunotherapy before," summarized Sandra Swain, MD, president of ASCO, who was not involved with the study but was a commentator at the press briefing. She is from the Washington Cancer Institute, in Washington, DC.
"This study is proof of principle that concurrent use of 2 immune checkpoint antibodies contains the treatment paradigm for advanced melanoma. It's very exciting," she continued.
Dr. Swain's comments refer to the fact that this is the first time that 2 immunotherapies have been used together in melanoma. Both belong to a new class of drugs, which employ "immune checkpoint blockade," meaning that they target immune system gatekeepers on immune cells, and "release the brakes" on the immune system to combat cancer, Dr. Wolchok said. Ipilimumab blocks CTLA-4, while nivolumab targets the protein PD-1.
"By blocking both CDLA-4 and PD-1 you allow for more robust immune cell activation," Dr, Wolchok added.
The complete response rate was 17% among the patients who received the ipilimumab/nivolumab concurrent therapy at maximum doses. However, among all of the patients in the trial, including those who received sequential therapy, the complete response rate was about 10%, he said.
In either case, the complete response rates were better than seen when the 2 agents are used alone (less than 3% for both ipilimumab and nivolumab), Dr. Wolchok said.
Because there have not been enough events to report yet, there is no median time to relapse in the phase 1 study. Neither of these immunotherapies are plagued by the consistent problem of drug resistance seen in the new targeted therapies for melanoma such as vemurafenib, Dr. Wolchok said.
The combination of ipilimumab and nivolumab is also being tested in non-small cell lung cancer and renal cell carcinoma.
Adverse Events "Manageable"
For all doses, the study protocol called for patients in concurrent cohorts to receive nivolumab and ipilimumab every 3 weeks for 4 doses, followed by nivolumab every 3 weeks for 4 doses. Then, at week 24, one concurrent combination treatment is administered every 3 months.
Dr. Wolchok reported that grade 3-4 side effects due to drug treatment occurred in 28 of 53 patients (53%) in the concurrent treatment cohorts. The adverse events were mostly related to immune-related inflammation. The most common were asymptomatic lab abnormalities: elevations of lipase (13%) and the liver enzymes AST (13%) and ALT (11%).
In the sequenced treatment cohorts, the toxicity was less intense. Grade 3-4 side effects due to drug treatment occurred in 6 of 33 patients (18%). The most common was asymptomatic elevation of lipase (6%).
There were no treatment-related deaths.
Dr. Wolchok downplayed adverse events seen in the trial. "We weren't surprised by the severity of the side effects or by anything new," he said. The adverse events were "no worse, no more frequent" than when the drugs are given alone, he said.
The study was supported by Bristol-Myers Squibb.
Dr. Wolchok reports being a consultant to Bristol-Meyers Squibb and research funding from the company. Coauthors include company employees.
American Society of Clinical Oncology (ASCO) 2013 annual meeting. Abstract 9012. To be presented June 2, 2013.
========================================================
AT CRBCM WE COMPLIMENT THE FOLKS AT MEDSCAPE FOR DOING AN EXCELLENT JOB KEEPING US INFORMED ABOUT THE EDGES OF ONCOLOGY!
Creative Arts Therapies Improve QOL in Cancer Patients
Medicare Cuts Affect 80% of Oncology Practices, Says Survey
AUA and ASTRO Issue Joint Guidelines for Postsurgery RT
Should You Sell Drugs to Patients?
Xofigo (Radium-223) Approved for Prostate Cancer With Bone Mets
Drug & Reference Information
A novel radiopharmaceutical agent has been
approved by the US Food and Drug Administration (FDA) for use in the
treatment of prostate cancer.
The product, radium-223 dichloride (formerly known as alpharadin), will be marketed as Xofigo by Bayer for use in men with symptomatic metastatic castration-resistant prostate cancer that has spread to the bone but not to other organs. It is intended for men whose cancer has spread after medical or surgical therapy to lower testosterone, according to the FDA.
The FDA reviewed the product under its priority program, which provides for an expedited review of drugs that appear to provide safe and effective therapy when no satisfactory alternative therapy exists or offer significant improvement over products on the market. It was approved more than 3 months ahead of schedule.
Radium-223 dichloride "binds with minerals in the bone to deliver radiation directly to bone tumors, limiting the damage to the surrounding normal tissues," said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products at the FDA Center for Drug Evaluation and Research.
The product, administered once a month by intravenous injection, contains the heavy metal radium, which is taken up by osteoblasts and then emits alpha radiation. This causes double-strand DNA breaks that are lethal to the prostate cancer cell at the site of increased bone turnover induced by the cancer.
In a Medscape video commentary, Johann de Bono, MBChB, PhD, MSc, from the Royal Marsden NHS Foundation Trust in Sutton, United Kingdom, explained that radium-223 dichloride has minimal myelosuppression, is very well tolerated, and shows an impressive overall survival benefit.
The survival data come from the pivotal phase 3 ALSYMPCA trial, which involved 809 prostate cancer patients who were resistant to hormone treatment and had developed 2 or more bone metastases. All of the participants received standard treatment, but the men who also received radium-223 chloride lived significantly longer. An interim analysis revealed a median overall survival of 14.0 months, compared with 11.2 months (hazard ratio, 0.695; P = .00185), and the trial was stopped because of benefit.
An exploratory updated analysis confirmed the product's ability to extend overall survival, according to the FDA.
The most common adverse effects of radium-233 dichloride seen during clinical trials were nausea, diarrhea, vomiting, and swelling of the leg, ankle, or foot.
Radium-223 dichloride is highly targeted for bone metastases, so it is possible that it could be used in many different cancers that have spread to the bone, regardless of primary site, said lead investigator Chris Parker, MD, consultant clinical oncologist at the Royal Marsden Hospital in London, United Kingdom. Prostate cancer patients were studied in the first instance because this cancer has a high tendency to metastasize to the bone, Dr. Parker explained. About 90% of patients with advanced prostate cancer will develop bone metastases and, in many cases, there will not be any detectable metastases elsewhere in the body, he said.
The product, radium-223 dichloride (formerly known as alpharadin), will be marketed as Xofigo by Bayer for use in men with symptomatic metastatic castration-resistant prostate cancer that has spread to the bone but not to other organs. It is intended for men whose cancer has spread after medical or surgical therapy to lower testosterone, according to the FDA.
The FDA reviewed the product under its priority program, which provides for an expedited review of drugs that appear to provide safe and effective therapy when no satisfactory alternative therapy exists or offer significant improvement over products on the market. It was approved more than 3 months ahead of schedule.
Radium-223 dichloride "binds with minerals in the bone to deliver radiation directly to bone tumors, limiting the damage to the surrounding normal tissues," said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products at the FDA Center for Drug Evaluation and Research.
The product, administered once a month by intravenous injection, contains the heavy metal radium, which is taken up by osteoblasts and then emits alpha radiation. This causes double-strand DNA breaks that are lethal to the prostate cancer cell at the site of increased bone turnover induced by the cancer.
In a Medscape video commentary, Johann de Bono, MBChB, PhD, MSc, from the Royal Marsden NHS Foundation Trust in Sutton, United Kingdom, explained that radium-223 dichloride has minimal myelosuppression, is very well tolerated, and shows an impressive overall survival benefit.
The survival data come from the pivotal phase 3 ALSYMPCA trial, which involved 809 prostate cancer patients who were resistant to hormone treatment and had developed 2 or more bone metastases. All of the participants received standard treatment, but the men who also received radium-223 chloride lived significantly longer. An interim analysis revealed a median overall survival of 14.0 months, compared with 11.2 months (hazard ratio, 0.695; P = .00185), and the trial was stopped because of benefit.
Information from Industry
The most common adverse effects of radium-233 dichloride seen during clinical trials were nausea, diarrhea, vomiting, and swelling of the leg, ankle, or foot.
Radium-223 dichloride is highly targeted for bone metastases, so it is possible that it could be used in many different cancers that have spread to the bone, regardless of primary site, said lead investigator Chris Parker, MD, consultant clinical oncologist at the Royal Marsden Hospital in London, United Kingdom. Prostate cancer patients were studied in the first instance because this cancer has a high tendency to metastasize to the bone, Dr. Parker explained. About 90% of patients with advanced prostate cancer will develop bone metastases and, in many cases, there will not be any detectable metastases elsewhere in the body, he said.
Wednesday, May 15, 2013
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USING THE NOTCH IN CANCER TREATMENT
A NOVEL APPROACH,
The CRBCM is not claiming here to create anything new, Anti-Notch or Notch inhibitor are available and as reported have been used to no avail in Pancreatic cancer. But scientists are getting smarter by dissecting and discerning better various mechanisms of actions of drugs and pathogenesis of disease. And as you embark in this exercise, let me bring to your mind 2 interesting observations.
1. IL-2
This Cytokine attract White cell of the LYMPHOCYTE kind to the tumor
and sure enough kill Melanoma cells and Renal cancer cell.
wikipedia:
"Interleukin 2 (IL-2) is an interleukin, a type of cytokine signaling molecule in the immune system. It is a protein that regulates the activities of white blood cells (leukocytes, often lymphocytes) that are responsible for immunity."
2.Melanoma cells have a growth factor,
don't take my word but always trust wikipedia
"
Chemokine (C-X-C motif) ligand 1 (CXCL1) is a small cytokine belonging to the CXC chemokine
family that was previously called GRO1 oncogene, GROα, KC,
Neutrophil-activating protein 3 (NAP-3) and melanoma growth stimulating
activity, alpha (MSGA-α). In humans, this protein is encoded by the CXCL1 gene.[1]
================================================================
Now you have IL-2 lymphocytes
and Melanoma cell growth factor (MSGA-alpha) attracting Neutrophil
and as you dig deeper you will find that alpha is not the only type used by melanoma cell, there is a Beta, and gamma MSGA
but the point is that it attract Neutrophils. Is it to preclude or otherwise impede or shield it self from Lymphocyte attraction? And allows remember you don't grow by attracting enemies! These are friendly Neutrophils shielding the cell from detection! And the Melanoma cell knows what to do for them inherently though its NOTCH system! High dose IL-2 will bring lymphocytes here anyway.! the question is, COULD DISABLING THE NOTCH HERE PRIOR TO IL-2 INFUSION HELP IL-2 EFFECT IN MELANOMA?. COULD ADDING AN ANTI-NOTCH TO GEMZAR-ABRAXANE HELP IN PANCREATIC CANCER? ANTI-NOTCH ALONE ONLY OPEN THE CELL TO VULNERABILITY AND MAY NOT BE A TREATMENT ON ITS OWN WE BELIEVE, UNLESS THE LIFE OF THE CELL IS STRICTLY DEPENDING ON IT...AND ONLY IN BRAIN CELLS AND MYOCARDIUM WHERE ELECTRICITY CONDUCTION AND COORDINATION,SO DEPENDENT ON NOTCH, CAN HAVE THEIR LIFE IMPLICATED DEARLY WITH NOTCH!
We should mention also finishing here that for Melanoma cells, it appears that these Cytokines
help the cell with its immortality (which involves Telomeres and MTOR), growth and tumor formation by anchorage capacity), autocrine function and living in a "stress" mode without too much dependence from outside. they help the cell with chemotaxis (directing metastasis), angiogenesis (to ensure O2 supply and avoid too much stimulation of the Hypoxia induced factor/MTOR) and ensure Growth. Only an epigenetic intervention can curb significantly these autocrine growth factor. and curbing them we must to make a difference! (Look at the point of impact for targeted therapy, at each step, one may intervene!).
CAUTION
disabling the NOTCH may happen in normal cell, and now what? Brace for it!
also read
AND
A NOVEL APPROACH,
The CRBCM is not claiming here to create anything new, Anti-Notch or Notch inhibitor are available and as reported have been used to no avail in Pancreatic cancer. But scientists are getting smarter by dissecting and discerning better various mechanisms of actions of drugs and pathogenesis of disease. And as you embark in this exercise, let me bring to your mind 2 interesting observations.
1. IL-2
This Cytokine attract White cell of the LYMPHOCYTE kind to the tumor
and sure enough kill Melanoma cells and Renal cancer cell.
wikipedia:
"Interleukin 2 (IL-2) is an interleukin, a type of cytokine signaling molecule in the immune system. It is a protein that regulates the activities of white blood cells (leukocytes, often lymphocytes) that are responsible for immunity."
2.Melanoma cells have a growth factor,
don't take my word but always trust wikipedia
"
CXCL1
From Wikipedia, the free encyclopedia
| Chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
 PDB rendering based on 1mgs. |
|||||||||||
|
|||||||||||
| Identifiers | |||||||||||
| Symbols | CXCL1; FSP; GRO1; GROa; MGSA; MGSA-a; NAP-3; SCYB1 | ||||||||||
| External IDs | OMIM: 155730 MGI: 3037818 HomoloGene: 117693 GeneCards: CXCL1 Gene | ||||||||||
|
|||||||||||
| Orthologs | |||||||||||
| Species | Human | Mouse | |||||||||
| Entrez | 2919 | 330122 | |||||||||
| Ensembl | ENSG00000163739 | ENSMUSG00000029379 | |||||||||
| UniProt | P09341 | Q6W5C0 | |||||||||
| RefSeq (mRNA) | NM_001511 | NM_203320 | |||||||||
| RefSeq (protein) | NP_001502 | NP_976065 | |||||||||
| Location (UCSC) | Chr 4: 74.74 – 74.74 Mb |
Chr 5: 90.79 – 90.79 Mb |
|||||||||
| PubMed search | [1] | ||||||||||
Function
CXCL1 is secreted by human melanoma cells, has mitogenic properties and is implicated in melanoma pathogenesis.[2][3] CXCL1 is expressed by macrophages, neutrophils and epithelial cells,[4][5] and has neutrophil chemoattractant activity.[6][7] CXCL1 plays a role in spinal cord development by inhibiting the migration of oligodendrocyte precursors and is involved in the processes of angiogenesis, inflammation, wound healing, and tumorigenesis.[8][9][10][11] This chemokine elicits its effects by signaling through the chemokine receptor CXCR2.[8] The gene for CXCL1 is located on human chromosome 4 amongst genes for other CXC chemokines.[12] An initial study in mice showed evidence that CXCL1 decreased the severity of multiple sclerosis and may offer a neuro-protective function.[13]================================================================
Now you have IL-2 lymphocytes
and Melanoma cell growth factor (MSGA-alpha) attracting Neutrophil
and as you dig deeper you will find that alpha is not the only type used by melanoma cell, there is a Beta, and gamma MSGA
but the point is that it attract Neutrophils. Is it to preclude or otherwise impede or shield it self from Lymphocyte attraction? And allows remember you don't grow by attracting enemies! These are friendly Neutrophils shielding the cell from detection! And the Melanoma cell knows what to do for them inherently though its NOTCH system! High dose IL-2 will bring lymphocytes here anyway.! the question is, COULD DISABLING THE NOTCH HERE PRIOR TO IL-2 INFUSION HELP IL-2 EFFECT IN MELANOMA?. COULD ADDING AN ANTI-NOTCH TO GEMZAR-ABRAXANE HELP IN PANCREATIC CANCER? ANTI-NOTCH ALONE ONLY OPEN THE CELL TO VULNERABILITY AND MAY NOT BE A TREATMENT ON ITS OWN WE BELIEVE, UNLESS THE LIFE OF THE CELL IS STRICTLY DEPENDING ON IT...AND ONLY IN BRAIN CELLS AND MYOCARDIUM WHERE ELECTRICITY CONDUCTION AND COORDINATION,SO DEPENDENT ON NOTCH, CAN HAVE THEIR LIFE IMPLICATED DEARLY WITH NOTCH!
We should mention also finishing here that for Melanoma cells, it appears that these Cytokines
help the cell with its immortality (which involves Telomeres and MTOR), growth and tumor formation by anchorage capacity), autocrine function and living in a "stress" mode without too much dependence from outside. they help the cell with chemotaxis (directing metastasis), angiogenesis (to ensure O2 supply and avoid too much stimulation of the Hypoxia induced factor/MTOR) and ensure Growth. Only an epigenetic intervention can curb significantly these autocrine growth factor. and curbing them we must to make a difference! (Look at the point of impact for targeted therapy, at each step, one may intervene!).
CAUTION
disabling the NOTCH may happen in normal cell, and now what? Brace for it!
also read
Notch signaling contributes to lung cancer clonogenic capacity in vitro but may be circumvented in tumorigenesis in vivo.
Osanyingbemi-ObidiAND
Gamma-secretase inhibitor prevents Notch3 activation and reduces proliferation in human lung cancers.
Konishi J, Kawaguchi KS,Tuesday, May 14, 2013
THE POWERFUL MTOR INHIBITOR, NOT A WALK IN THE PARK!
AFINITOR is contraindicated in patients with
hypersensitivity to everolimus, to other rapamycin derivatives, or to
any of the excipients.
Noninfectious Pneumonitis:
- Noninfectious pneumonitis was reported in up to 19% of patients treated with AFINITOR. The incidence of Common Terminology Criteria (CTC) grade 3 and 4 noninfectious pneumonitis was up to 4.0% and up to 0.2%, respectively. Fatal outcomes have been observed
- If symptoms are moderate, patients should be managed with dose interruption until symptoms improve
- The use of corticosteroids may be indicated. For grade 4 cases, discontinue AFINITOR. Corticosteroids may be indicated until symptoms resolve
- For grade 3 cases, interrupt AFINITOR until resolution to grade ≤1
- AFINITOR may be reintroduced at a daily dose approximately 50% lower than the dose previously administered, depending on the individual clinical circumstances. If toxicity recurs at grade 3, consider discontinuation of AFINITOR
- The development of pneumonitis has been reported even at a reduced dose
Infections:
- AFINITOR has immunosuppressive properties and may predispose patients to bacterial, fungal, viral, or protozoal infections (including those with opportunistic pathogens). Localized and systemic infections, including pneumonia, mycobacterial infections, other bacterial infections, invasive fungal infections such as aspergillosis or candidiasis, and viral infections, including reactivation of hepatitis B virus, have occurred
- Some of these infections have been severe (eg, leading to respiratory or hepatic failure) or fatal
- Physicians and patients should be aware of the increased risk of infection with AFINITOR
- Treatment of preexisting invasive fungal infections should be completed prior to starting treatment
- Be vigilant for signs and symptoms of infection and institute appropriate treatment promptly; interruption or discontinuation of AFINITOR should be considered
- Discontinue AFINITOR if invasive systemic fungal infection is diagnosed and institute appropriate antifungal treatment
Oral Ulceration:
- Mouth ulcers, stomatitis, and oral mucositis have occurred in patients treated with AFINITOR at an incidence ranging from 44% to 86% across the clinical trial experience. Grade 3/4 stomatitis was reported in 4% to 9% of patients
- In such cases, topical treatments are recommended, but alcohol-, peroxide-, iodine-, or thyme-containing mouthwashes should be avoided
- Antifungal agents should not be used unless fungal infection has been diagnosed
Renal Failure:
- Cases of renal failure (including acute renal failure), some with a fatal outcome, have been observed in patients treated with AFINITOR
Geriatric Patients:
- In the randomized advanced hormone receptor-positive, HER2-negative breast cancer study, the incidence of deaths due to any cause within 28 days of the last AFINITOR dose was 6% in patients ≥65 years of age compared to 2% in patients <65 years of age
- Adverse reactions leading to permanent discontinuation occurred in 33% of patients ≥65 years of age compared with 17% in patients <65 years of age
- Careful monitoring and appropriate dose adjustments for adverse reactions are recommended
Laboratory Tests and Monitoring:
- Elevations of serum creatinine, proteinuria, glucose, lipids, and triglycerides, and reductions of hemoglobin, lymphocytes, neutrophils, and platelets, have been reported
- Renal function (including measurement of blood urea nitrogen, urinary protein, or serum creatinine), blood glucose, lipids, and hematologic parameters should be evaluated prior to treatment and periodically thereafter
- When possible, optimal glucose and lipid control should be achieved before starting a patient on AFINITOR
Drug-Drug Interactions:
- Avoid coadministration with strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole)
- Use caution and reduce the AFINITOR dose to 2.5 mg daily if coadministration with a moderate CYP3A4 and/or PgP inhibitor is required (eg, amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem)
- Avoid coadministration with strong CYP3A4 inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital); however, if coadministration is required, increase the AFINITOR dose from 10 mg daily up to 20 mg daily, using 5-mg increments
Hepatic Impairment:
- Exposure of everolimus was increased in patients with hepatic impairment
- For patients with severe hepatic impairment (Child-Pugh class C), AFINITOR may be used at a reduced dose if the desired benefit outweighs the risk. For patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment, a dose reduction is recommended
Vaccinations:
- The use of live vaccines and close contact with those who have received live vaccines should be avoided during treatment with AFINITOR
Embryo-Fetal Toxicity:
- Fetal harm can occur if AFINITOR is administered to a pregnant woman. Women of childbearing potential should be advised to use a highly effective method of contraception while using AFINITOR and for up to 8 weeks after ending treatment
Adverse Reactions:
- The most common adverse reactions (incidence ≥30%) were stomatitis (67%), infections (50%), rash (39%), fatigue (36%), diarrhea (33%), and decreased appetite (30%)
- The most common grade 3/4 adverse reactions (incidence ≥2%) were stomatitis (8%), infections (5%), hyperglycemia (5%), fatigue (4%), dyspnea (4%), pneumonitis (4%), and diarrhea (2%)
Laboratory Abnormalities:
- The most common laboratory abnormalities (incidence ≥50%) were hypercholesterolemia (70%), hyperglycemia (69%), increased aspartate transaminase (AST) concentrations (69%), anemia (68%), leukopenia (58%), thrombocytopenia (54%), lymphopenia (54%), increased alanine transaminase (ALT) concentrations (51%), and hypertriglyceridemia (50%)
- The most common grade 3/4 laboratory abnormalities (incidence ≥3%) were lymphopenia (12%), hyperglycemia (9%), anemia (7%), decreased potassium (4%), increased AST (4%), increased ALT (4%), and thrombocytopenia (3%)
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
Please see full Prescribing Information for AFINITOR.
Reference: 1. AFINITOR [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; August 2012.
KEEP UP WITH ME! FOR YOUR INFORMATION!
Recent cases and outbreaks of antibiotic resistant organisms, including methicillin resistant
Staphylococcus aureus (MRSA), Clostridium difficile infection (CDI), extremely-drug resistant tuberculosis (XDR-TB), and carbapenemase-resistant
Enterobacteriaceae (CRE), have shown that antibiotic resistance
represents a serious threat to public health. These organisms are
associated with high mortality rates and have the potential to spread
widely. They also represent a significant burden
to the health care system. To address this major public health threat,
the Indiana State Department of Health (ISDH), in collaboration with
many partners, has convened the Indiana Antibiotic Resistance Advisory
Committee.
Health
care providers and hospital administrators will receive a survey via
Survey Monkey in the coming weeks to measure knowledge, attitudes, and
beliefs regarding aspects
of antibiotic resistance. Responses to this survey will provide data
to describe antibiotic resistance in Indiana and allow the committee to
identify priorities. We look forward to your active collaboration as we
strive to mitigate antibiotic resistance
in Indiana. For additional information on management of multi-drug
resistant organisms in healthcare settings, visit
http://1.usa.gov/12sCPip.
Please see attached letter.
William C. VanNess II, MD
State Health Commissioner
FDA Approves First Companion Diagnostic for Lung Cancer
Topic Alert
Receive an email from Medscape whenever new articles on this topic are available.
Drug & Reference Information
The US Food and Drug Administration today announced the approval of the cobas EGFR Mutation Test, a companion diagnostic for the cancer drug erlotinib (Tarceva). This is the first FDA-approved companion diagnostic that can detect epidermal growth factor receptor (EGFR) gene mutations, which are present in approximately 10% of non–small cell lung cancers (NSCLCs).
The approval of this test comes at the same time as an expanded indication for erlotinib. The FDA has also announced a labeling change for erlotinib, and the drug is now indicated for first-line use in patients with metastasized NSCLC that tests positive for EGRF mutations. Until now, the official indication was second- or third-line use in advanced NSCLC.
"The approval of the cobas EGFR Mutation Test will allow physicians to identify non–small cell lung cancer patients who are candidates for receiving Tarceva as first-line therapy," said Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA's Center for Devices and Radiological Health, in a statement. "Companion diagnostics play an important role in determining which therapies are the safest and most effective for a particular patient."
The safety and effectiveness of the cobas EGFR Mutation Test was established with clinical data showing progression-free survival in NSCLC patients with specific types of EGFR mutations (exon 19 deletions or exon 21 L858R substitution mutations) for 10.4 months when they received erlotinib treatment, compared with 5.4 months for those who received standard therapy.
In the United States, erlotinib is currently the only drug available for use in EGFR-positive NSCLC, although elsewhere in the world, another similar drug is widely used: gefitinib (Iressa). A third drug in this class of EGFR tyrosine kinase inhibitors (TKIs), afatanib (Boehringer Ingelheim), is close to approval, with an FDA decision expected in July 2013. Afatanib will also have its own companion diagnostic test ( Therascreen EGFR PCR Kit, from Qiagen).
Using an EGFR TKI in the first-line treatment of EGFR-mutated NSCLC is recommended by several clinical guidelines, including the American Society of Clinical Oncology.
Patient outcomes are significantly better when compared with
chemotherapy, so much so that it "would be a tragedy not to use" an EGFR
inhibitor in an EGFR-positive patients, according to
one expert in the field, Edward Kim, MD, PhD, assistant professor of
medicine and director of clinical operations at the University of
Texas M.D. Anderson Cancer Center in Houston. To not know whether the
tumor is mutation-positive is not acceptable anymore, he added.
However, testing for mutations is not yet routine, and there are difficulties with obtaining lung cancer samples of sufficient size and quality, as well as disagreement over which is the best method for obtaining such samples, as recently reported by Medscape Medical News. In addition, there are issues with the costs of such testing, as outlined in a comment from a surgeon is response to that article.
The cobas EGFR Mutation Test is manufactured by the Roche Molecular Systems. Erlotinib is co-marketed by California-based Genentech, a member of the Roche Group and OSI Pharmaceuticals.
The approval of this test comes at the same time as an expanded indication for erlotinib. The FDA has also announced a labeling change for erlotinib, and the drug is now indicated for first-line use in patients with metastasized NSCLC that tests positive for EGRF mutations. Until now, the official indication was second- or third-line use in advanced NSCLC.
"The approval of the cobas EGFR Mutation Test will allow physicians to identify non–small cell lung cancer patients who are candidates for receiving Tarceva as first-line therapy," said Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA's Center for Devices and Radiological Health, in a statement. "Companion diagnostics play an important role in determining which therapies are the safest and most effective for a particular patient."
The safety and effectiveness of the cobas EGFR Mutation Test was established with clinical data showing progression-free survival in NSCLC patients with specific types of EGFR mutations (exon 19 deletions or exon 21 L858R substitution mutations) for 10.4 months when they received erlotinib treatment, compared with 5.4 months for those who received standard therapy.
In the United States, erlotinib is currently the only drug available for use in EGFR-positive NSCLC, although elsewhere in the world, another similar drug is widely used: gefitinib (Iressa). A third drug in this class of EGFR tyrosine kinase inhibitors (TKIs), afatanib (Boehringer Ingelheim), is close to approval, with an FDA decision expected in July 2013. Afatanib will also have its own companion diagnostic test ( Therascreen EGFR PCR Kit, from Qiagen).
Using an EGFR TKI in the first-line treatment of EGFR-mutated NSCLC is recommended by several clinical guidelines, including the American Society of Clinical Oncology.
However, testing for mutations is not yet routine, and there are difficulties with obtaining lung cancer samples of sufficient size and quality, as well as disagreement over which is the best method for obtaining such samples, as recently reported by Medscape Medical News. In addition, there are issues with the costs of such testing, as outlined in a comment from a surgeon is response to that article.
The cobas EGFR Mutation Test is manufactured by the Roche Molecular Systems. Erlotinib is co-marketed by California-based Genentech, a member of the Roche Group and OSI Pharmaceuticals.
Absolutely stunning this news that 5 years after treatment using Stereotatic Radiotherapy, 97% of patients with localized Prostate cancer did not have biochemical relapse! That's some result. Can surgery beat that? By how much? Was this a cohort with low Gleason score? will find out!
YES most >92% had Gleason 6 or 7.
IT PAYS TO DISCOVER THE TRUTH!
BUT STILL...STUNNING!
YES most >92% had Gleason 6 or 7.
IT PAYS TO DISCOVER THE TRUTH!
BUT STILL...STUNNING!
CONFLICT OF INTEREST
As a scientist, you tend to believe that your reason will protect against bias. But reason itself is biased by information it gets from so called experts, culture and Media, to just mention a few sources. But when an expert working for a drug company is "pitching" a few key messages to which you are sensitive, somewhere you wonder if the expert opinion is not coerced by someone else's suggestion.
Some of us who have seen the worst cases of Neuropathy induced by Taxanes, have become somewhat "sensitized" to the subject. So to hear that a piano player or artist (who need needs fine hands for their craft) with Metastatic Prostate cancer has to choose between Docetaxel and Abiraterone. To the sensitized oncologist, the choice is clear. Abiraterone is the winner! But was creating a fictitious case of the artist necessary? Or is-it one of the techniques of brain manipulation?
During residency and fellowship, some directors of programs banned lunches from drug companies and avoided drug companies contact with trainees. These decisions are generally unpopular among the trainees who are precluded from free lunches, but are rid of drug companies' influence. As a trainee, I myself had to question the necessity of such exclusive and drastic decision. Ultimately, can we trust a trainee to make up his or her mind? Drug companies on the other hand have their survival in mind and keep sharpening those messages that will influence your practice by any mean they can!
A gardener and writer, spare him the neuropathy! but of course! and the winner is Abiraterone! But know this: soon or later, the Docetaxel conversation is bound to happen! It is the power of the drug and the reliability in providing the cure!
How much confidence do you have by prescribing Abiraterone vs Docetaxel in a patient with metastatic prostate cancer, that you will have a response? and the winner is........ Oncologists, just come on and say it! Let's say in a very symptomatic patient, which drug will you give first? That phase III will not occur in real life!
To mark this fact, researchers did not sleep! It has been reported, at the British Columbia Cancer Agency in Vancouver, they noted that the introduction of Taxotere in the treatment of Hormone Refractory Prostate Cancer has yielded an absolute 6.8% improvement of number of patients alive at 2 years. That's a small town population alive because of the drug! That's the power of a drug (when it hits or follows the law of nature!). Make us believe more and more that the cure is within reach! By the way, that 6.8% was also a 43 % relative improvement in men alive after 2 years! if you don't understand this statistic, well don't kill the messenger ! Just don't you look at ME as a Culprit!
Some of us who have seen the worst cases of Neuropathy induced by Taxanes, have become somewhat "sensitized" to the subject. So to hear that a piano player or artist (who need needs fine hands for their craft) with Metastatic Prostate cancer has to choose between Docetaxel and Abiraterone. To the sensitized oncologist, the choice is clear. Abiraterone is the winner! But was creating a fictitious case of the artist necessary? Or is-it one of the techniques of brain manipulation?
During residency and fellowship, some directors of programs banned lunches from drug companies and avoided drug companies contact with trainees. These decisions are generally unpopular among the trainees who are precluded from free lunches, but are rid of drug companies' influence. As a trainee, I myself had to question the necessity of such exclusive and drastic decision. Ultimately, can we trust a trainee to make up his or her mind? Drug companies on the other hand have their survival in mind and keep sharpening those messages that will influence your practice by any mean they can!
A gardener and writer, spare him the neuropathy! but of course! and the winner is Abiraterone! But know this: soon or later, the Docetaxel conversation is bound to happen! It is the power of the drug and the reliability in providing the cure!
How much confidence do you have by prescribing Abiraterone vs Docetaxel in a patient with metastatic prostate cancer, that you will have a response? and the winner is........ Oncologists, just come on and say it! Let's say in a very symptomatic patient, which drug will you give first? That phase III will not occur in real life!
To mark this fact, researchers did not sleep! It has been reported, at the British Columbia Cancer Agency in Vancouver, they noted that the introduction of Taxotere in the treatment of Hormone Refractory Prostate Cancer has yielded an absolute 6.8% improvement of number of patients alive at 2 years. That's a small town population alive because of the drug! That's the power of a drug (when it hits or follows the law of nature!). Make us believe more and more that the cure is within reach! By the way, that 6.8% was also a 43 % relative improvement in men alive after 2 years! if you don't understand this statistic, well don't kill the messenger ! Just don't you look at ME as a Culprit!
Monday, May 13, 2013
|
|
FOR PERIPHERAL T-CELL LYMPHOMA
FOR PERIPHERAL T-CELL LYMPHOMA
CHOP + ETOPOSIDE = CHOEP
CHOP + CAMPATH(30MG)
CHOP ALONE NO LONGER AN OPTION WITH 2Y SURVIVAL POOR!
ARE SOME OF THE OPTIONS DISCUSSED
CHOP + ETOPOSIDE = CHOEP
CHOP + CAMPATH(30MG)
CHOP ALONE NO LONGER AN OPTION WITH 2Y SURVIVAL POOR!
ARE SOME OF THE OPTIONS DISCUSSED
Ramucirumab
From Wikipedia, the free encyclopedia
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Human |
| Target | VEGFR2 (KDR) |
| Clinical data | |
| Pregnancy cat. | ? |
| Legal status | Investigational |
| Identifiers | |
| CAS number | 947687-13-0  |
| ATC code | None |
| UNII | D99YVK4L0X  |
| Chemical data | |
| Formula | C6374H9864N1692O1996S46 |
| Mol. mass | 143.6 kDa |
 (what is this?) (verify) |
|
Ramucirumab is being tested in several phase III clinical trials for the treatment of breast cancer,[2] metastatic gastric adenocarcinoma,[3] non-small cell lung cancer,[4] among other types of cancer.
This drug was developed by ImClone Systems Inc. It was isolated from a native phage display library from Dyax.
=====================================================
RAMUCIRUMAB IS REPORTED TO HAVE DEMONSTRATED OVERALL SURVIVAL BENEFIT IN SECOND LINE METASTATIC ESOPHAGEAL CANCER 5.2 MONTHS VS 3.8. iT WAS TESTED AGAINST PLACEBO REPORTEDLY! BRAVE PEOPLE! BUT THE RESULT IS NOTICEABLE ! HYPERTENSION, ANEMIA AND FATIGUE WERE THE MOST COMMON SIDE EFFECTS HAPPENING GENERALLY IN IN LESS THAN 10% OF PATIENTS.
============================================================
WE HAVE SO MANY MEDICINE FOR MYELOMA, IT IS TIME TO TREAT THOSE WE HAVE OBSERVED SO FAR. AND HIGH RISK SMOLDERING MYELOMA CAN'T ESCAPE. AT THE EUROPEAN CONGRESS ON HEMATOLOGIC MALIGNANCIES, THE SALVO HAS BEEN SHOT, HIGH RISK MYELOMA HAS BEEN REPORTED TO PROGRESS TO FULL BLOWN MYELOMA IN A MEDIAN TIME OF 2 YEARS OR LESS. SO TREATMENT SEEMS AN ATTRACTIVE OPTION! WITH A MEDIAN SURVIVAL OF 94% vS 85% FOR THOSE OBSERVED AFTER A 47 MONTH FOLLOW-UP! WE ARE WAY INTO TREATING PATIENTS WE USED TO OBSERVE! REV-DEX WAS THE TREATMENT USED!
NO DEED GOES UNPUNISHED, THE STORY OF SECONDARY CANCER, WE JUST HAVE TO BRACE FOR IT!
As we are being increasingly successful at treating cancers, we are being faced with the decision of how long to keep a patient on treatment and maintenance therapy is increasingly pushed. In some surveys, 70 to 80% of oncologists are treating patients "until disease progression" and that could be a year or even several years". The truth is that on a cellular level this is a prolongation of stress and sooner or later something is "gonna break". It is of interest that at the cellular level, that treatment of Hematologic malignancy leads to solid tumors. It goes to show that heterogeneity of genetic material or variation of genes within the same family is exposed to the same stress as imposed by treatments and yields a various effect on a different lineage of cells. Meaning that the suppression of A molecule could affect A2 of the same family, but with a different outcome.
It is clear that prolonged suppression of non intended genes, is the reason for secondary tumors. In some cases, new altered genes are caused by the fragility or susceptibility of the host genome! The point is though, now that we have a secondary cancer with the specific cause, do we look to treat the same as the de-novo cancers? Do we go to the NCCN standard of care, or do we need to aim at the target mutation caused by our previous treatment? Empirically, we suggest that a target therapy would be more efficient, secondary tumors call for a different approach since we have more specific information as to the cause. But a new clinical trial needs to be designed to answer this question!
Secondary tumors happen:
1. When new receptors are completely, irreversibly compromised by our treatment
2. When an related or unrelated gene is is either over-expressed or suppressed (i.e suppression of PTEN) by the treatment.
3. When a bypass activation of collateral gene exists and involves a major pathway (i.e Wnt or Notch pathway by-standing there in the neighborhood!)
4. Some combinations of drugs seem to be prone to causing these secondary tumors (alkylating agents and immunomodulators in myeloma treatment!)
SECONDARY TUMOR IS WAY DIFFERENT FOR DE-NOVO TUMOR! LET'S FACE IT AND BRACE FOR IT!
It is clear that prolonged suppression of non intended genes, is the reason for secondary tumors. In some cases, new altered genes are caused by the fragility or susceptibility of the host genome! The point is though, now that we have a secondary cancer with the specific cause, do we look to treat the same as the de-novo cancers? Do we go to the NCCN standard of care, or do we need to aim at the target mutation caused by our previous treatment? Empirically, we suggest that a target therapy would be more efficient, secondary tumors call for a different approach since we have more specific information as to the cause. But a new clinical trial needs to be designed to answer this question!
Secondary tumors happen:
1. When new receptors are completely, irreversibly compromised by our treatment
2. When an related or unrelated gene is is either over-expressed or suppressed (i.e suppression of PTEN) by the treatment.
3. When a bypass activation of collateral gene exists and involves a major pathway (i.e Wnt or Notch pathway by-standing there in the neighborhood!)
4. Some combinations of drugs seem to be prone to causing these secondary tumors (alkylating agents and immunomodulators in myeloma treatment!)
SECONDARY TUMOR IS WAY DIFFERENT FOR DE-NOVO TUMOR! LET'S FACE IT AND BRACE FOR IT!
NOW THAT IT IS HERE, WE WILL USE IT WHENEVER ABRAXANE IS INVOLVED
ABOUT SPARC LEVEL
Desai et al:
"There were 11 responders (CR/PR) and 5 nonresponders (SD/PD) among the 16 nab-paclitaxel-treated patients (12/16 SPARC-positive, 75%). Response to nab-paclitaxel was higher for SPARC-positive patients (10/12, 83%) than SPARC-negative patients (1/4, 25%). The SPARC-negative patients exhibited significantly lower response than the overall response rate among all 60 patients (1/4, 25% vs 45/60, 75%). Although preliminary, data are supportive of the hypothesis that SPARC overexpression may correlate with response to nab-paclitaxel." This was about Head & Neck cancer, now they are pushing this SPARC level even in Pancreatic cancer without a clinical trial!
Esposito et al
Pancreatic ductal adenocarcinoma (PDAC) and other pancreatic neoplasms exhibited increased SPARCL1 mRNA levels compared to those of the normal pancreas. SPARCL1 mRNA levels were low to absent in microdissected and cultured pancreatic cancer cells, and promoter demethylation increased SPARCL1 levels only slightly in three of eight cell lines. SPARCL1 was observed in small capillaries in areas of inflammation/tumor growth and in some islet cells. In PDAC, 15.4% of vessels were SPARCL1-positive. In contrast, the percentage of SPARCL1-positive vessels was higher in chronic pancreatitis and benign and borderline pancreatic tumors. Recombinant SPARCL1 inhibited pancreatic cancer cell invasion and exerted moderate growth-inhibitory effects. In conclusion, SPARCL1 expression in pancreatic tissues is highly correlated with level of vascularity. Its anti-invasive effects and reduced expression in metastasis indicate tumor-suppressor function."
people are actually testing this sparc1 before giving chemotherapy!
ABOUT SPARC LEVEL
Desai et al:
"There were 11 responders (CR/PR) and 5 nonresponders (SD/PD) among the 16 nab-paclitaxel-treated patients (12/16 SPARC-positive, 75%). Response to nab-paclitaxel was higher for SPARC-positive patients (10/12, 83%) than SPARC-negative patients (1/4, 25%). The SPARC-negative patients exhibited significantly lower response than the overall response rate among all 60 patients (1/4, 25% vs 45/60, 75%). Although preliminary, data are supportive of the hypothesis that SPARC overexpression may correlate with response to nab-paclitaxel." This was about Head & Neck cancer, now they are pushing this SPARC level even in Pancreatic cancer without a clinical trial!
Esposito et al
Pancreatic ductal adenocarcinoma (PDAC) and other pancreatic neoplasms exhibited increased SPARCL1 mRNA levels compared to those of the normal pancreas. SPARCL1 mRNA levels were low to absent in microdissected and cultured pancreatic cancer cells, and promoter demethylation increased SPARCL1 levels only slightly in three of eight cell lines. SPARCL1 was observed in small capillaries in areas of inflammation/tumor growth and in some islet cells. In PDAC, 15.4% of vessels were SPARCL1-positive. In contrast, the percentage of SPARCL1-positive vessels was higher in chronic pancreatitis and benign and borderline pancreatic tumors. Recombinant SPARCL1 inhibited pancreatic cancer cell invasion and exerted moderate growth-inhibitory effects. In conclusion, SPARCL1 expression in pancreatic tissues is highly correlated with level of vascularity. Its anti-invasive effects and reduced expression in metastasis indicate tumor-suppressor function."
people are actually testing this sparc1 before giving chemotherapy!
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