Melanoma

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Synopsis: Health: Illness: Cancer, neoplasms and tumors: Neoplasms and tumors: Melanoma:

#Moffitt researchers discover mechanism leading to drug resistance metastasis in melanoma Moffitt Cancer Center researchers have discovered a mechanism that leads to resistance to targeted therapy in melanoma patients

and a MEK inhibitor being the current standard of care for patients with B-Raf mutant melanoma.

They found that melanoma cells that are resistant to B-Raf inhibitors tend to be more aggressive and invasive,

"said Keiran S. Smalley, Ph d.,scientific director of the Donald A. Adam Comprehensive Melanoma Research center of Excellence at Moffitt.

The research also showed that targeting Epha2 reduced the aggressive behavior of the melanoma cells.

#Melanoma in families linked to mutations in one gene The discovery that mutations in a specific gene are responsible for a hereditary form of melanoma could make it easier to detect and treat,

are extremely likely to develop melanoma, new research shows. These mutations deactivate the POT1 gene. his finding significantly increases our understanding of why some families have a high incidence of melanoma,

says Tim Bishop of the School of medicine at the University of Leeds and a senior co-author of the study published in Nature Genetics. ince this gene has previously been identified as a target for the development of new drugs, in the future,

Known genetic mutations account for approximately 40 percent of all occurrences of inherited forms of melanoma. The team set out to identify the hereditary mutations that account for the other 60 percent by sequencing part of the genome of 184 patients with hereditary melanoma caused by unknown mutations.

They found that the inactivation of POT1 caused by these mutations leads to longer and potentially unprotected telomeres

and brain tumors. ur research is making a real difference to understanding what causes melanoma and ultimately therefore how to prevent

and treat melanoma and is a prime example of how genomics can transform public health, says Julia Newton Bishop,

and patience from the families that suffer from these devastating, inherited forms of melanoma. Cancer Research UK and the Wellcome Trust Sanger Institute funded the work.

targeting HIV, melanoma, and cervical cancer, and tested them in mice. Each one generated a large population of memory T cells specific to the viral

The melanoma vaccine slowed cancer growth and the cervical cancer vaccine shrank tumors. t certainly is an interesting approach,

which is an integration of early diagnosis and treatment of melanoma. Zharov is director of the Arkansas Nanomedicine Center at the UAMS Winthrop P. Rockefeller Cancer Institute and a professor in the UAMS College of Medicine Department of Otolarynology-Head and Neck Surgery.

Zharov has pioneered the development of identifying tumor cellscirculation in the blood stream of melanoma patients by looking directly through the patient veins using a technology called photoacoustic flow cytometry.

and superficial veins and can heat the natural melanin nanoparticles in melanoma circulating tumor cells (CTCS).

we will focus on the most aggressive form of melanoma, which metastasizes at an early disease stage making treatment extremely difficult,

Because not all melanoma cells highly express melanin especially in early disease stages, the researchers proposed genetic,

Zharov said. t will help to better distinguish melanoma-associated small changes in photoacoustic signals at early disease stages.

and melanoma could be the first cancer with metastatic spread that could be treatable by well-timed therapy,

Immune cells with the PD1 biomarker have already been identified as a target for drugs to treat stage-four melanoma

BRAF-mutant melanoma A team of Massachusetts General Hospital (MGH) investigators has discovered a new combination of drugs that may be effective against one of the deadliest cancers, malignant melanoma.

This study utilized 36 well-characterized melanoma cell lines assembled by the MGH Center for Molecular Therapeutics to test all possible combinations of more than 100 oncology drugs,

and cediranib across a broader range of melanoma models, investigate why the particular combination is effective,

and find biomarkers that predict which patients with BRAF-mutant melanoma should receive this combination,

"This study was actually a pilot project for a much larger effort within the Center for Molecular Therapeutics to map responses against drug combinations across hundreds of cancer cell lines, not just melanoma,

#A newly discovered tumor suppressor gene affects melanoma survival Of the hundreds of genes that can be mutated in a single case of melanoma,

a Weizmann Institute of Science team has revealed now one of the drivers of a particularly deadly subset of melanomas-one that is still seeing a rise in new cases.

It is mutated in some 5. 4%of melanomas. Furthermore its expression was found to be lost in over 30%of human melanomas;

and this loss, according to the finding, was associated with reduced patient survival. This discovery might open new doors to understanding how this cancer grows and spreads,

which consists of more than 500 melanoma genomes and exomes-protein-building sequences-making it the largest melanoma dataset to date.

As their name suggests, tumor suppressor genes normally inhibit cell growth, including that of cancer cells.

"The identification of targetable alterations in melanoma is need an urgent. An in depth understanding of the functional effects of mutations in these genes is the first step toward revealing the underlying mechanism of melanoma growth,

"says Dr. Nouar Qutob, a postdoctoral fellow in Samuels'lab who participated in this research. Indeed, the melanoma genome sequences contained mutations in known tumor suppressor genes,

but there was also a new gene that stood out in the team's search, named RASA2.

and the most recurrent mutated versions to see their effects on melanoma cells. They found that RASA2 regulates a key protein in the cell, called RAS.

When they restored the production of the protein in melanoma cells that harbored RASA2 mutations,

Patients with dysfunctional RAS pathways tend to have a worse prognosis than those with other types of melanoma,

to find out what proteins it communicates with in healthy cells and melanoma, as well as in the cells'response to targeted therapy,

"Most targeted cancer therapies nowadays work by inhibiting the products of oncogenes that are overactive in melanoma cells.

However, loss or mutations in tumor suppressor genes like RASA2 also contribute to melanoma development;

#Drug combo shows promise for skin cancer n transitnew melanoma research finds a combination therapy is highly effective at treating patients with skin metastases.

t unclear if the recently developed targeted melanoma therapies that have revolutionized management of patients with internal melanoma metastases are useful in patients with metastatic disease limited of the skin,

Although intralesional IL-2 has recently been included in the US National Comprehensive Cancer Network guidelines for management of melanoma metastases of the skin

About 10 percent of patients with advanced melanoma develop what are called cutaneous metastases, often located n-transitto the patientslymph nodes.

or stage IV melanoma who had history of treatment with IL-2 therapy combined with imiquimod and a topical retinoid.

and seven were alive at the conclusion of the study without melanoma recurrence. The remaining five patients died from unrelated causes. he favorable outcomes in these patients are encouraging

"Based on our clinical data, we helped validate that this could be applied to melanoma and lung cancers,"explained co-author Nhan Tran, Ph d.,associate professor in TGEN's Cancer and Cell biology Division."

and is expressed also in lung cancer and melanoma.""The findings from this study were published recently in Cancer cell through an article entitled argeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein."

such as applying anticancer medications to melanomas or applying growth factors and antibiotics for wound healing, says Jin Di,

#Uncovering Clues About Abnormal Embryo Development with Artificial intelligence Melanoma-like cells in tadpoles may mimic variability in human responses to cancer stimuli.

and metastasis of melanoma-like cells in tadpoles as well as work applying artificial intelligence to help explain planarian regeneration.

and developed other melanoma-like characteristics, proliferating uncontrollably and invading the frogsinternal organs. Depending on which protein in the bioelectric pathway was tweaked, only a certain percentage of the frogs developed melanoma,

while the rest remained healthy. here randomness to this process. It doesn have the same result in all animals exposed to precisely the same agent,

Furthermore, the tadpoles that did develop melanoma developed it in every pigment cellach frog was either 100 percent metastatic or completely normal.

proteins of the serotonergic signaling pathway that regulated the melanoma-like cellsbehavior. Then, the team applied artificial intelligence which mimicked evolution to generate a chemical signaling network in a irtual embryothat exhibited the same behavior that the researchers observed in their experiments with real tadpoles.

the Food and Drug Administration (FDA) announced that it had approved the drug Imlygic to treat late-stage melanoma on the skin and lymph nodes.

Imlygic was tested in more than 400 patients with metastatic melanoma, which kills about 10,000 people per year in the United states,

"Based on our clinical data, we helped validate that this could be applied to melanoma and lung cancers,"said Dr. Nhan Tran, an Associate professor in Translational Genomics Research Institute (TGEN)' s Cancer and Cell biology Division,

and is expressed also in lung cancer and in melanoma.""Malaria uses VAR2CSA to embed itself in the placenta--hiding itself from the immune system--by binding to oncofetal chondroitin sulfate.

The discovery point towards the possibility of identifying aggressive melanomas at an earlier stage than is currently possible,

Pigment Cell & Melanoma Research. May be possible to predict disease progression It is the first time that the protein megalin,

and relapse or not from a malignant melanoma.""It is a new and interesting marker that no one has thought of before.

Even though we currently see considerable progress and success from novel treatment strategies for patients with metastatic melanoma,

#Immunotherapy combination promising for untreated patients with advanced melanoma The combination of two immunotherapies for first-line treatment of advanced melanoma induces better responses

Further, the combination was effective in the portion of melanoma patients--the majority--who currently have few effective treatment options. hase 2 clinical trial led by Ludwig Harvard's Stephen Hodi

and Ludwig Memorial Sloan Kettering (MSK)' s Jedd Wolchok has found that the combination of two immunotherapies for first-line treatment of advanced melanoma induces better responses

the combination was effective in the portion of melanoma patients--the majority--who currently have few effective treatment options.

who is also director of the Melanoma Center at the Dana-Farber Cancer Institute.""It's very encouraging to see that pattern reflected in this trial with previously untreated patients."

and is also the Chief of the Melanoma and Immunotherapeutics Service at MSK, found that the same concurrent combination of therapies generated notably positive responses in previously treated patients."

"It was apparent following that trial that the combination should be tested as a first line therapy for metastatic melanoma,

The Phase 2, double-blind trial enrolled 142 patients with advanced melanoma who had received not prior therapy.

which is mutated frequently in melanoma. This is significant because while melanoma patients with the mutant BRAF gene can be treated with a targeted therapy, the majority

whose tumors encode a normal BRAF have few effective treatment options. In this group of patients, 72 received ipilimumab plus nivolumab, followed by nivolumab alone,

The researchers validated this finding in advanced melanoma patients, who have increased TGF? plasma levels and higher levels of Id1 in myeloid peripheral blood cells.

a multifunctional protein involved in melanoma development and progression, in the cellular response to UV radiations.

our findings will likely help to shed light on the molecular mechanisms of tumorigenesis, especially in tumour types like melanoma, in which exposure to UV radiations plays such a prominent part.

The comparison involved the normal and tumor genomes from 43 children and adults with brain tumors, leukemia, melanoma and the pediatric eye tumor retinoblastoma."

Since 2010, the FDA has approved vaccines and other immunotherapy drugs for melanoma, prostate cancer, and lung cancer.

The finding was confirmed in samples from patients receiving high-dose interleukin 2 therapy to treat metastatic melanoma."

which means that melanoma is identified in all cases where it is ruled present, and out in 90.9%of cases where it is not."

Combined drug regimens designed to overcome drug resistance at the outset of therapy are now the norm in treating certain forms of melanoma,

At the same time, the discovery also opens new doors for future improved treatment of patients with melanomas.

Melanoma metastases are furthermore extremely difficult to eliminate as traditional treatment such as chemotherapy and radiotherapy is mostly ineffective.

The discovery point towards the possibility of identifying aggressive melanomas at an earlier stage than is currently possible,

Pigment Cell & Melanoma Research. May be Possible to Predict Disease Progression It is the first time that the protein megalin,

Even though we currently see considerable progress and success from novel treatment strategies for patients with metastatic melanoma,

Lam and his fellow researchers followed up this observation by looking at different types of cancers with known pain associations for instance, certain breast and melanoma cell lines.

while melanoma, or skin cancer, sits at the bottom of the pain scale. But what surprised the researchers was that the presence

and skin cancer, known as melanoma. More than 22,000 new cases of brain cancer and more than 73,000 new cases of skin cancer and were expected to arise in Americans in 2015, according to the National Cancer Institute.

which means that melanoma is identified in all cases where it is ruled present, and out in 90.9%of cases where it is not. rofessor Marco Rossi of Pisa University said:

such as applying anticancer medications to melanomas or applying growth factors and antibiotics for wound healing, said Jin Di,

Surprisingly the loss of STAT3 in NK cells of the mouse led not to a decrease but to an increase in killing activity against melanoma cells and leukemia cells.

The decrease in metastasis caused by melanoma cells was especially dramatic and confirmed that NK cells lacking STAT3 are extremely efficient killers of tumour cells.

what is seen in melanoma cells s

#Experimental rapid test could tell sinusitis sufferers if they need antibiotics...or just patience It's that time of the year where a perfect storm of fall allergies

has defined a subgroup of genetic mutations that are present in a significant number of melanoma skin cancer cases.

The role of mutations in numerous genes and genomic changes in the development of melanoma a skin cancer with over 70

Yet in approximately 30%of melanoma cases the genetic abnormalities are unclear. To deepen understanding of melanoma mutations,

the Yale team conducted a comprehensive analysis using whole-exome sequencing of more than 200 melanoma samples from patients with the disease.

The multidisciplinary team drawing on their expertise in genetics, cancer, computational biology, pharmacology, and other disciplines also tested the response of tumor cells with specific mutations to anticancer drugs.

The researchers confirmed that a gene known as NF1 is a ajor playerin the development of skin cancer. he key finding is that roughly 45%of melanomas that do not harbor the known BRAF or NRAS mutations display loss of NF1 function,

Additionally, researchers observed that melanoma patients with the NF1 mutation were had older and a greater number of mutations in the tumors.

By testing the response of the melanoma samples to two cancer drugs, the researchers also determined that,

the Melanoma Research Alliance; Gilead sciences, Inc.;the Howard Hughes Medical Institute; the Department of Dermatology;

Michael Krauthammer, et al, xome sequencing identifies recurrent mutations in NF1 and RASOPATHY genes in sun-exposed melanomas, Nature Genetics, 2015;

Specialists at the NHS Royal Marsden Hospital and the Institute of Cancer Research (ICR) confirmed that melanoma skin cancer patients treated with a modified herpes virus (the virus that causes cold sores) had improved survival-a world first.

Melanoma is the fifth most common cancer in the UK, and is becoming more widespread

and 2, 000 people still die from melanoma in the UK every year. Scientists have the first proof that a"brand new"way of combating cancer,

Specialists at the NHS Royal Marsden Hospital and the Institute of Cancer Research (ICR) confirmed that melanoma skin cancer patients treated with a modified herpes virus (the virus that causes cold sores) had improved survival-a world first.

Melanoma is the fifth most common cancer in the UK, and is becoming more widespread

and 2, 000 people still die from melanoma in the UK every year r

#Cells that aid hearing, balance created in lab LONDON: Scientists have developed successfully a way to coax embryonic stem cells to become the inner-ear hair cells

stretchy electronic sensors are also capable of detecting harmful levels of UV radiation known to trigger melanoma.

melanoma and ovarian cancer. By shutting down the epithelialesenchymal transition process, Zink and Tamanoi may develop new therapy options for these cancers.

"My Phd supervisor, she found her melanoma when she was designing the device, just testing the image quality,"said Sadeghi."

and melanoma cancers. The researchers observed CTC clusters ranging from 2-19 cells among 300%of the patients."

31%of prostate and 30%of melanoma patientsuggestive of a greater role for CTC clusters in metastatic cancers than previously thought.

Patients with stage III and early stage IV melanoma a condition that was shown to carry an average survival of 21.5 months

The scientists say that T-VEC is the first of such viral therapies to be proven beneficial in treating melanoma in a phase III clinical trial.

and melanoma cancers. The researchers found CTC clusters--ranging from two to 19 cells--in 30-40 percent of the patients."

including those that lose surface proteins during metastasis and those that never express them, such as melanoma.

In this study, the chip captured CTC clusters in 11 of 27 (40.7 percent) breast cancer patients, 6 of 20 (30 percent) melanoma patients

"The team tested the therapeutic potential of the nanoparticles by loading them with an anti-melanoma drug

In further experiments, the researchers found they could alter the infusion of the particles into melanoma cells by adjusting the polymer coatings.

"This is a versatile platform to carry a multitude of drugs-for melanoma, for other kinds of cancers and for other diseases,

stretchy electronic sensors are also capable of detecting harmful levels of UV radiation known to trigger melanoma.

durable benefit for people with melanoma, said Dr Harrington. Professor Paul Workman, Chief executive of the ICR, said in a statement,

which is known to trigger melanoma (a type of skin cancer that can develop from abnormal moles).

The results come from a clinical trial in the UK involving more than 400 patients with aggressive melanoma,

According to the study, published in The Journal of Clinical Oncology, of the 436 patients with inoperable melanoma, 16.3 percent of them were still in remission six months after the treatment,

"They had ranged disease that from dozens to hundreds of deposits of melanoma on a limb all the way to patients where cancer had spread to the lungs and liver,

and found that melanoma responded the most positively to it. The team figured out how to harness its amazing capacity for replication by removing two genes that made it impossible for it to multiply inside healthy cells,

but it still had its run of things inside the cancerous melanoma cells.""Meanwhile, T-VEC has also been modified to produce a molecule called GM-CSF,

and early trials show that they may also be far more effective-with studies so far proving immunotherapy is successful against aggressive forms of melanoma and glioblastoma.

"This is a versatile platform to carry a multitude of drugs-for melanoma, for other kinds of cancers and for other diseases,"says Rohit Bhargava."

#Mechanism leading to drug resistance metastasis in melanoma patients discovered Moffitt Cancer Center researchers have discovered a mechanism that leads to resistance to targeted therapy in melanoma patients

and a MEK inhibitor being the current standard of care for patients with B-Raf mutant melanoma.

They found that melanoma cells that are resistant to B-Raf inhibitors tend to be more aggressive and invasive,

"said Keiran S. Smalley, Ph d.,scientific director of the Donald A. Adam Comprehensive Melanoma Research center of Excellence at Moffitt.

The research also showed that targeting Epha2 reduced the aggressive behavior of the melanoma cells.

#Key factor discovered in formation of metastases in melanoma Melanoma, the most aggressive of all skin cancer strains, is often fatal for patients due to the pronounced formation of metastases.

Until now, a melanoma's rampant growth was attributed mainly to genetic causes, such as mutations in certain genes.

malignant metastatic formation of melanoma, was previously put down to the high mutation rate that is characteristic of melanoma,

whether epigenetic factors are especially active in melanoma cells --and stumbled across EZH2, an epigenetic control protein found very frequently in malignant melanoma cells compared to normal cells.

"Sommer's team was able to demonstrate that, in melanoma cells, the epigenetic factor EZH2 controls genes that govern tumor growth as well as genes that are important for the formation of metastases.

As a result, the researchers were able to prevent the growth and malignant spread of the cancer in the animal model and human melanoma cells."

including melanoma, lung cancer, and breast cancer. It belongs to a group of proteins known as"cancer/testis antigens,

whose lab focus includes non-melanoma skin cancer, in which GLUT1 is expressed highly d

#First live birth after transplantation of ovarian tissue removed and frozen during childhood Arraythe patient, who was born in the Republic of congo,

called AIM2 (Absent in Melanoma 2), plays a role in determining the aggressiveness of colon cancer.

or Absent in Melanoma 2, helps prevent colon cancer by restricting a signaling molecule called Akt.

#Activated T cell therapy for advanced melanoma developed Published in the July/August issue of Journal of Immunotherapy,

these new findings demonstrate that T cells derived from lymph nodes of patients with melanoma can be expanded in number

which have been exposed to growing melanoma in the patient's body. Rather than trying to activate the T cells while in the body,

These promising findings have led to the recent launch of a new Phase I human clinical trial at UH Seidman Cancer Center in patients with advanced melanoma.

In 2008, Dr. Prat team identified a cell adhesion molecule, called MCAM (Melanoma Cell adhesion molecule), which plays a crucial role in dysregulation of the immune system observed in multiple sclerosis. ur studies have shown that MCAM is necessary for the migration of CD4 and CD8 across the blood-brain barrier.

IVM1A) and those who had yet to receive any treatment underlining the potential benefits of T-VEC as a first-line treatment for metastatic melanoma

Patients with stage III and early stage IV melanoma treated with T-VEC a total of 163 people lived an average of 41 months.

or some of the other new immunotherapies. ur study showed that T-VEC can deliver a significant, durable benefit for people with melanoma.

if it can become a first-line treatment for more aggressive melanomas and advanced disease. rofessor Paul Workman,

and a team of international scientists found that stage IIIB to IV melanoma patients treated with a modified cold sore (herpes virus had improved survival.

or metastatic, melanoma. Before entering the T-VEC trial, she had been through numerous procedures and major surgeries.

The U s. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) are considering findings from the trial to make the treatments available to more patients with advanced melanoma.

The article describes an immunotherapy for melanoma utilizing the checkpoint inhibitors, ipilimumab and nivolumab. In cell biology

The study found that injection of the two inhibitors shrunk tumors in the majority of patients with advanced melanoma.

Chesney said. believe T-VEC combined with immune checkpoint inhibitors will not only reduce cancer-related mortality in melanoma but in all cancer types,

The team of researchers tested the therapeutic potential of these carbon nanoparticles by loading them with an anti-melanoma drug

Scientists also found that they can alter the infusion of the particles into melanoma cells by adjusting the polymer coatings.

It is a very versatile platform to treat melanoma, other kinds of cancers and other diseases.

melanoma or prostate cancer successfully captured CTC clusters in from 30 to 40 percent of samples from each group.

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