UP TO DATE INFORMATION AND NEWS RELATED TO CANCER RESEARCH AND TREATMENT FOR CANCER PATIENTS AND COMMUNITY.
TRANSLATE
Wednesday, 30 May 2018
The viruses that are most likely to cause cancer in people with HIV are:
- Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), which causes Kaposi sarcoma and some subtypes of lymphoma
- Epstein-Barr virus (EBV), which causes some subtypes of non-Hodgkin and Hodgkin lymphoma
- Human papillomaviruses (HPV), high-risk types of which cause cervical cancer, most anal cancers, and oropharyngeal, penile, vaginal, and vulvar cancer
- Hepatitis B virus (HBV) and hepatitis C virus (HCV), which both cause liver cancer
Monday, 28 May 2018
Thursday, 24 May 2018
Tumor Agnostic Immune Checkpoint Inhibitors
Exploring a new era of cancer research at this year’s ASCO event
I am proud to share my last blog for the ASCO 2018 done toguether with Dr Forrest Antony supported by IQVIA. ASCO is the biggest medical congress in cancer which is attended by 30.000+ oncologists all over the world.
https://www.iqvia.com/blogs/2018/05/tumor-agnostic-immune-checkpoint-inhibitorsMonday, 21 May 2018
Tuesday, 15 May 2018
Thyroid nodules are common but usually are not cancer
Your doctor may find a lump (nodule)
in your thyroid during a routine medical exam. A thyroid nodule is an abnormal
growth of thyroid cells
in the thyroid. Nodules may be solid or fluid
-filled.
When a thyroid nodule is found, an ultrasound
of the thyroid and a fine-needle aspiration biopsy are often done to check for signs
of cancer.
Blood tests
to check thyroid hormone levels and for antithyroid antibodies
in the blood
may also be done to check for other types of thyroid disease.
Thyroid nodules usually don't cause symptoms
or need treatment. Sometimes the thyroid nodules become large enough that it is
hard to swallow or breathe and more tests and treatment are needed.
Only a small number of thyroid nodules are diagnosed as cancer.
Thyroid cancer may not cause early signs or symptoms. It
is sometimes found during a routine physical exam.
Signs or symptoms may occur as the tumor
gets bigger. Other conditions may cause the same signs or symptoms. Check with
your doctor if you have any of the following:
A lump (nodule) in the neck, trouble breathing, trouble
swallowing, pain when swallowing and hoarseness.
Monday, 7 May 2018
Venetoclax Shows Promise as Salvage Therapy in CLL
Venetoclax (Venclexta) induced a response in two-thirds of
patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who had
progressed after receiving prior therapy with idelalisib (Zydelig), according
to findings of a phase II study recently published in Blood.
Venetoclax was associated with a 67% investigator-assessed overall response rate (ORR) among patients who had received prior idelalisib (n = 36).
Venetoclax was associated with a 67% investigator-assessed overall response rate (ORR) among patients who had received prior idelalisib (n = 36).
FDA granted a Fast Track Designation for a new drug in Multiple Myeloma
Selinexor (KPT-330) was recently granted a Fast Track
designation by the FDA for the treatment of patients with multiple myeloma who
have received at least 3 prior lines of therapy, according to Karyopharm
Therapeutics, the manufacturer of the oral SINE (selective inhibitor of nuclear
export) compound.
Selinexor links to and inhibits XPO1, a nuclear export protein, which leads to the accumulation of tumor suppressor proteins in the nucleus of the cell. This reinitiates and amplifies their tumor suppressor function, which investigators believe leads to the selective induction of apoptosis in cancer cells, while sparing normal cells.
The designation is based on data from the phase IIb STORM study, a single-arm, open-label, multicenter study of selinexor plus dexamethasone in patients with penta-refractory multiple myeloma.
Selinexor links to and inhibits XPO1, a nuclear export protein, which leads to the accumulation of tumor suppressor proteins in the nucleus of the cell. This reinitiates and amplifies their tumor suppressor function, which investigators believe leads to the selective induction of apoptosis in cancer cells, while sparing normal cells.
The designation is based on data from the phase IIb STORM study, a single-arm, open-label, multicenter study of selinexor plus dexamethasone in patients with penta-refractory multiple myeloma.
Friday, 4 May 2018
Thursday, 3 May 2018
A Potential Anticancer Drug From Poppies Has Been Produced in Genetically Engineered Yeast
Researchers
from Stanford University and collaborating institutions have successfully
synthesized noscapine, a potential anticancer drug, in yeast cells. Noscapine,
a nonnarcotic cough suppressant that is also being investigated as a potential
anticancer drug, currently has only one source—the opium poppy. Because
environmental factors such as pests, disease, and climate can threaten the
poppy crop, which is only grown in a limited geographic area, other ways of
producing noscapine are needed to ensure a stable supply of the drug.![Image result for poppies](data:image/jpeg;base64,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)
The research
team developed a strain of the yeast Saccharomyces cerevisiae that can
produce noscapine from simple carbon and nitrogen sources through a biochemical
pathway that involves 31 enzymes taken from a variety of sources including
plants, mammals, and bacteria. They then used multiple techniques to optimize
noscapine production, leading to an 18,000-fold improvement in the amount
produced. They also used their engineered yeast strain to produce novel
compounds related to noscapine, some of which might also be able to be
developed into drugs.
This work
demonstrates the potential for microorganisms such as yeast to serve as
platforms for complex syntheses of valuable natural products from simple
chemical building blocks. Microbial synthesis can ensure a reliable supply of a
product and can provide greater batch-to-batch consistency in product
composition than can be achieved with plants. Also, the desired compounds can
be produced far more quickly; it takes only days to cultivate the yeast used to
produce noscapine, but it takes an entire growing season to raise a crop of
opium poppies. The success of this project, in combination with previous drug on
drug synthesis in genetically engineered yeasts, highlights the transformative
effect that synthetic biology may have on the development and production of
drugs and other complex plant-derived chemicals.
Reference
- Li Y, Li S, Thodey K, et al. Complete biosynthesis of noscapine and halogenated alkaloids in yeast. Proceedings of the National Academy of Sciences. April 2, 2018. [Epub ahead of print].
Wednesday, 2 May 2018
FDA approves new indication for CAR T-cell therapy to be use in adults with relapsed/refractory Large B-Cell lymphoma
The FDA has approved tisagenlecleucel – CART T-cell
therapy- (Kymriah) for use in adult patients with relapsed/refractory large
B-cell lymphoma—including diffuse large B-cell lymphoma (DLBCL), high-grade
B-cell lymphoma and DLBCL arising from follicular lymphoma—after 2 or more
lines of systemic therapy.
The approval is based on the phase II JULIET study, in which the CD19-directed chimeric antigen receptor (CAR) T-cell therapy reached an overall response rate (ORR) of 50% (95% CI, 38%-62%) in adult patients with relapsed/refractory DLBCL. The complete response (CR) rate was 32% and the partial response rate was 18%. The median duration of response had not been reached.
The approval is based on the phase II JULIET study, in which the CD19-directed chimeric antigen receptor (CAR) T-cell therapy reached an overall response rate (ORR) of 50% (95% CI, 38%-62%) in adult patients with relapsed/refractory DLBCL. The complete response (CR) rate was 32% and the partial response rate was 18%. The median duration of response had not been reached.
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