Immunotherapy and Chemotherapy Regimen May Prolong Survival in Advanced Cancers

In continuation of my update on interleukin and retinoic acid

Cancer patients who receive a combination of low-dose interleukin-2 and retinoic acid after conventional therapy seem to live longer than those who don't get the combination. 

Retinoic acid is derived from vitamin A. Interleukin-2, a compound that fortifies the immune system, is approved at high doses to treat "metastatic" melanoma and kidney cancer. Metastatic means that a cancer has spread.

The study showed that "these biological compounds may work at low doses. Bigger doses are not always better," said lead author Dr. Francesco Recchia, director of the oncology department at Civilian Hospital in Avezzano, Italy.

Recchia stumbled upon the possibility of using low-dose interleukin-2 (IL-2) when he switched a patient with metastatic melanoma who didn't tolerate high doses to a lower dose, and the patient had an extended response to the therapy.

This study involved 500 patients who had already responded well to chemotherapy. They had a variety of cancers, including ovarian, lung, colon, stomach, kidney, melanoma, breast and pancreatic.

Immunotherapy and Chemotherapy Regimen May Prolong Survival in Advanced Cancers

Apremilast a new hope for severe Psoriasis...

About apremilast :

(S)-N-{2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methanesulfonyl- ethyl]- 1,3-dioxo - 2,3 -dihydro - 1H-isoindol-4-yl}acetamide.

Apremilast, is a member of a proprietary pipeline of novel small molecules with anti-inflammatory activities that inhibit the production of multiple proinflammatory mediators including, PDE-4, TNF-alpha, interleukin-2 (IL-2), interferon-gamma, leukotrienes, and nitric oxide synthase.

Now Celgene announces positive data from its apremilast Phase IIb study for plaque-type psoriasis.

As per the claim by the company, 41% of patients treated with 30mg of oral apremilast BID achieved a PASI-75 after 16 weeks (p<0.001).

Ref : :http://ir.celgene.com/phoenix.zhtml?c=111960&p=irol-newsArticle&ID=1365878&highlight=

Potential drug for treatement of Alzheimer's disease investigated

Cannabinoid type 2 (CB₂) agonists are neuroprotective and appear to play modulatory roles in neurodegenerative processes in Alzheimer's disease. We have studied the effect of 1-((3-benzyl-3-methyl-2,3-dihydro-1-benzofuran-6-yl) carbonyl) piperidine (MDA7 see below structure), a novel selective CB₂ agonist that lacks psychoactivity—on ameliorating the neuroinflammatory process, synaptic dysfunction, and cognitive impairment induced by bilateral microinjection of amyloid-β (Aβ)_1–40 fibrils into the hippocampal CA1 area of rats. In rats injected with Aβ_1–40 fibrils, compared with the administration of intraperitoneal saline for 14 days, treatment with 15 mg/kg of intraperitoneal MDA7 daily for 14 days (1) ameliorated the expression of CD11b (microglia marker) and glial fibrillary acidic protein (astrocyte marker), (2) decreased the secretion of interleukin-1β, (3) decreased the upsurge of CB₂ receptors, (4) promoted Aβ clearance, and (5) restored synaptic plasticity, cognition, and memory. Our findings suggest that MDA7 is an innovative therapeutic approach for the treatment of Alzheimer's disease.

Potential drug for treatement of Alzheimer's disease investigated

Anticancer & Antiinflammatory properties of Lunasin (Soy Peptide) established ?...

We know that many researchers have tried to establish the anticancer activity of the peptide lunasin (which has been already accepted as neutraceutical agent). Now researchers from University of Illinois have come up with more interesting facts, Soy peptide often discarded in the waste streams of soy-processing plants, may have important health benefits that include fighting leukemia and blocking the inflammation that accompanies such chronic health conditions as diabetes, heart disease, and stroke.

The researchers confirmed lunasin's bioavailability in the human body by doing a third study in which men consumed 50 grams of soy protein--one soy milk shake and a serving of soy chili daily-for five days. Significant levels of the peptide in the participants' blood give us confidence that lunasin-rich soy foods can be important in providing these health benefits.

In the cancer study, de Mejia's group identified a key sequence of amino acids- arginine, glycine, and aspartic acid, (the RGD motif)--that triggered the death of leukemia cells by activating a protein called caspase-3. The scientists also verified lunasin's ability to inhibit topoisomerase 2, an enzyme that marks the development of cancer, and they were able to quantify the number of leukemia cells that were killed after treatment with lunasin in laboratory experiments.

More interesting out come of their study is lunasin's potential anti-inflammatory activity, (first time) they showed that lunasin blocked or reduced the activation of an important marker called NF-kappa-B, a link in the chain of biochemical events that cause inflammation. They also found statistically significant reductions in interleukin-1 and interleukin-6, both important players in the inflammatory process (the reduction in interleukin-6 was particularly strong). As per the claim by the group, although the high cost of obtaining lunasin from soy waste limits its use for nutritional interventions, soy flour does contain high concentrations of the peptide (depending on some genotype soy).

Its good see the diverse activities associated with Soy......

Source : http://pubs.acs.org/doi/abs/10.1021/jf803303k?prevSearch=Elvira%2Bde%2BMejia&searchHistoryKey=

Baricitinib Exhibits Steroid-Sparing Effect in PMR Trial

In coninuation of my update on Baricitinib

Baricitinib had a significant glucocorticoid (GC)-sparing effect in people with newly diagnosed polymyalgia rheumatica (PMR), who participated in the phase 3 JAK-Spare trial, was according to results reported at the European Alliance of Associations for Rheumatology (EULAR) 2026 Annual Meeting.

GC-free remission at week 16 was achieved in nearly two thirds (65.2%) of the 23 people who had received the drug in the trial, as compared to 17.4% of the 23 people who had been treated with placebo (P < .01).

And when participants who had initially been treated with placebo crossed over to treatment with baricitinib, their GC-free remission rate at week 28 increased to 65.2%. The GC-free remission rate in the baricitinib arm also increased to 78.3%.

Study investigator Helga Lechner-Radner, MD, of the Medical University of Vienna in Vienna, Austria, reported the trial’s findings during the late-breaking abstract session. She told Medscape Medical News that the findings were “important because we do still have a lot of patients on steroids, because whenever we try to reduce or taper steroids, they relapse again.”

Baricitinib is a drug that is “efficacious and safe in many of our [rheumatic and musculoskeletal] diseases. We know the mechanism, we know the safety profile, and therefore, it also makes sense to also test this drug in this patient population,” Lechner-Radner added.

The JAK-Spare Study

The JAK-Spare study involved 46 people with recently diagnosed PMR who were recruited between July 2022 and May 2024 across five European centers. The mean age of the recruited participants was 65 years, just over half were men, and all were White.

Crucially, a very early diagnosis (within 3 weeks) was needed for inclusion so that participants had not been taking GCs for very long, Lechner-Radner said. The average disease duration before enrollment was just 16 days, and the average daily oral GC dose was 18 mg.

Participants were randomly allocated to receive baricitinib 4 mg/d or to a placebo. A rapid GC-tapering regimen was used in both arms, which aimed to reduce the dose of GCs to zero within 11 weeks rather than the usual 52 weeks. After the initial 16-week study period, patients in the placebo group crossed over to treatment with baricitinib, while those in the baricitinib arm continued treatment. Then at 28 weeks, participants in GC-free remission were randomly assigned again either to continue baricitinib 4 mg/d through week 44 or lower their dose of baricitinib to 2 mg/d, stopping it altogether from 36 to 44 weeks.

Lechner-Radner said in an interview that GCs were given from the outset in the trial in both treatment arms because the investigators felt that it would not have been ethical to give patients newly diagnosed with PMR no treatment at all.

This is in contrast to the BACHELOR trial in which baricitinib was compared against no treatment initially in the placebo arm, with intravenous (IV) and oral GCs used only as a rescue treatment from week 4 onward. However, IV GCs are not licensed for this purpose in Austria, she said, and “they have a high dropout rate because many of those patients needed to be rescued.”

Lechner-Radner also said that, as an oral tablet, baricitinib is “an easy medication [to take]” when compared to those that require injection.

Reductions in GC Use

Assessment at week 28 showed continued improvement in the baricitinib arm, with 78.3% of participants in GC-free remission, but 65.2% of those originally in the placebo group were also now in GC-free remission, up from 17.4% at 16 weeks.

The time to relapse was significantly longer with baricitinib than placebo (P = .008). Participants in the baricitinib arm also took a lower median cumulative GC dose than those in the placebo group, at 736 mg vs 1065 mg at 16 weeks (P = .015) and 736 mg vs 1086 mg at 28 weeks (P = .013).

After re-randomization of the 33 patients who were in GC-free remission at 28 weeks, GC-free remission continued out to 44 weeks in 93.3% of those still taking baricitinib 4 mg/d and in 72.2% of those who tapered to 2 mg/d and then 0 mg/d (P = .186). Flare-free survival was higher among people who continued to take baricitinib 4 mg/d but was not statistically significant from those who tapered and then stopped baricitinib.

In each phase of the study, the percentages of participants with at least one adverse event were similar between the groups, at 87% in both in the first phase, 60.9% with baricitinib 4 mg/d vs 43.5% in the placebo crossover in the second phase, and 80% with baricitinib 4 mg/d vs 66.7% in those who tapered baricitinib in the third phase.

New Steroid-Sparing Option in PMR?

“With PMR, one wants to get patients off steroids as quickly as possible. Steroid therapy is quite toxic, and this is minimized by short duration of use and at a low dose,” Jonathan Kay, MD, professor of medicine and population and quantitative health sciences and the Timothy S. and Elaine L. Peterson Chair in Rheumatology at the UMass Chan Medical School in Worcester, Massachusetts, told Medscape Medical News. He was not involved in the trial.

But “if you can get someone on a medication that has less likelihood of causing toxicity than the steroid, the better that is going to be for the patient,” he added.

While these were positive data for a JAK inhibitor, Kay wondered whether such a drug would be likely to gain approval for use in this indication from regulatory authorities.

“In the United States, JAK inhibitors are restricted to patients who failed TNF [tumor necrosis factor] inhibitors,” he explained. “So will the FDA allow the label change to allow JAK inhibitors to be used in PMR before TNF inhibition?”

Kay pointed out that the interleukin 6 inhibitor sarilumab, which is given by subcutaneous injection every 2 weeks, is already approved to treat PMR.

https://en.wikipedia.org/wiki/Baricitinib

Baricitinib Exhibits Steroid-Sparing Effect in PMR Trial

Icotrokinra Beneficial for Adults, Teens With Plaque Psoriasis

For adults and adolescents with moderate-to-severe plaque psoriasis, selective blockade of the interleukin-23 receptor with the targeted oral peptide icotrokinra yields a significantly higher incidence of skin clearance at week 16 than placebo, according to a study published in the Nov. 6 issue of the New England Journal of Medicine.

Robert Bissonnette, M.D., from Innovaderm Research in Montreal, and colleagues conducted a phase 3, randomized trial involving adults and adolescents (aged 12 years and older) with moderate-to-severe plaque psoriasis. Participants were randomly assigned to receive either icotrokinra (200 mg once daily through week 24) or placebo through week 16 followed by transition to icotrokinra (456 and 228 patients, respectively).

The researchers found that 65 percent of the participants receiving icotrokinra and 8 percent of those receiving placebo had an Investigator's Global Assessment (IGA) score of 0 or 1 with ≥2-point reduction from baseline at week 16, and 50 and 4 percent, respectively, had a ≥90 percent reduction from baseline in the Psoriasis Area and Severity Index (PASI) score. At week 16, complete clearance of skin was significantly more likely with icotrokinra than placebo (IGA score 0: 33 versus 1 percent; 100 percent reduction from baseline in the PASI score: 27 versus 1 percent). In each group, 49 percent of patients had at least one adverse event through week 16.

"Once-daily icotrokinra, a systemic targeted oral peptide binding to the interleukin-23 receptor, was effective for treating plaque psoriasis in adults and in adolescents, an age group with limited systemic treatment options," the authors write.

https://en.wikipedia.org/wiki/Icotrokinra

Icotrokinra Beneficial for Adults, Teens With Plaque Psoriasis - Drugs.com MedNews

Researchers able to predict and reverse resistance to Sunitinib treatment....

Van Andel Research Institute (VARI) researchers have found a way to  reverse resistance to Sunitinib (see structure), a treatment that is currently the first line of defense against clear cell renal cell carcinoma (ccRCC), a deadly form of kidney cancer. Most patients who show a positive response to Sunitinib develop a resistance to the drug after one year of treatment.

Researchers lead by Dr. Teh, Bin Tean found that ccRCC tumor cells that had developed a resistance to Sunitinib had increased secretion of the protein interleukin-8 (IL-8). Administering Sunitinib and IL-8 neutralizing antibodies re-sensitized tumors to sunitinib treatment. Researchers also found that IL-8 may serve as a useful biomarker to predict patients' response to sunitinib treatment.

Interestingly,  another  study from same  group  of  Teh’s laboratory, looked into exactly how sunitinib works.  The study found that the treatment does not target tumor cells, but rather the tumor’s blood supply.

Researchers conclude that “it is now of critical importance to validate these findings in the clinical setting" and they hope that these insights will help to build upon recent advances to extend clinical benefits to more patients with metastatic kidney cancer....

Ref : 1.  Cancer Research 70, 1053, February 1, 2010. 

        2.  Cancer Research 70, 1063, February 1, 2010