- A safety profile of medications used to treat Waldenström's macroglobulinemia. [Journal Article]
- EOExpert Opin Drug Saf 2018 May 17
- Waldenström's macroglobulinemia (WM) is a B-cell lymphoproliferative disease with serum IgM monoclonal component and bone marrow infiltration by lymphoplasmacytic lymphoma. Traditional therapy was ba...
Waldenström's macroglobulinemia (WM) is a B-cell lymphoproliferative disease with serum IgM monoclonal component and bone marrow infiltration by lymphoplasmacytic lymphoma. Traditional therapy was based on that regimens used for closely related entities, such as chronic lymphocytic leukemia or multiple myeloma. This resulted in a lack of drugs specifically approved for WM, until the discovery of the BTK inhibitors. Areas covered. Two main therapeutic attitudes are possible: 1) conventional therapies based on combinations with alkylating agents or proteasome inhibitors with steroids and anti-CD20 monoclonal antibodies, or; 2) new approaches with BTK inhibitors, usually alone. Other possibilities such as BCL2 inhibitors, PI3K/AKT inhibitors, and others are currently under evaluation, but we will focus the review on the most consolidated approaches that are available for patients with WM at different stages of the disease. PubMed, Web of Science, and clinicaltrials.gov were queried for the keywords "Waldenstrom macroglobulinemia" and the different drugs here evaluated through February 1, 2018. Expert opinion: although WM has no many specific drugs, there are many possible therapies, including Ibrutinib, the first formally approved drug for this disorder.
- A look at treatment strategies for relapsed multiple myeloma. [Journal Article]
- ERExpert Rev Anticancer Ther 2018 May 16
- Multiple myeloma treatment considerably improved during the past decade, thanks to novel effective drugs, a better understanding of myeloma biology and clonal heterogeneity, and an improved managemen...
Multiple myeloma treatment considerably improved during the past decade, thanks to novel effective drugs, a better understanding of myeloma biology and clonal heterogeneity, and an improved management of toxicities. The choice of regimen at relapse is usually based on prior response, toxicities, age and comorbidities of relapsed patients. Areas covered: A review was performed of the most recent and effective therapeutic strategies for the relapsed myeloma setting, by documenting the latest clinical evidence from phase II and III clinical trials. Of note, new drugs, such as carfilzomib, ixazomib, pomalidomide, daratumumab and elotuzumab, alone or in combinations in doublet or triplet regimens, have greatly increased the treatment armamentarium against myeloma. Expert Commentary: Impressive results have been obtained with new drugs in relapsed patients. Besides number of prior therapies and previous response, other factors play a crucial role in the selection of therapy. Re-challenge with previous drugs can be adopted if previous responses lasted at least 6 months and therapy had induced low toxicity. Patients' risk status can further help to appropriately select therapy at relapse, and clinical trials will allow physicians to use newer targeted therapies and immune-therapies, thus delaying palliative approaches to later relapse stages.
- Hypothyroidism after Radiation Therapy for Childhood Cancer: A Report from the Childhood Cancer Survivor Study. [Journal Article]
- RRRadiat Res 2018 May 15
- While thyroid cancer risks from exposure to ionizing radiation early in life are well characterized quantitatively, the association of radiation with nonmalignant, functional thyroid disorders has be...
While thyroid cancer risks from exposure to ionizing radiation early in life are well characterized quantitatively, the association of radiation with nonmalignant, functional thyroid disorders has been less studied. Here, we report on a risk analysis study of hypothyroidism with radiation dose to the thyroid gland and the hypothalamic-pituitary axis among survivors of childhood cancer. Utilizing data from the Childhood Cancer Survivor Study, a cohort of 14,364 five-year survivors of childhood cancer diagnosed at 26 hospitals in the U.S. and Canada between 1970 and 1986 and followed through 2009, the occurrence of hypothyroidism was ascertained among 12,015 survivors through serial questionnaires. Radiation doses to the thyroid gland and pituitary gland were estimated from radiotherapy records. Binary outcome regression was used to estimate prevalence odds ratios for hypothyroidism at five years from diagnosis of childhood cancer and Poisson regression to model incidence rate ratios (RR) after the first five years. A total of 1,193 cases of hypothyroidism were observed, 777 (65%) of which occurred five or more years after cancer diagnosis. The cumulative proportion affected with hypothyroidism (prevalence at five years after cancer diagnosis plus incidence through 30 years after cancer diagnosis) was highest among five-year survivors of Hodgkin lymphoma (32.3%; 95% CI: 29.5-34.9) and cancers of the central nervous system (17.7%; 95% CI: 15.2-20.4). The incidence rate was significantly associated with radiation dose to the thyroid and pituitary. The joint association of hypothyroidism with thyroid and pituitary dose was sub-additive for pituitary doses greater than 16 Gy. In particular, a very strong thyroid radiation dose dependence at low-to-moderate pituitary/hypothalamic doses was diminished at high pituitary doses. Radiation-related risks were higher in males than females and inversely associated with age at exposure and time since exposure but remained elevated more than 25 years after exposure. Our findings indicated that hypothyroidism was significantly associated with treatment with bleomycin (RR = 3.4; 95% CI: 1.6-7.3) and the alkylating agents cyclohexyl-chloroethyl-nitrosourea (CCNU) (RR = 3.0; 95% CI: 1.5-5.3) and cyclophosphamide (RR = 1.3; 95% CI: 1.0-1.8), with a significant dose response for CCNU ( P < 0.01). The risk of hypothyroidism among childhood cancer survivors treated with radiation depends both on direct, dose-dependent radiation-induced damage to the thyroid gland and on dose-dependent indirect effects secondary to irradiation of the hypothalamic-pituitary axis. The dose-response relationship for each site depends on dose to the other. Radiation-related risk persists for more than 25 years after treatment. Treatment with certain chemotherapy agents may increase the risk of hypothyroidism.
- Emerging Cellular Therapies for Glioblastoma Multiforme. [Review]
- CCureus 2018 Mar 11; 10(3):e2305
- Glioblastoma multiforme (GBM) is the most common type of malignant primary brain cancer in adults. It is composed of highly malignant cells that display metastatic and angiogenic characteristics, mak...
Glioblastoma multiforme (GBM) is the most common type of malignant primary brain cancer in adults. It is composed of highly malignant cells that display metastatic and angiogenic characteristics, making it resistant to current first-line chemotherapy with temozolomide, an alkylating agent. Despite many years of research, GBM remains poorly responsive to multiple available therapies, giving GBM patients, who receive the conventional combination of chemoradiotherapies and surgical resection, a dismal prognosis. There is growing evidence that the conventional systemic chemotherapeutic agents for GBM are ineffective in improving the disease progression. We aim to explore the emerging cellular therapies which may play a significant role in treating GBM.
- Inhibition of the PI3K but not the MEK/ERK pathway sensitizes human glioma cells to alkylating drugs. [Journal Article]
- CCCancer Cell Int 2018; 18:69
- CONCLUSIONS: Temozolomide treatment naive and TMZ resistant GBM biopsies show a distinct activation pattern of the MEK/ERK and PI3K signaling cascades indicating a role of these pathways in resistance development. Both pathways are also activated in GBM cell lines, however, only the PI3K pathway seems to play a crucial role in resistance to alkylating agents and might serve as drug target for chemosensitization.
- New antineoplastic agent based on a dibenzoylmethane derivative: Cytotoxic effect and direct interaction with DNA. [Journal Article]
- BCBiophys Chem 2018 May 03; 239:1-6
- Melanoma accounts for only 4% of all skin cancers but is among the most lethal cutaneous neoplasms. Dacarbazine is the drug of choice for the treatment of melanoma in Brazil through the public health...
Melanoma accounts for only 4% of all skin cancers but is among the most lethal cutaneous neoplasms. Dacarbazine is the drug of choice for the treatment of melanoma in Brazil through the public health system mainly because of its low cost. However, it is an alkylating agent of low specificity and elicits a therapeutic response in only 20% of cases. Other drugs available for the treatment of melanoma are expensive, and tumor cells commonly develop resistance to these drugs. The fight against melanoma demands novel, more specific drugs that are effective in killing drug-resistant tumor cells. Dibenzoylmethane (1,3-diphenylpropane-1,3-dione) derivatives are promising antitumor agents. In this study, we investigated the cytotoxic effect of 1,3-diphenyl-2-benzyl-1,3-propanedione (DPBP) on B16F10 melanoma cells as well as its direct interaction with the DNA molecule using optical tweezers. DPBP showed promising results against tumor cells and had a selectivity index of 41.94. Also, we demonstrated the ability of DPBP to interact directly with the DNA molecule. The fact that DPBP can interact with DNA in vitro allows us to hypothesize that such an interaction may also occur in vivo and, therefore, that DPBP may be an alternative to treat patients with drug-resistant melanomas. These findings can guide the development of new and more effective drugs.
- Survival and Prognostic Factors in Mixed Cryoglobulinemia: Data from 246 Cases. [Journal Article]
- DDiseases 2018 May 03; 6(2)
- CONCLUSIONS: From our data, antiviral therapy is the first-line therapy in HCV-related MC, whereas steroids, alkylating agents and Rituximab should be considered as a second-line therapy. Given the heterogeneity of the disease, the role of these different therapeutic strategies should be checked in randomized controlled trials.
- Impact of ovarian transposition before pelvic irradiation on ovarian function among long-term survivors of childhood Hodgkin lymphoma: A report from the St. Jude Lifetime Cohort Study. [Journal Article]
- PBPediatr Blood Cancer 2018 May 11; :e27232
- CONCLUSIONS: OT did not appear to modify risk of POI in this historic cohort of long-term survivors of HL treated with gonadotoxic therapy. Modern fertility preservation modalities, such as mature oocyte cryopreservation, should be offered to at-risk patients whenever feasible.
- Delayed Complications and Long-term Management of Sulfur Mustard Poisoning: Recent Advances by Iranian Researchers (Part I of II). [Review]
- IJIran J Med Sci 2018; 43(2):103-124
- Chemical warfare agents are the most brutal weapons among the weapons of mass destruction. Sulfur mustard (SM) is a potent toxic alkylating agent known as "the King of the Battle Gases". SM has been ...
Chemical warfare agents are the most brutal weapons among the weapons of mass destruction. Sulfur mustard (SM) is a potent toxic alkylating agent known as "the King of the Battle Gases". SM has been the most widely used chemical weapon during the wars. It was widely used in World War I. Thereafter, it was extensively employed by the Iraqi troops against the Iranian military personnel and even civilians in the border cities of Iran and Iraq in the period between 1983 and 1988. Long-term incapacitating properties, significant environmental persistence, lack of an effective antidote, and relative ease of manufacturing have kept SM a potential agent for both terrorist and military uses. Even 3 decades after SM exposure, numerous delayed complications among Iranian victims are still being reported by researchers. The most common delayed complications have been observed in the respiratory tracts of chemically injured Iranian war veterans. Also, skin lesions and eye disorders have been observed in most Iranian SM-exposed war veterans in the delayed phase of SM intoxication. Thus, extensive research has been conducted on Iranian war veterans during the past decades. Nevertheless, major gaps still continue to exist in the SM literature. Part I of this paper will discuss the delayed complications and manifestations of exposure to SM among Iranian victims of the Iran-Iraq conflict. Part II, which will appear in the next issue of Iran J Med Sci, will discuss the long-term management and therapy of SM-exposed patients.
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- Anterior mediastinal Hodgkin lymphoma presenting as an extremely hypervascular tumor on computed tomography: A case report. [Case Reports]
- MMedicine (Baltimore) 2018; 97(19):e0607
- CONCLUSIONS: This presentation of HL as an extremely hypervascular anterior mediastinal mass on CT imaging has not been previously reported in the literature. This case suggests that HL should be included in the differential diagnosis of a hypervascular anterior mediastinal mass, especially if the patient is a young adult.