Unexpected dearomatization of -protected 5-aminopyrazoles at ambient temperature: a simple route to highly functionalized pyrazolines.

We present a new strategy for the dearomatized hydroxylation of 5-aminopyrazoles using a hypervalent iodine reagent at room temperature. This method produces a series of 4-hydroxy-5-iminopyrazolines with good to excellent yields within 2 hours. Additionally, we demonstrate a domino reaction for the synthesis of 4-hydroxy-pyrazolones.

Exogenous APN protects normal tissues from radiation-induced oxidative damage and fibrosis in mice and prostate cancer patients with higher levels of APN have less radiation-induced toxicities.

Radiation causes damage to normal tissues that leads to increased oxidative stress, inflammation, and fibrosis, highlighting the need for the selective radioprotection of healthy tissues without hindering radiotherapy effectiveness in cancer. This study shows that adiponectin, an adipokine secreted by adipocytes, protects normal tissues from radiation damage invitro and invivo. Specifically, adiponectin (APN) reduces chronic oxidative stress and fibrosis in irradiated mice.

Efficacy of Voice Therapy in Rehabilitation of Muscle Tension Dysphonia in Patients of Nonlaryngeal Head and Neck Cancer: A Sequelae of Chemoradiotherapy.

The association of voice disorders in laryngeal cancers has been studied extensively; however Dysphonia associated with chemo-radiation in non laryngeal Head and Neck cancer (HNC) is a new area of practice in voice clinics. This study thus aimed to evaluate the efficacy of voice rehabilitation among non-laryngeal HNC survivors who were treated with curative RadioTherapy (RT)/Chemoradiotherapy (CRT) in adjunct with or without surgery. This tertiary institutional assessor blinded quasi experimental study after inclusion and exclusion criteria consisted of a study cohort of 128 patients who within 1-3 months of completion of treatment for HNC reported to the laryngology clinic for voice complaints and throat discomfort.

Muscle Tension Dysphonia: A Sequeale of Chemoradiotherapy in Patients of Head and Neck Cancer.

It's very important to demarcate that voice is the production of sound by the larynx while speech is articulation of the produced sound by tongue movements, soft palate and the lips. Mucositis, dysphagia, change in speech and voice are the common sequelae of Radiotherapy (RT) alone or in combination with chemotherapy (CRT) which is commonly used in the treatment of head and neck cancer (HNC). The aim of this study was to investigate the patient-reported voice impairment among non laryngeal head and neck cancer survivors who were treated with curative RT/CRT with or without surgery.

Expression of Cyclin-D1 and p53 as Prognostic Markers in Treatment of Oral Squamous Cell Carcinoma.

Cyclin D1 and p53 play an important role in tumorigenesis of human cancers. The present study aims to evaluate cyclin D1 and p53 expression in resectable OSCC, and to determine their prognostic significance at the end of 5 year follow-up: A total of 100 patients aged 31-74 years, stage 3/4 were recruited. Cyclin D1 and p53 expression in the tumour tissue was estimated by IHC and was statistically correlated with demographic and clinicopathological data and prognosis was evaluated at the end of 5 year outcome.

Evaluation of Tongue Functions After Free Flap Reconstruction.

Squamous cell carcinoma of the tongue is the most common malignancy of the oral cavity, the lateral border being the commonest site. The treatment strategies mandate surgery followed by appropriate reconstruction as the first line of management. There are many suitable methods of reconstruction of tongue defects after surgery, but the principle of an ideal reconstruction method should provide not only satisfactory structural cosmesis, but also good restoration of function.

NRF2: A crucial regulator for mitochondrial metabolic shift and prostate cancer progression.

Metabolic alterations are a common survival mechanism for prostate cancer progression and therapy resistance. Oxidative stress in the cellular and tumor microenvironment dictates metabolic switching in the cancer cells to adopt, prosper and escape therapeutic stress. Therefore, regulation of oxidative stress in tumor cells and in the tumor-microenvironment may enhance the action of conventional anticancer therapies.

Prostate cancer addiction to oxidative stress defines sensitivity to anti-tumor neutrophils.

Bone metastatic prostate cancer (BM-PCa) remains one of the most difficult cancers to treat due to the complex interactions of cancer and stromal cells. We previously showed that bone marrow neutrophils elicit an anti-tumor immune response against BM-PCa. Further, we demonstrated that BM-PCa induces neutrophil oxidative burst, which has previously been identified to promote primary tumor growth of other cancers, and a goal of this study was to define the importance of neutrophil oxidative burst in BM-PCa.

MnTE-2-PyP protects fibroblast mitochondria from hyperglycemia and radiation exposure.

Radiation is a common anticancer therapy for prostate cancer, which transforms tumor-associated normal fibroblasts to myofibroblasts, resulting in fibrosis. Oxidative stress caused by radiation-mediated mitochondrial damage is one of the major contributors to fibrosis. As diabetics are oxidatively stressed, radiation-mediated reactive oxygen species cause severe treatment failure, treatment-related side effects, and significantly reduced survival for diabetic prostate cancer patients as compared to non-diabetic prostate cancer patients.

Copper-catalysed -arylation of 5-aminopyrazoles: a simple route to pyrazolo[3,4-]indoles.

A copper-catalysed intramolecular N-arylation of 5-aminopyrazoles is demonstrated for the first time. Highly substituted pyrazolo[3,4-b]indoles are synthesized. In particular, the indole core is decorated with halogens and alkyl and methoxy groups.

MnTE-2-PyP Suppresses Prostate Cancer Cell Growth via HO Production.

Prostate cancer patients are often treated with radiotherapy. MnTE-2-PyP, a superoxide dismutase (SOD) mimic, is a known radioprotector of normal tissues. Our recent work demonstrated that MnTE-2-PyP also inhibits prostate cancer progression with radiotherapy; however, the mechanisms remain unclear.

MnTE-2-PyP, a manganese porphyrin, reduces cytotoxicity caused by irradiation in a diabetic environment through the induction of endogenous antioxidant defenses.

Radiation is a common anticancer therapy for many cancer patients, including prostate cancer. Diabetic prostate cancer patients suffer from increased lymph node metastasis, tumor recurrence and decreased survival as compared to non-diabetic prostate cancer patients. These patients are also at increased risk for enhanced radiation-induced normal tissue damage such as proctitis.

Manganese porphyrin, MnTE-2-PyP, treatment protects the prostate from radiation-induced fibrosis (RIF) by activating the NRF2 signaling pathway and enhancing SOD2 and sirtuin activity.

Radiation therapy is a frequently used treatment for prostate cancer patients. Manganese (III) meso-tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP or T2E or BMX-010) and other similar manganese porphyrin compounds that scavenge superoxide molecules have been demonstrated to be effective radioprotectors and prevent the development of radiation-induced fibrosis (RIF). However, understanding the molecular pathway changes associated with these compounds remains limited for radioprotection.

A semiconducting supramolecular Co(ii)-metallohydrogel: an efficient catalyst for single-pot aryl-S bond formation at room temperature.

A novel mechanically stable supramolecular Co(ii)-metallohydrogel has been synthesized. Cobalt(ii) nitrate hexahydrate and monoethanolamine, as a low molecular weight organic gelator, are used to get the gel. The mechanical stability of the supramolecular hydrogel was analyzed.

Theoretical Study on the Mechanism of Rearrangement Reactions of Bicyclic Derivatives of Cyclopropane to Monocyclic Derivatives under the Catalysis of Pt-Salt.

In this paper, the mechanistic studies on the isomerization of hydroxyl and silyl derivatives of bicyclic cyclopropanes under the catalytic action of Zeise's salt have been reported. The catalytic activity of both the monomeric and the dimeric forms of Zeise's salt has been studied by applying the high-level quantum mechanical method. Results from this investigation reveal that the reaction goes favorably under the catalysis of the dimeric form of Zeise's salt.

p66Shc protein through a redox mechanism enhances the progression of prostate cancer cells towards castration-resistance.

Prostate cancer (PCa) remains the second leading cause of cancer-related deaths in U.S. men due to the development of the castration-resistant (CR) PCa phenotype.

Au-Catalyzed Hexannulation and Pt-Catalyzed Pentannulation of Propargylic Ester Bearing a 2-Alkynyl-phenyl Substituent: A Comparative DFT Study.

The mechanistic pathways of metal-catalyzed pentannulation and hexannulation of aromatic enediyne were studied quantum mechanically with Pt and Au salts. In agreement with the experimental facts, our result shows that the pentannulation favors over the hexannulation under Pt-catalyzed conditions and the reverse possibility favors when the Pt salt is replaced with an Au one. The Pt-catalyzed reaction involves a long-range acyl migration that follows the cyclization step.

The Addition of Manganese Porphyrins during Radiation Inhibits Prostate Cancer Growth and Simultaneously Protects Normal Prostate Tissue from Radiation Damage.

Radiation therapy is commonly used for prostate cancer treatment; however, normal tissues can be damaged from the reactive oxygen species (ROS) produced by radiation. In separate reports, we and others have shown that manganese porphyrins (MnPs), ROS scavengers, protect normal cells from radiation-induced damage but inhibit prostate cancer cell growth. However, there have been no studies demonstrating that MnPs protect normal tissues, while inhibiting tumor growth in the same model.

The SOD Mimic, MnTE-2-PyP, Protects from Chronic Fibrosis and Inflammation in Irradiated Normal Pelvic Tissues.

Pelvic radiation for cancer therapy can damage a variety of normal tissues. In this study, we demonstrate that radiation causes acute changes to pelvic fibroblasts such as the transformation to myofibroblasts and the induction of senescence, which persist months after radiation. The addition of the manganese porphyrin, MnTE-2-PyP, resulted in protection of these acute changes in fibroblasts and this protection persisted months following radiation exposure.

MnTE-2-PyP Treatment, or NOX4 Inhibition, Protects against Radiation-Induced Damage in Mouse Primary Prostate Fibroblasts by Inhibiting the TGF-Beta 1 Signaling Pathway.

Prostate cancer patients who undergo radiotherapy frequently suffer from side effects caused by radiation-induced damage to normal tissues adjacent to the tumor. Exposure of these normal cells during radiation treatment can result in tissue fibrosis and cellular senescence, which ultimately leads to postirradiation-related chronic complications including urinary urgency and frequency, erectile dysfunction, urethral stricture and incontinence. Radiation-induced reactive oxygen species (ROS) have been reported as the most potent causative factor for radiation damage to normal tissue.

MnTE-2-PyP modulates thiol oxidation in a hydrogen peroxide-mediated manner in a human prostate cancer cell.

To improve the treatment of advanced prostate cancer, the development of effective and innovative antitumor agents is needed. Our previous work demonstrated that the ROS (reactive oxygen species) scavenger, MnTE-2-PyP, inhibited human prostate cancer growth and also inhibited prostate cancer migration and invasion. We showed that MnTE-2-PyP treatment altered the affinity of the histone acetyltransferase enzyme, p300, to bind to DNA.

Lactate induced HIF-1α-PRMT1 cross talk affects MHC I expression in monocytes.

Tumor infiltrating monocytes play a crucial role in tumor immune surveillance. As lactate is an important component of the tumor milieu, we investigated its role in the transcriptional regulation of MHC I which is crucial for mounting effective immune responses against tumors. Lactate elevated MHC class I expression in monocytes.

MnTnBuOE-2-PyP protects normal colorectal fibroblasts from radiation damage and simultaneously enhances radio/chemotherapeutic killing of colorectal cancer cells.

Manganese porphyrins have been shown to be potent radioprotectors in a variety of cancer models. However, the mechanism as to how these porphyrins protect normal tissues from radiation damage still remains largely unknown. In the current study, we determine the effects of the manganese porphyrin, MnTnBuOE-2-PyP, on primary colorectal fibroblasts exposed to irradiation.