Six-month depot formulation of leuprorelin acetate in the treatment of prostate cancer

Hormonal deprivation therapy is well established for the treatment of locally advanced and metastatic prostate cancer, as well as the adjuvant treatment of some patients with localized disease. Long-acting gonadotropin releasing hormone (GnRH) agonists have become a mainstay of androgen deprivation therapy, due to their efficacy, tolerability, and convenience of use. One-month, 3-month, and 4-month depot leuprorelin formulations are well established and widely used to this end. Recently, a 6-month depot leuprorelin has been approved for use in advanced and metastatic prostate cancer patients. With similar efficacy and side effect profiles to earlier formulations, 6-month depot leuprorelin is a convenient treatment option for these patients. This review will highlight the role of GnRH agonists in the treatment of prostate cancer with a focus on the clinical efficacy, pharmacology, and patient-focused outcomes of the newer 6-month 45 mg depot leuprorelin formulation in comparison to available shorter-acting products

DETERMINATION OF ELECTROMAGNETIC PARAMETERS OF A NEW METASURFACE COMPRISING OF SQUARE LOOP

In the present work, the reflection and transmission coefficients of new metasurface consisting of square loop structures have been analyzed to determine the electromagnetic parameters. In order to analyze the metasurface, a block of 3X3 cells has been placed centrally in a waveguide with a well defined boundary conditions and excitations which is a representative of infinite number of unit cells. The simulation results show that the effective permittivity and effective permeability of metasurface are negative imultaneously in the desired frequency range. The negative refractive index is confirmed by the overlapped region of negative effective permittivity and effective permeability

Clinical applications of custom-made vaginal cylinders constructed using three-dimensional printing technology.

PurposeThree-dimensional (3D) printing technology allows physicians to rapidly create customized devices for patients. We report our initial clinical experience using this technology to create custom applicators for vaginal brachytherapy.Material and methodsThree brachytherapy patients with unique clinical needs were identified as likely to benefit from a customized vaginal applicator. Patient 1 underwent intracavitary vaginal cuff brachytherapy after hysterectomy and chemotherapy for stage IA papillary serous endometrial cancer using a custom printed 2.75 cm diameter segmented vaginal cylinder with a central channel. Patient 2 underwent interstitial brachytherapy for a vaginal cuff recurrence of endometrial cancer after prior hysterectomy, whole pelvis radiotherapy, and brachytherapy boost. We printed a 2 cm diameter vaginal cylinder with one central and six peripheral catheter channels to fit a narrow vaginal canal. Patient 3 underwent interstitial brachytherapy boost for stage IIIA vulvar cancer with vaginal extension. For more secure applicator fit within a wide vaginal canal, we printed a 3.5 cm diameter solid cylinder with one central tandem channel and ten peripheral catheter channels. The applicators were printed in a biocompatible, sterilizable thermoplastic.ResultsPatient 1 received 31.5 Gy to the surface in three fractions over two weeks. Patient 2 received 36 Gy to the CTV in six fractions over two implants one week apart, with interstitial hyperthermia once per implant. Patient 3 received 18 Gy in three fractions over one implant after 45 Gy external beam radiotherapy. Brachytherapy was tolerated well with no grade 3 or higher toxicity and no local recurrences.ConclusionsWe established a workflow to rapidly manufacture and implement customized vaginal applicators that can be sterilized and are made of biocompatible material, resulting in high-quality brachytherapy for patients whose anatomy is not ideally suited for standard, commercially available applicators

Expeditious synthesis of isolated Steroids-Fluorine prodrugs, their single crystal X-ray crystallography, DFT studies and mathematical modeling

In the present research article, we have synthesized novel steroidal-fluorine prodrugs using cholesterol (1), stigmasterol (4) and hydrocortisone acetate (7) isolated from the flowers of Allamanda violacea. These isolated compounds were converted into their fluorinated prodrugs Cholest-5-en-3β-yl-2-fluoro-benzoate (2), Cholest-5-en-3β-yl-4-fluoro-benzoate (3), 24α-ethylcholest-5, 22E-dien-3β-yl-2-fluoro benzoate (5), 24α-ethylcholest-5, 22E-dien-3β-yl-4-fluoro benzoate (6), 11, 17-dihydroxy-21-(2-fluoro benzoyloxy)-pregn-4-en-3, 20-dione (8) and 11, 17-dihydroxy-21-(4-fluoro benzoyloxy)-pregn-4-en-3, 20-dione (9). We also synthesized fluorinated prodrugs 25R-spirost-5-en-3β-yl-2-fluoro-benzoate (11) and 25R-spirost-5-en-3β-yl-4-fluoro-benzoate (12) from diosgenin (10) a steroidal sapogenin. The structure and stereochemistry of 25R-spirost-5-en-3β-yl-4-fluoro-benzoate (12) was confirmed with help of single crystal X-ray crystallography. The characterization of compounds have been carried out with the help of 1H, 13C NMR, FT-IR spectroscopy and mass spectrometry. Density functional theory (DFT) with 6-31G (d, p) basis set and B3LYP functional has been used for the Quantum chemical calculations. Global reactivity descriptors have also been calculated to find the electrophilicity and nucleophilicity of a molecule. Dipole moment, polarizability and first static hyperpolarizability have been calculated to get NLO properties of synthesized prodrugs. Lastly a nonlinear mathematical model has been proposed and analyzed to study the effect of catalysts on these reactions. Local and global stability analysis of the mathematical model along with the persistence of the system was checked using theory of nonlinear ordinary differential equations

High resolution mapping of QTLs for fruit color and firmness in Amrapali/Sensation mango hybrids

IntroductionMango (Mangifera indica L.), acclaimed as the ‘king of fruits’ in the tropical world, has historical, religious, and economic values. It is grown commercially in more than 100 countries, and fresh mango world trade accounts for ~3,200 million US dollars for the year 2020. Mango is widely cultivated in sub-tropical and tropical regions of the world, with India, China, and Thailand being the top three producers. Mango fruit is adored for its taste, color, flavor, and aroma. Fruit color and firmness are important fruit quality traits for consumer acceptance, but their genetics is poorly understood.MethodsFor mapping of fruit color and firmness, mango varieties Amrapali and Sensation, having contrasting fruit quality traits, were crossed for the development of a mapping population. Ninety-two bi-parental progenies obtained from this cross were used for the construction of a high-density linkage map and identification of QTLs. Genotyping was carried out using an 80K SNP chip array.Results and discussionInitially, we constructed two high-density linkage maps based on the segregation of female and male parents. A female map with 3,213 SNPs and male map with 1,781 SNPs were distributed on 20 linkages groups covering map lengths of 2,844.39 and 2,684.22cM, respectively. Finally, the integrated map was constructed comprised of 4,361 SNP markers distributed on 20 linkage groups, which consisted of the chromosome haploid number in Mangifera indica (n =20). The integrated genetic map covered the entire genome of Mangifera indica cv. Dashehari, with a total genetic distance of 2,982.75 cM and an average distance between markers of 0.68 cM. The length of LGs varied from 85.78 to 218.28 cM, with a mean size of 149.14 cM. Phenotyping for fruit color and firmness traits was done for two consecutive seasons. We identified important consistent QTLs for 12 out of 20 traits, with integrated genetic linkages having significant LOD scores in at least one season. Important consistent QTLs for fruit peel color are located at Chr 3 and 18, and firmness on Chr 11 and 20. The QTLs mapped in this study would be useful in the marker-assisted breeding of mango for improved efficiency

Expeditious synthesis of isolated steroids-fluorine prodrugs, their single crystal X-ray crystallography, DFT studies and mathematical modeling

831-841In the present research article, we have synthesized novel steroidal-fluorine prodrugs using cholesterol (1), stigmasterol (4) and hydrocortisone acetate (7) isolated from the flowers of Allamanda violacea. These isolated compounds were converted into their fluorinated prodrugs Cholest-5-en-3β-yl-2-fluoro-benzoate (2), Cholest-5-en-3β-yl- 4-fluoro-benzoate (3), 24α-ethylcholest-5, 22E-dien-3β-yl-2-fluoro benzoate (5), 24α-ethylcholest-5, 22E-dien-3β-yl-4- fluoro benzoate (6), 11, 17-dihydroxy-21-(2-fluoro benzoyloxy)-pregn-4-en-3, 20-dione (8) and 11, 17-dihydroxy-21- (4-fluoro benzoyloxy)-pregn-4-en-3, 20-dione (9). We also synthesized fluorinated prodrugs 25R-spirost-5-en-3β-yl-2- fluoro-benzoate (11) and 25R-spirost-5-en-3β-yl-4-fluoro-benzoate (12) from diosgenin (10) a steroidal sapogenin. The structure and stereochemistry of 25R-spirost-5-en-3β-yl-4-fluoro-benzoate (12) was confirmed with help of single crystal X-ray crystallography. The characterizations of compounds have been carried out with the help of 1H, 13C NMR, FT-IR spectroscopy and mass spectrometry. Density functional theory (DFT) with 6-31G (d, p) basis set and B3LYP functional has been used for the quantum chemical calculations. Global reactivity descriptors have also been calculated to find the electrophilicity and nucleophilicity of a molecule. Dipole moment, polarizability and first static hyperpolarizability have been calculated to get NLO properties of synthesized prodrugs. Lastly a nonlinear mathematical model has been proposed and analyzed to study the effect of catalysts on these reactions. Local and global stability analysis of the mathematical model along with the persistence of the system is checked using theory of nonlinear ordinary differential equations

Clinical applications of custom-made vaginal cylinders constructed using three-dimensional printing technology

PURPOSE: Three-dimensional (3D) printing technology allows physicians to rapidly create customized devices for patients. We report our initial clinical experience using this technology to create custom applicators for vaginal brachytherapy. MATERIAL AND METHODS: Three brachytherapy patients with unique clinical needs were identified as likely to benefit from a customized vaginal applicator. Patient 1 underwent intracavitary vaginal cuff brachytherapy after hysterectomy and chemotherapy for stage IA papillary serous endometrial cancer using a custom printed 2.75 cm diameter segmented vaginal cylinder with a central channel. Patient 2 underwent interstitial brachytherapy for a vaginal cuff recurrence of endometrial cancer after prior hysterectomy, whole pelvis radiotherapy, and brachytherapy boost. We printed a 2 cm diameter vaginal cylinder with one central and six peripheral catheter channels to fit a narrow vaginal canal. Patient 3 underwent interstitial brachytherapy boost for stage IIIA vulvar cancer with vaginal extension. For more secure applicator fit within a wide vaginal canal, we printed a 3.5 cm diameter solid cylinder with one central tandem channel and ten peripheral catheter channels. The applicators were printed in a biocompatible, sterilizable thermoplastic. RESULTS: Patient 1 received 31.5 Gy to the surface in three fractions over two weeks. Patient 2 received 36 Gy to the CTV in six fractions over two implants one week apart, with interstitial hyperthermia once per implant. Patient 3 received 18 Gy in three fractions over one implant after 45 Gy external beam radiotherapy. Brachytherapy was tolerated well with no grade 3 or higher toxicity and no local recurrences. CONCLUSIONS: We established a workflow to rapidly manufacture and implement customized vaginal applicators that can be sterilized and are made of biocompatible material, resulting in high-quality brachytherapy for patients whose anatomy is not ideally suited for standard, commercially available applicators