In one study, 34 Turner syndrome girls without overt evidence of these tumors were found at preventative surgery to have a gonadoblastoma (7 cases), dysgerminoma (1 case), or non-specific in situ gonadal neoplasm (1 case). Turner syndrome girls with this sSMC otherwise have typical features of the Turner syndrome except for a minority who also have hirsutism and/or clitoral enlargement. Surgical removal of the gonads has been recommended to remove the threat of developing these sSMC-associated neoplasms. Tuner syndrome individuals with an sSMC that lacks the SRY gene are not at an increased risk of developing these cancers. Sensory
Hearing loss is common in Turner syndrome. Though at birth hearing is generally normal, chronic middle ear problems are frequent throughout childhood, which can cause permanent conductive hearing loss. In adulthood, sensorineural hearing loss occurs more often than in 46,XX women and at younger ages; though differing thresholds of hearing loss make it difficult to compare between studies, younger adult women with Turner syndrome are routinely found to have disproportionate rates of hearing issues, with sometimes up to half of women in their 20s and 30s having poor hearing. This hearing loss is progressive; at the age of 40, women with Turner syndrome have equivalent hearing loss to 46,XX women aged 60, on average. Cohort studies imply hearing loss may be more common in women who also have metabolic syndrome. The high prevalence of sensorineural hearing loss in Turner syndrome appears to be related to SHOX deficiency.Ocular and visual disorders are also increased in prevalence in Turner syndrome.
Lurbinectedin, sold under the brand name Zepzelca, is a medication used for the treatment of small cell lung cancer.The most common side effects include leukopenia, lymphopenia, fatigue, anemia, neutropenia, increased creatinine, increased alanine aminotransferase, increased glucose, thrombocytopenia, nausea, decreased appetite, musculoskeletal pain, decreased albumin, constipation, dyspnea, decreased sodium, increased aspartate aminotransferase, vomiting, cough, decreased magnesium and diarrhea.Lurbinectedin is a synthetic tetrahydropyrrolo [4,3,2-de]quinolin-8(1H)-one alkaloid analogue with potential antineoplastic activity. Lurbinectedin covalently binds to residues lying in the minor groove of DNA, which may result in delayed progression through S phase, cell cycle arrest in the G2/M phase and cell death.Lurbinectedin was approved for medical use in the United States in June 2020. Medical uses
Lurbinectedin is indicated for the treatment of adults with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Structure
Lurbinectedin is structurally similar to trabectedin, although the tetrahydroisoquinoline present in trabectedin is replaced with a tetrahydro β-carboline which enables lurbinectedin to exhibit increased antitumor activity compared with trabectedin. Synthesis
Synthesis of lurbinectedin starts from small, common starting materials that require twenty-six individual steps to produce the drug with overall yield of 1.6%. Mechanism of action
According to PharmaMar, lurbinectedin inhibits the active transcription of the encoding genes. This has two consequences. It promotes tumor cell death and normalizes the tumor microenvironment. Active transcription is the process by which there are specific signal where information contained in the DNA sequence is transferred to an RNA molecule. This activity depends on the activity of an enzyme called RNA polymerase II.