Homeobox (HOX) genes are evolutionarily conserved genes encoding transcription factors that regulate mammalian embryonic growth and development of the urogenital tract. In both humans and mice, HOXA11 persists in the adult reproductive tract and is thought to play an important role in maintaining tissue developmental plasticity by regulating the expression of genes involved in extracellular matrix metabolism in the reproductive organs. Previously, we have shown that HOXA11 is necessary for development of the uterosacral ligaments in mice and is deficient in women with pelvic organ prolapse. Therefore, we hypothesized that Hoxa11 regulates the synthesis and/or metabolism of collagens in the uterosacral ligaments and uterus, and tested this by establishing an in utero and peritoneal Hoxa11 gene knockdown system in C57/BL6 mice using vectors bearing Hoxa11 short hairpin RNA. Specific knockdown of Hoxa11 transcripts and protein levels were confirmed versus control vectors. Protein and mRNA expression of collagen types I and III exhibited significant decreases following Hoxa11 knockdown according to Western blot analysis and real-time PCR. Tissue inhibitor of matrix metalloproteinase 1 (MMP1) expression also exhibited a significant decrease. Gelatinase zymography confirmed increases in pro-MMP2 and MMP9, as well as activated MMP2, following Hoxa11 knockdown. These results reveal that Hoxa11 knockdown in the uterosacral ligaments and uterus increases extracellular matrix degradation. More importantly, it suggests a mechanism in the weakening of the pelvic floor support in women, because decreased HOXA11 gene expression has been reported to be associated with decreased collagen and increased MMP2 expression in the uterosacral ligaments of women with pelvic organ prolapse.
Adenosquamous carcinoma is an extremely rare and lethal subtype of prostate cancer affecting an estimated 0.03 per million men annually. It has been associated with prior hormone therapy for prostate adenocarcinoma. We present a case of de novo adenosquamous carcinoma of the prostate treated with a multimodal approach including surgery, androgen-deprivation therapy, chemotherapy, and radiation.
Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. Although laparoscopy has been widely adopted for management of benign adrenal tumors, minimally invasive surgery for ACC remains controversial. Retrospective analyses, frequently with fewer than one hundred participants, comprise the majority of the literature. High-quality data regarding the optimal surgical approach for ACC are lacking due to the rarity of the disease and the fact that determination of tumor type (e.g., adenoma or carcinoma) is determined after adrenalectomy, since adrenal tumors are generally not biopsied. While the benefits of minimally invasive surgery including lower intra-operative blood loss and decreased hospital length-of-stay have been consistently demonstrated, clinical equipoise for long-term survival and recurrence outcomes between open and minimally invasive adrenalectomy (MIA) remains. This review examines retrospective studies that directly compare patients with ACC who underwent either open or laparoscopic adrenalectomy, and considers these findings in the context of current guideline recommendations for surgical management of ACC.
A 52-year-old gentleman presented with recurrent hematospermia. Further history revealed recent onset of constipation and difficulty voiding. Rectal examination revealed a firm, polypoid mass and colonoscopy showed suspicious, ulcerated lesions of the rectal mucosa with narrowing of the rectal vault. Pathology demonstrated transitional cell carcinoma of the rectum. While transitional cell carcinoma is a common genitourinary cancer, its presence in the anus and rectum is exceedingly rare. Furthermore, hematospermia is generally not associated with malignancy. This case is a remarkable example of two pathologic processes presenting in rare form and underscores the value of a thorough investigation of hematospermia when associated with other clinical symptoms.
Unknown to many, the prototype of such museum was hidden in the house of unlike scientist in the Dutch city of Delft.METHODS: Review of historical papers and Transactions of the Royal Society of London RESULTS: In 1673, lens crafter and amateur microscopist Anthony Van Leeuwenhoek suddenly became a widely known scientist, whose observations were published in the Philosophical Transactions of the Royal Society of London. This elite group of "virtuous and learned men" promoted empirical experimentation and offered its membership to accomplished scientists and educated men. Leeuwenhoek did not fit these requirements. He often has been dismissed as a dilettante, his work denigrated and disputed as superficial and chaotic .But his revolutionary discoveries and quality of microscopic observation were unparalleled.Leeuwenhoek had profound impact on future medicine not only by his famous letters to Royal Society, but direct promotion of new science. Secretive about his work, Leeuwenhoek made huge number of microscopes for a simple reason. In his house, Leeuwenhoek created unique collection of selected microscopic specimens, each fixed to its own microscope and ready for presentation.Leeuwenhoek hidden museum was open to educated visitors . He surprised them with hundreds of unreal objects from the brave new microscopic world. The collection was seen by people who later played an important role in the progress of medicine: six European kings, Russian Czar Peter the Great (the only one who got 2 microscopes as a present), celebrated physicians, scientists and philosophers: Ruysch,
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