ABSTRACT
Studies on the clinical profile of urothelial bladder cancer (UBC) have shown significant gender differences, namely, higher occurrence in males (male-to-female ratio of 3.5:1) and an advanced stage of disease at the time of diagnosis with rapid progression of the disease after initial diagnosis seen more commonly in females. The relationship between gender and UBC is complex and probably influenced by biological and epidemiological factors. Potential contributory factors such as sex steroid hormone pathway, gender difference in environmental carcinogen exposure, metabolic enzyme activity, and disparities in the intensity of diagnostic evaluation could probably explain the demographic trends in UBC. This comprehensive review of Medline publications during the period 2009-2019 attempts to identify the possible role of sex hormone receptors in gender variation and sexual dimorphism in the occurrence and progression of UBC. The clinical implications of identifying sex steroid receptors on factors such as disease prognostication and the therapeutic role of anti-androgens in the prevention and progression of UBC are critically reviewed. There is now significant evidence in literature to suggest the possible role of sex steroid hormone receptor-mediated signals in the genesis and progression of UBC. These receptors include androgen receptors, estrogen receptors, progesterone receptors, and various other orphan receptors. Excessive or reduced expression of these receptors, as well as alterations in their upstream or downstream pathways, correlate well with the clinical and therapeutic outcomes of UBC.
ABSTRACT
Use of exogenous estrogens in manipulating the androgenestrogen equilibrium was one of the earliest therapeutic strategies developed to treat prostate cancer which followed close on heels the discovery of hormone dependence of this tumor. Despite its well-documented benefit, estrogen therapy fell out of favor with the advent of other forms of androgen deprivation therapy (ADT) as the former registered a higher incidence of cardiovascular complications and poorer overall survival. Clearer understanding of the mechanism of action of estrogen coupled with the adoption of alternative routes of administration has triggered a renewed interest in estrogen therapy. Since then, many studies have not only proved the therapeutic benefit of estrogens but also explored the ways and means of minimizing the dreaded side effects deterring its use. Further, the fact that estrogen therapy offered a clear advantage of reduced cost of treatment over other treatments has led many countries to readopt it in the treatment of advanced prostatic cancer. We reviewed the published data on the use of estrogens in CRPC, which may affect its revival as an efficacious treatment option having minimal side effects, with modified dosage and route of administration. Estrogen therapy would be a less expensive option having equivalent or even better therapeutic effect than ADT in advanced carcinoma of prostate.
ABSTRACT
Massive bilateral renomegaly with maintained renal morphology in infants is a rare entity. We present the images of a A 9-month-old female child who presented with massive bilateral renomegaly with maintained renal morphology due to acute lymphoblastic leukemia.
ABSTRACT
In this paper, we report a theoretical investigation of the catalytic mechanism of peptide amidases that involve a Ser-(cis)Ser-Lys catalytic triad. Previous suggestions propose that these enzymes should follow a distinct catalytic mechanism from the one that is present in the classic Ser-His-Asp catalytic triad. The theoretical and computational results obtained in this work indicate the opposite idea, showing that both mechanisms are very similar and only few differences are observed between both reactions. The results reveal that the different alignment of the Ser-(cis)Ser-Lys catalytic triad in relation to the classical Ser-His-Asp triad may provide a better stabilisation of the reaction intermediates, and therefore make these enzymes catalytically more efficient. The catalytic mechanism has been determined at the M06-2X/6-311++G**//B3LYP/6-31G* level of theory and requires five sequential steps instead of the two that are generally proposed: (i) nucleophilic attack of serine on the carbonyl group of the substrate, forming the first tetrahedral intermediate, (ii) formation of an acyl-enzyme complex, (ii) release of an ammonia product, (iv) nucleophilic attack of a water molecule forming the second tetrahedral intermediate, and (iv) the release of the product of the reaction, the carboxylic acid. The computational results suggest that the rate-limiting step is the first one that requires an activation free energy of 15.93 kcal mol-1. This result agrees very well with the available experimental data that predict a reaction rate of 2200 s-1, which corresponds to a free energy barrier of 14 kcal mol-1.
Subject(s)
Amidohydrolases/chemistry , Amidohydrolases/metabolism , Models, Chemical , Peptides/chemistry , Catalysis , Water/chemistryABSTRACT
Ectopic scrotum is a rare congenital anomaly. Most common location is supra-inguinal. We present a case of left ectopic scrotum in a three year old boy with no associated congenital anomalies, who underwent successful scrotoplasty and orchiopexy.
ABSTRACT
Prostatic abscess rarely follows acute prostatitis and can sometimes lead to a fistula by breaking into the prostatic urethra, peri-rectal tissues, the perineum, or the rectum. We report a case of a prostatic abscess tracking into the bulbar urethra after a transurethral resection of the prostate. This created a fistula, mimicking a urethral duplication and leading to urinary incontinence.
ABSTRACT
Primary renal synovial sarcoma is a rare tumor having a specific chromosomal translocation t(X; 18) (p11.2; q11.2). The clinical features of this tumor and radiologic appearances are quite similar to those of renal cell carcinoma. Confirmatory diagnosis requires fluorescent in situ hybridization or reverse transcriptase polymerase chain reaction validation for differentiating the tumors from sarcomatoid renal cell carcinoma. We present a case of primary renal synovial sarcoma that was diagnosed in a middle-aged man.
ABSTRACT
Kidney volume is regarded as the most precise indicator of kidney size. However, volume assessment is not widely used clinically because its measurement is difficult due to the complex kidney shape. Apart from the conventional methods of measurement of renal dimensions from X-rays, ultrasound scan, computed tomography scan and magnetic resonance imaging have evolved as the three best modalities for this purpose currently. Assessment of kidney size should also be made individually since many factors like body mass index, height, gender, age, position of kidneys, sex, stenoses and number of renal arteries influence the measurements. In this paper, we have critically analysed the advantages and disadvantages of the various methods of renal morphometry, by reviewing the literature spanning over the period of 1976 - 2009.
ABSTRACT
The goal of primary chemoprevention is to decrease the incidence of a given cancer, simultaneously reducing treatment-related adverse events, cost of treatment of the disease and mortality. Prostate cancer is an attractive and appropriate target for primary prevention because of its high incidence and prevalence, increased disease-related mortality, long latency and molecular pathogenesis and epidemiological data indicating that modifiable environmental factors may decrease risk. Various agents have been suggested to prevent prostate cancer and many clinical trials are currently on. Ultimately the adoption of a preventive strategy hinges on its potential benefits weighed against the potential risks of the specific agents used. This article is aimed to examine the experimental and epidemiological data spanning a period of 1998 to 2007, demonstrating the chemopreventive activity, safety and toxicity of various nutritional elements and other agents that can help prevent prostate cancer and/or slow disease progression.
