Omics sciences and precision medicine in breast and ovarian cancer.

Background: Human breast carcinoma is a complex disease, affecting 1 in 8 women worldwide. The seriousness of the disease increases when the definite cause of the disease remains obscure, thus making prognosis challenging. Researchers are emphasizing on adapting more advanced and targeted therapeutic approaches to address the multifaceted impacts of the disease. Hence, modern multi-omics systems have gained popularity among clinicians, as they offer insights into the genomic, pharmacogenomic, metabolomic, and microbiomic factors, thus allowing researchers to develop targeted and personalized approaches for breast cancer prevention and early detection, and eventually improving patient outcomes. Aim: The primary focus of this study is to elucidate, through the integration of multi-omics research findings, the inherent molecular origins of diverse subtypes of breast cancer and to evaluate the effectiveness of these findings in reducing breast cancer-related mortalities. Methods: Thorough investigation was conducted by reviewing reputable and authoritative medical journals, e-books, and online databases dedicated to cancer research. The Mendelian inheritance in man database (OMIM) was used to scrutinize specific genes and their respective loci associated with the development of different types of breast cancer. Results: Our present research revealed the holistic picture of sundry molecular, genomic, pharmacogenomic, metabolomic, and microbiomic features of breast cancer. Such findings, like genetic alterations in highly penetrant genes, plus metabolomic and microbiomic signatures of breast cancer, unveil valuable insights and show great potential for multi-omics research in breast oncology. Conclusion: Further research in omics sciences pertaining to breast cancer are at the forefront of shaping precise treatment and bolstering patient survival.

On the dynamics of water molecules at the protein solute interfaces.

Proteins, with the large variety of chemical groups they present at their molecular surface, are a class of molecules which can be very informative on most of the possible solute-solvent interactions. Hen egg white lysozyme has been used as a probe to investigate the complex solvent dynamics occurring at the protein surface, by analysing the results obtained from Nuclear Magnetic Resonance, X-ray diffractometry and Molecular Dynamics simulations. A consistent overall picture for the dynamics of water molecules close to the protein is obtained, suggesting that a rapid exchange occurs, in a picosecond timescale, among all the possible hydration surface sites both in solution and the solid state, excluding the possibility that solvent molecules can form liquid-crystal-like supramolecular adducts, which have been proposed as a molecular basis of 'memory of water'.

Should patients with combined colonic inertia and nonrelaxing pelvic floor undergo subtotal colectomy?

PURPOSE: Treatment of severe constipation caused by combined colonic inertia and nonrelaxing pelvic floor is controversial. This study is designed to evaluate the outcome of preoperative biofeedback and subtotal colectomy for patients with combined colonic inertia and nonrelaxing pelvic floor. METHODS: One hundred six patients who underwent subtotal colectomy for intractable constipation from 1982 through 1995 answered a detailed questionnaire regarding postoperative bowel function, symptoms of abdominal pain and bloating, and degree of satisfaction after the operation. Sixteen of these patients had a combination of colonic inertia and nonrelaxing pelvic floor diagnosed by transit marker study, electromyography, and defecography. These patients completed preoperative biofeedback training. RESULTS: Electromyographic relaxation of pelvic floor musculature was demonstrated after the biofeedback treatment in all patients, but symptoms of difficult evacuation persisted. Postoperatively, seven patients (43 percent) had complete resolution of symptoms of constipation or difficult evacuation. Six patients still complained of incomplete evacuation that was severe in two and unresponsive to postoperative biofeedback. Three patients (18 percent) complained of diarrhea (>5 bowel movements per day) and incontinence of liquid stools (at least one episode a week). Nine patients (56 percent) were satisfied despite persistent symptoms. CONCLUSIONS: Subtotal colectomy can improve some symptoms in patients with slow transit constipation and nonrelaxing pelvic floor. However, incomplete evacuation persists in a significant number of patients and almost one-half of patients are dissatisfied with their surgery.

Italian style brewed coffee: effect on serum cholesterol in young men.

BACKGROUND: Increases in blood lipids have been observed in humans when coffee is brewed by the boiling method. The purpose of this study was to evaluate if giving up Italian coffee might reduce blood cholesterol levels. METHODS: Eighty-four normolipidaemic young adult males, after a 3-week baseline (BL), were randomly assigned to three different regimens of coffee consumption: espresso (E), mocha (M), and no coffee, but tea (T). The average coffee consumption during intervention (I) was 3.1 +/- 1.2 and 2.8 +/- 1.1 cups per day for espresso and mocha group respectively (espresso: 25-35 ml/cup; mocha: 40-50 ml/cup). Total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides were measured eight times during the study. Dietary pattern, alcohol consumption, smoking habits, drug use, and anthropometric data were also recorded. RESULTS: The changes observed in serum cholesterol concentration between baseline and intervention were not statistically different in all groups. The changes were 0.0 mmol/l (T), +0.01 mmol/l (E) and +0.05 mmol/l (M) for total serum cholesterol; 0 mmol/l (T), -0.02 mmol/l (E) and -0. 03 mmol/l (M) for HDL-C; -0.13 mmol/l (T), +0.02 mmol/l (E) and -0. 05 mmol/l (M) for LDL-C. Serum triglycerides showed a significant increase during intervention (P < 0.01 by ANOVA) in all groups with a change of 0.18 mmol/l, 0.18 mmol/l and 0.22 mmol/l, for tea, espresso and mocha group respectively. CONCLUSIONS: The results indicate that coffee brewed in the Italian way does not alter blood levels of total cholesterol, HDL-cholesterol and LDL-cholesterol, since no significant differences were observed in these blood parameters after a 6-week break from coffee consumption.

Preoperative adjuvant radiation with chemotherapy for rectal cancer: its impact on stage of disease and the role of endorectal ultrasound.

BACKGROUND: Preoperative adjuvant radiation combined with chemotherapy is a recent development in the management of patients with rectal cancer invading perirectal tissue and regional lymph nodes. This study was performed to assess the impact of preoperative adjuvant therapy in patients judged by endorectal ultrasound to have extramural invasion of rectal cancer and/or regional lymph node involvement on tumor regression in bowel wall and lymph nodes. The predictive value of ultrasound in staging wall penetration and lymph node involvement after preoperative adjuvant therapy was also assessed. METHODS: Patients (n = 43) were selected by ultrasound to have preoperative irradiation (4,500-5,040 cGy over 5-6 weeks). In 30 patients this was combined with 5-fluorouracil, 370 mg/m(2), for 5 days in the first and last weeks of irradiation. Pretreatment ultrasound was compared with pathologic findings in the resected specimen in all patients. Twenty-one were assessed by ultrasound after adjuvant therapy and findings compared with histology. RESULTS: Downstaging was seen in 23 (53%) patients with wall invasion and in 23 (72%) of 32 patients with lymph node involvement. Overall, downstaging was achieved in 30 (70%). Positive predictive values of ultrasound after irradiation were 72% and 56% for wall penetration and lymph node status, respectively. Negative predictive values of ultrasound after irradiation were 100% and 82%, respectively. CONCLUSION: In the majority of patients with rectal cancer invading perirectal tissues or lymph nodes, lesions may be downstaged by preoperative adjuvant therapy. Endorectal ultrasound after adjuvant therapy for rectal cancer is of a lesser predictive value chiefly because of overstaging.

Antinociceptive activity of salmon calcitonin: electrophysiological correlates in a rat chronic pain model.

Experimental and clinical evidence testifies to an antinociceptive action of salmon calcitonin (sCT), administered in different ways, on the central nervous system. These studies were performed almost exclusively in acute pain models. The purpose of the present study was to investigate the effects of sCT, injected directly into the lateral cerebral ventriculi, on the firing of single nociceptive thalamic neurons, detected by electrophysiological techniques in an experimental model of prolonged or chronic pain, such as rats rendered arthritic by injection of Freund's adjuvant into the left hindfoot. The noxious test stimuli used were either extension or flexion of the ankle or mild lateral pressure on the heel. With increasing doses of sCT (5, 10, 20, 40 micrograms, 5 microliters/i.c.v.) it was possible to observe correspondingly increasing inhibitory and long-lasting effects on the evoked firing, with a significant dose-effect relationship. In agreement with electrophysiological findings, preliminary data, obtained with a patch clamp technique, on depression of calcium fluxes through neuronal membrane, induced by sCT, oriented the attention to a direct action of sCT on CNS.