Neoadjuvant Metformin Added to Systemic Therapy Decreases the Proliferative Capacity of Residual Breast Cancer.

The proliferative capacity of residual breast cancer (BC) disease indicates the existence of partial treatment resistance and higher probability of tumor recurrence. We explored the therapeutic potential of adding neoadjuvant metformin as an innovative strategy to decrease the proliferative potential of residual BC cells in patients failing to achieve pathological complete response (pCR) after pre-operative therapy. We performed a prospective analysis involving the intention-to-treat population of the (Metformin and Trastuzumab in Neoadjuvancy) METTEN study, a randomized multicenter phase II trial of women with primary, non-metastatic (human epidermal growth factor receptor 2) HER2-positive BC evaluating the efficacy, tolerability, and safety of oral metformin (850 mg twice-daily) for 24 weeks combined with anthracycline/taxane-based chemotherapy and trastuzumab (arm A) or equivalent regimen without metformin (arm B), before surgery.

Metformin induces a fasting- and antifolate-mimicking modification of systemic host metabolism in breast cancer patients.

Certain dietary interventions might improve the therapeutic index of cancer treatments. An alternative to the "drug plus diet" approach is the pharmacological reproduction of the metabolic traits of such diets. Here we explored the impact of adding metformin to an established therapeutic regimen on the systemic host metabolism of cancer patients.

The Allele of rs11212617 Associates With Higher Pathological Complete Remission Rate in Breast Cancer Patients Treated With Neoadjuvant Metformin.

The minor allele () of the single-nucleotide polymorphism (SNP) , located near the () gene, has been associated with an increased likelihood of treatment success with metformin in type 2 diabetes. We herein investigated whether the same SNP would predict clinical response to neoadjuvant metformin in women with early breast cancer (BC). DNA was collected from 79 patients included in the intention-to-treat population of the METTEN study, a phase 2 clinical trial of HER2-positive BC patients randomized to receive either metformin combined with anthracycline/taxane-based chemotherapy and trastuzumab or equivalent regimen without metformin, before surgery.

A phase 2 trial of neoadjuvant metformin in combination with trastuzumab and chemotherapy in women with early HER2-positive breast cancer: the METTEN study.

The METTEN study assessed the efficacy, tolerability, and safety of adding metformin to neoadjuvant chemotherapy plus trastuzumab in early HER2-positive breast cancer (BC). Women with primary, non-metastatic HER2-positive BC were randomized (1:1) to receive metformin (850 mg twice-daily) for 24 weeks concurrently with 12 cycles of weekly paclitaxel plus trastuzumab, followed by four cycles of 3-weekly FE75C plus trastuzumab (arm A), or equivalent regimen without metformin (arm B), followed by surgery. Primary endpoint was the rate of pathological complete response (pCR) in the per-protocol efficacy population.

A randomized adaptive phase II/III study of buparlisib, a pan-class I PI3K inhibitor, combined with paclitaxel for the treatment of HER2- advanced breast cancer (BELLE-4).

Background: Phosphatidylinositol 3-kinase (PI3K) pathway activation in preclinical models of breast cancer is associated with tumor growth and resistance to anticancer therapies, including paclitaxel. Effects of the pan-Class I PI3K inhibitor buparlisib (BKM120) appear synergistic with paclitaxel in preclinical and clinical models.

Patients And Methods: BELLE-4 was a 1:1 randomized, double-blind, placebo-controlled, adaptive phase II/III study investigating the combination of buparlisib or placebo with paclitaxel in women with human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer with no prior chemotherapy for advanced disease.

Plasma levels of trastuzumab in gastric cancer: Case report.

Introduction The use of trastuzumab with a fluoropyrimidine and platinum compound is currently the standard first-line treatment of patients with metastatic HER2-positive gastric cancer, but it appears that serum levels of trastuzumab determine the clinical effectiveness of this treatment, affecting progression-free survival and overall survival. Case report We report the case of a patient with metastatic HER2-positivegastric cancer, receiving XELOX (fluoropyrimidine and oxaliplatin) plus trastuzumab at standard doses, who presented sub-therapeutic serum levels during the first two treatment cycles and rapid disease progression (progression-free survival = 5.6 months).

Oncologists' perceptions of cancer pain management in Spain: the real and the ideal.

Aim: Studies in some countries suggest that cancer pain is often not adequately controlled, but little is known about the situation in Spain. The objective of this study was to identify medical oncologists' perceptions about pain management in their patients.

Methods: Two-round Delphi survey of 24 medical oncologists from 22 large, geographically diverse hospitals in Spain.

Zinc, copper, manganese, and iron in chronic alcoholic liver disease.

Ethanol consumption and/or liver damage may alter liver content of several trace elements, as iron, zinc, copper, and manganese. This alteration may play a role on ongoing liver fibrogenesis. Based on these facts we have determined liver, serum, and urinary Mn, Cu, Zn, and Fe levels in a group of alcoholic cirrhotics and noncirrhotics with normal renal function, comparing them with those of controls.

[Chronic liver disease exacerbated during alpha-interferon treatment].

A 27 year old male patient was referred to our clinical unit because of marked elevation of serum bilirubin (up to 15.3 mg/dl), ASAT (563 U/l) and ALAT (845 U/l) were detected after institution of therapy with alpha interferon. The patient had been previously treated because of persistent slight elevation of serum transaminases, serological markers of hepatitis B virus and hepatitis C virus being both negative.

Alcoholic withdrawal syndrome and seizures.

A study of 72 alcoholics, hospitalized for alcohol withdrawal syndrome, was undertaken to determine the incidence of seizures, their relationship with other withdrawal symptoms, the presence of brain atrophy and the relationship of this last with withdrawal intensity severity. Sixty-seven (93%) were male and the mean age was 44.9 +/- 1.

Functional decline and nutritional status in a hospitalized geriatric population: sequential study.

We analyzed the relations between nutritional status and several measures of the ability to perform the normal activities of daily living (ADL) in a long-term institutionalized geriatric population and also studied whether changes in this ability, as found ten months later, were associated with changes in the nutritional status. Nutritional status was assessed using objective anthropometric measurements (triceps skinfold, mid upper-arm circumference, midarm muscle area [AMA], midarm fat area [AFA]) and subjective clinical features (temporal muscle atrophy [TMA] and Bichat's fat atrophy [BFA]). The capacity to perform ADL was analyzed considering ability to eat and to walk, dental status, and mental performance status.

Computerized liver imaging: relationship with quantitatively estimated histological parameters in liver cirrhosis.

In liver cirrhosis, increased splenic uptake of radiocolloid, causing the liver-to-spleen (L/S) ratio to decrease, is a characteristic finding, especially during advanced illness. Histologically, advanced liver cirrhosis shows progressive replacement of hepatic parenchyma by fibrous tracts, making it possible to quantify both image and histological parameters. On this basis, the authors performed this study in 39 alcoholic cirrhotic patients in order to determine the relationship between the L/S ratio and right-to-left hepatic lobe ratio (RL/LL) and the degree of fibrosis, fat droplet area, total fat amount, and hepatocyte area.

Hepatocyte and nuclear areas and fatty infiltration of the liver in chronic alcoholic liver disease.

In 117 patients affected by chronic alcoholic liver disease, we have histomorphometrically determined hepatocyte and nuclear areas, total amount of fat and total amount of fibrosis, comparing them with the following clinical and biochemical parameters: ascites, encephalopathy, jaundice, spiders, collateral circulation, splenomegaly, prothrombin activity, serum albumin, gammaglobulin, bilirubin, ASAT, ALAT, GGT, leukocyte and platelet count, and daily consumption of ethanol. Both hepatocyte and nuclear areas closely correlated with most of the parameters indicative of hepatic function derangement, whereas fat amount correlated with them inversely, but positively with the daily consumption of ethanol. The degree of fibrosis was greater in patients with a worse hepatic function, and there was a direct relationship between the degree of fibrosis and hepatocyte and nuclear areas, and an inverse one between the degree of fibrosis and the total amount of fat.

Effect of propylthiouracil on liver cell development in the male albino mouse: protective effect against ethanol-induced alterations.

The aim of the present study is to analyze whether the addition of propylthiouracil reverts the influence of ethanol on the development of periportal and pericentral hepatocytes and their nuclei in male albino mice. Propylthiouracil-treated animals showed decreased cellular and nuclear areas when compared with the control animals, except for the 180-day-old animals, whose pericentral cells and nuclei were greater than those of the controls and exhibited fatty infiltration. Pericentral hepatocytes and nuclei of the ethanol-fed animals showed an increase of their sizes, especially in 180-day-old animals.

Alcohol-induced hypogonadism: reversal after ethanol withdrawal.

Serum testosterone, FSH, LH and prolactin levels have been determined in a group of 32 non-cirrhotic heavy drinkers at 9 and 21 h of the 1st, 3rd, 6th, 11th and 15th days after the onset of a florid ethanol withdrawal syndrome. In addition, serum steroid hormone binding globulin (SHBG) levels were determined at the 1st and 15th days. Serum levels of all these hormones were also determined in a control group of 15 healthy male volunteers.