Venetoclax-based Rational Combinations are Effective in Models of -amplified Neuroblastoma.

Venetoclax is a small molecule inhibitor of the prosurvival protein BCL-2 that has gained market approval in BCL-2-dependent hematologic cancers including chronic lymphocytic leukemia and acute myeloid leukemia. Neuroblastoma is a heterogenous pediatric cancer with a 5-year survival rate of less than 50% for high-risk patients, which includes nearly all cases with amplified We previously demonstrated that venetoclax is active in -amplified neuroblastoma but has limited single-agent activity in most models, presumably the result of other pro-survival BCL-2 family protein expression or insufficient prodeath protein mobilization. As the relative tolerability of venetoclax makes it amenable to combining with other therapies, we evaluated the sensitivity of -amplified neuroblastoma models to rational combinations of venetoclax with agents that have both mechanistic complementarity and active clinical programs.

Diffuse large B-cell lymphoma of the colon with synchronous liver metastasis: a rare case report mimicking metastatic colorectal adenocarcinoma.

Background: Primary colorectal lymphoma represents a rare minority among the colonic neoplasms. Early diagnosis is often difficult because of unspecific symptoms, with subsequent delays in diagnosis and management. We describe a rare case of colonic lymphoma presenting with synchronous liver metastasis.

Struma ovarii with follicular thyroid-type carcinoma and neuroendocrine component: case report.

Struma ovarii (SO) is a slow-growing ovarian neoplasm with thyroid tissue as its predominant component. It is an uncommon neoplasm, usually asymptomatic with an unknown risk of malignant transformation. Due to difficulties in assessing the rare biological nature and the discrepancies in the reported cases, a consensus on the appropriate treatment has not been definitively reached.

Malignant PEComa: a case report with emphasis on clinical and morphological criteria.

Background: Malignant perivascular epitheliod cell tumor (PEComa) is a very rare entity composed of distinctive perivascular epitheliod cells with variable immunoreactivity for melanocytic and muscle markers. At present this neoplasm does not have a known normal cellular counterpart and the natural history is often unpredictable. Up to now, few cases of PEComa have been described and treatment modalities are still controversial, particularly in advanced conditions.

Laparoscopic colectomy in colon cancer. A single-center clinical experience.

Introduction: Aim of our study was to compare the results of the laparoscopic technique to those obtained by traditional open approach in patients with colon cancer. The advantages, disadvantages, and the contraindications (real and presumptive) of this mini-invasive approach are described, by comparing the data obtained from the international literature with our clinical experience.

Patients And Methods: From February 2000 to May 2006, we performed 73 laparoscopic colectomies for cancer in the Operative Unit of General and Laparoscopic Surgery, Department of Surgical Sciences of the University of Chieti, Italy.

[Pseudosarcomatous lesions: report of two cases].

Of unknown etiology, mainly located on the upper limbs, the nodular fasciitis nowadays is considered as a reactive inflammatory lesion more than a neoplastic one. With very few symptoms, it can be diagnosed through histology and the extent of the excision is related to the report of the pathological examination.

Segmental resection of the third and fourth portions of the duodenum after intestinal derotation for a GIST: a case report.

We describe a case in which segmental resection of the third and fourth portion of the duodenum was performed for a very rare duodenal gastrointestinal tumor (GIST). A 58-year old man presented with melena. Capsule endoscopy revealed a pathological bleeding of the duodenum and oral contrast-CT enema confirmed a lesion of the duodenum inferior knee, measuring 3.

[Primary lymphoma of the breast].

Primary non-Hodgkin's lymphoma of the breast accounts for fewer than 3% of extranodal lymphomas. As compared to extranodal lymphomas in other sites they are characterised by more rapid progression and a worse prognosis. The aim of the study was to investigate 5 cases of primary lymphoma of the breast and review previous studies in a search for any preoperative characteristics that could assist in the management of lymphoma of the breast.

Beyond U0126. Dianion chemistry leading to the rapid synthesis of a series of potent MEK inhibitors.

Employing phenylmalonitrile dianion chemistry, a large number of analogues of MEK inhibitor lead SH053 (IC(50)=140 nM) were rapidly synthesized leading to single digit nM inhibitors, displaying submicromolar AP-1 transcription inhibition in COS-7 cells. Compound 41, exhibiting a MEK IC(50)=12 nM showed ip activity in a TPA-induced ear edema model with an ED(50)=5 mg/kg.

[A case of colonic multiple lipoma].

The Authors, after a review of the literature, report a case of multiple lipomas of the left colon. They analyse the diagnostic, pathogenetic and therapeutic features of this rare pathology.

[Diagnosis and therapy of severe acute colitis, still an open issue. Our experience].

From a review of a series of 12 cases of whom 52 operated and of the literature, the Authors discuss about aetiology, pathogenesis and diagnosis of severe colitis. Clinical and laboratory findings, CT and plain films of the abdomen and at last colonoscopy should be evaluated very carefully for certainty diagnosis of a severe acute colitis or toxic megacolon. They suggest a multidisciplinary approach as fundamental for medical management, for indications and correct timing of surgical procedures and to decrease postoperative morbility and mortality.

[Clinical study of aortic co-involvement in lumbo-aortic lymph node metastasis of testicular carcinoma].

The Authors review the international literature about the frequency of vascular involvement (inferior vena cava and aorta) in the lymph node lumbo-aortic metastases of the testicular neoplasm. They report a case of a patient with an aortic involvement from lymph node metastases of a mixed (seminoma and germ cell) cancer of the left testis. They performed en bloc resection of the bulky metastases including the aorta involved.

[Juvenile papillomatosis of the breast].

The PJ, introduced by Rosen in the 1980, is a benign and localized mammary lesion in female under 30 years old. The most important clinical and histological features are: Diagnosis in juvenile age. A mass clinically localized.

[Our experience with duodenal tumors].

The authors report 3 cases of benign duodenal tumors and one case of duodenal cancer. In two cases the benign tumors were adenomatous polyps, in one case with signs of dysplasia. One case of benign tumor was a lipoma.

[Our experience with pheochromocytoma].

The authors report cases of pheocromocytomas operated in the period 1991-1997. 16 of these patients presented a monolateral pheocromocytoma, 1 a bilateral. A patient had a malignant evolution, one patient presented an extrasurrenal para-aortic localization.

MEK inhibitors: the chemistry and biological activity of U0126, its analogs, and cyclization products.

In search of antiinflammatory drugs with a new mechanism of action, U0126 was found to functionally antagonize AP-1 transcriptional activity via noncompetitive inhibition of the dual specificity kinase MEK with an IC50 of 0.07 microM for MEK 1 and 0.06 microM for MEK 2.

Inhibition of MAP kinase kinase prevents cytokine and prostaglandin E2 production in lipopolysaccharide-stimulated monocytes.

Activation of the extracellular signal-regulated kinase (ERK) pathway has been shown to occur in monocytes following stimulation with LPS. However, the importance of this event for monocyte function is not clear. To address this issue, we used the novel MAP/ERK kinase (MEK) inhibitor, U0126.

Identification of a novel inhibitor of mitogen-activated protein kinase kinase.

The compound U0126 (1,4-diamino-2,3-dicyano-1, 4-bis[2-aminophenylthio]butadiene) was identified as an inhibitor of AP-1 transactivation in a cell-based reporter assay. U0126 was also shown to inhibit endogenous promoters containing AP-1 response elements but did not affect genes lacking an AP-1 response element in their promoters. These effects of U0126 result from direct inhibition of the mitogen-activated protein kinase kinase family members, MEK-1 and MEK-2.

Ultrastructural Studies of the Effects of Allium sativum on Phytopathogenic Fungi in vitro.

A study was made of the effects of garlic on the development of mycelium in the following phytopathogenic fungi: Fusarium solani (Mart.) Sacc., Rhizoctonia solani Kühn, Pythium ultimum Trow var.

[Medullary carcinoma of the thyroid].

Medullary thyroid carcinoma represents 4-8% of thyroid malignancies; regional nodal involvement is commonly found, even at the time of first surgical approach. In these patients after surgical resection, other therapeutic choices are really limited. The Authors evaluated their experience in the period 1981-1994, concerning 14 patients, 9 females and 5 males, all affected with sporadic MTC.

An ELISA assay for murine interleukin-1 beta.

An ELISA assay was developed for murine IL-1 beta (mIL-1 beta) using a polyclonal antibody generated in rabbits. The antibody was purified by affinity chromatography on protein A coupled to Sepharose followed by chromatography on mIL-1 beta coupled to Sepharose. The protein A and affinity purified populations were compared using radiolabeled mIL-1 beta and the results used to develop the conditions for the ELISA.

[The prevention of venous thromboembolism in Italy].

A questionnaire concerning the prophylaxis of venous thromboembolism was filled in by 326 surgical departments in Italy. In 58% the prophylaxis was routinely used and in 29% more than one method was used. The most used method of prevention was subcutaneous heparin followed by elastic compression.

[Goiter recurrences after surgical resection].

A personal experience about 135 pz. with non-toxic goitre treated by mono o bilateral thyroidectomy and followed during 5 years (2-8) to evaluate the incidence of recurrences is reported. The recurrences were 10.