LyeTx I-b Peptide Attenuates Tumor Burden and Metastasis in a Mouse 4T1 Breast Cancer Model

Cationic anticancer peptides have exhibited potent anti-proliferative and anti-inflammatory effects in neoplastic illness conditions. LyeTx I-b is a synthetic peptide derived from Lycosa erythrognatha spider venom that previously showed antibiotic activity in vitro and in vivo. This study focused on the effects of LyeTxI-b on a 4T1 mouse mammary carcinoma model. Mice with a palpable tumor in the left flank were subcutaneously or intratumorally injected with LyeTx I-b (5 mg/kg), which significantly decreased the tumor volume and metastatic nodules. Histological analyses showed a large necrotic area in treated primary tumors compared to the control. LyeTxI-b reduced tumor growth and lung metastasis in the 4T1 mouse mammary carcinoma model with no signs of toxicity in healthy or cancerous mice. The mechanism of action of LyeTx I-b on the 4T1 mouse mammary carcinoma model was evaluated in vitro and is associated with induction of apoptosis and cell proliferation inhibition. Furthermore, LyeTx I-b seems to be an efficient regulator of the 4T1 tumor microenvironment by modulating several cytokines, such as TGF-β, TNF-α, IL-1β, IL-6, and IL-10, in primary tumor and lung, spleen, and brain. LyeTx I-b also plays a role in leukocytes rolling and adhesion into spinal cord microcirculation and in the number of circulating leukocytes. These data suggest a potent antineoplastic efficacy ofLyeTx I-b.

Pathogenesis, Diagnosis, and Management of Splenogonadal Fusion: A Literature Review

Introduction. Splenogonadal fusion is a rare congenital anomaly, defined by the presence of ectopic splenic tissue caused by an abnormal connection between the spleen and the gonad or mesonephrotic derivatives during the embryonic period. Materials and Methods. By reporting an observational case and performing a review of the literature according to the CARE guidelines (using the PubMed database and guidelines from urology, general surgery, and pediatric learned societies), we present the embryological genesis of the splenogonadal fusion, the associated anatomical anomalies, and the diagnostic procedure. Observation. We report the case of a patient aged 45, with no notable history, reporting left testicular pain. A small nodule on the upper pole of the left testicular was clinically palpable. Tumor markers were normal, and scrotal ultrasound depicted a hypoechoic hypervascular nodule measuring 8∗6∗8 mm. After validation in a multidisciplinary oncology consultation meeting and opinion from a uro-andrologist expert, the patient underwent an inguinal lumpectomy with an extemporaneous examination which did not objectify any signs of malignancy. Ultimately, it is a normal spleen tissue in the testicular ectopic position. Discussion. Splenogonadal fusion corresponds to a rare congenital malformation; less than 200 cases have been published in the literature, most often affecting boys, with a sex ratio of 15/1. Two types are described, depending on the continuity of the link between the orthotopic spleen and the gonad: the continuous and discontinuous forms. In a third of the cases, there are associated congenital malformations and particularly in the continuous forms (44 to 50% of the cases): anomalies of the limbs, micrognathia, microgyria, and hepatic and digestive abnormalities. Cryptorchidism is associated with the continuous form in 31% of cases. The preoperative diagnosis remains difficult because of its morphological and clinical characteristics suggesting a tumor process.

Ileocecal Intussusception in an Adult Secondary to a Colon Adenocarcinoma: A Case Report and Literature Review

Intussusception is defined as telescoping of a proximal segment of the gastrointestinal tract into a distal segment caused by an organic lesion usually on the bowel that functions as a guiding point been pulled towards a distal segment due to normal peristalsis. It is rare in adults, and it represents only 5% of all intussusceptions which for the most part has been reported in the rectosigmoid colon and mostly diagnosed during surgery. We present a patient with intermittent abdominal pain and intermittent mild symptoms of bowel obstruction who reveals in imaging studies an ileocecal intussusception and due to his age, loss of weight, and a palpable tumor, a malignancy as the cause of intussusception was suspected. The histopathological study reported a colon adenocarcinoma. Although it is possible to reduce an intussusception, this should be avoided in adults due to a high malignancy rate and a perforation risk of the piece that might cause tumor cell dissemination. Taking in consideration what has been reported in literature and the colon cancer epidemiology, we should always keep in mind the possibility of a malignant tumor in a colonic intussusception finding, regardless if it is diagnosed during preoperative by imaging studies in a scheduled patient or if it is found during an emergency laparotomy.

Primary Myeloid Sarcoma of the Ileum and Mesentery Causing Small Bowel Obstruction: Case Report and Literature Review

Myeloid sarcoma (extramedullary myeloblastoma, granulocytic sarcoma, chloroma) is an extramedullary isolated malignant tumor of myeloblasts and immature myelocytes. It can occur anywhere in the body as a solitary tumor or can be accompanied with acute myeloid leukemia. We are presenting a case of a young male patient that presented with sings of a small bowel obstruction and a palpable tumor mass in the abdomen. After uneventful postoperative period, the immunohistochemistry analysis reported an extramedullary myeloid sarcoma since a normal bone marrow biopsy was revealed.

ARRY-520 Combined With Pomalidomide Displays Enhanced Anti-Tumor Activity In Preclinical Models Of Multiple Myeloma

Inhibitors of Kinesin Spindle Protein (KSP), a mitosis-specific motor protein, represent a novel class of targeted anti-cancer therapies that have demonstrated clinical activity in hematological cancers. Inhibition of KSP results in the formation of aberrant monopolar spindles, mitotic arrest, and rapid apoptosis through degradation of the survival protein Mcl-1. The majority of KSP-inhibitor sensitive cells are proliferating hematopoietic cells which are dependent on Mcl-1 for survival. ARRY-520, a highly selective KSP inhibitor, is currently in Phase 2 clinical studies in patients with relapsed and refractory multiple myeloma. To date, ARRY-520 has demonstrated a well-tolerated safety profile and clinical activity both alone and in combination with bortezomib, dexamethasone, or carfilzomib in heavily pretreated patients. Updated clinical data will be disclosed at this meeting in separate abstracts. While prior preclinical studies have shown that ARRY-520 is additive or synergistic when combined with bortezomib in several in vivo models of multiple myeloma, the combinability of ARRY-520 with other myeloma standards of care, such as immunomodulatory drugs (IMiD), has not been thoroughly investigated. In the present studies, we have evaluated the combination utility of ARRY-520 and pomalidomide, an IMiD recently approved by the FDA, in preclinical models of multiple myeloma. Our findings show that the combination of ARRY-520 (12.5 mg/kg, IP, D1, 2) with pomalidomide (10 mg/kg, IP, QD) is significantly more active than either monotherapy alone in several in vivo models of multiple myeloma. In particular, complete responses and cures were observed in two models. In the RPMI-8226 model, a 100% cure rate was observed with the combination regimen as compared to a 0% cure rate for either monotherapy (cure is defined as no palpable tumor 100 days from study initiation). Likewise, in the JJN3 model a 100% complete response rate was observed with the combination regimen versus a 0% complete response rate for either monotherapy (complete response is defined as no palpable tumor for 2 consecutive tumor measurements). Notably, similar combination efficacy was also observed in the RPMI-8226 model at full and significantly reduced doses of both ARRY-520 and pomalidomide, supporting a synergistic interaction between these drugs. Characterization of the mechanism underlying the anti-tumor activity of this combination is currently being explored. The combination regimen was well tolerated causing no significant enhancement of body weight loss (not exceeding 10% for any group). Additionally, hematology analysis showed that the combination regimen caused no significant increase in thrombocytopenia or leukopenia. Consistent with clinical findings, both single agent ARRY-520 and pomalidomide caused neutropenia while the combination of these drugs moderately enhanced these effects. Pharmacokinetic studies confirmed that administration of pomalidomide with ARRY-520 does not alter the exposure of either compound, suggesting that the mechanism of enhanced anti-tumor activity is dependent upon pharmacodynamic rather than pharmacokinetic effects. Taken together, these findings show that the novel combination of ARRY-520 and pomalidomide is a well-tolerated and synergistic preclinical regimen that warrants investigation in future clinical trials in patients with multiple myeloma. Disclosures: Humphries: Array BioPharma: Employment. Anderson:Array BioPharma: Employment. Williams:Array BioPharma: Employment. Rieger:Array BioPharma: Employment. Tunquist:Array BioPharma: Employment. Walker:Array BioPharma: Employment.

Primary Malignant Melanoma of the Stomach

We report a 54-year-old patient with a complaint of weakness, abdominal pain and weight loss. During the clinical examination a palpable tumor resistance in the abdomen was found as well as iron deficiency anemia. Gastroscopy showed an exulcerated, dark brown, fungiform tumor about 4 cm in diameter at the great curve of stomach. Endoscopic biopsy revealed the diagnosis of malignant melanoma by demonstrating the presence of melanin containing tumor cells in gastric mucosa. The patient underwent subtotal gastrectomy, appendectomy and splenectomy. The diagnosis of gastric melanoma with regional lymph node metastases, as well as metastases in appendix adjacent tissue was confirmed by histology and immunohistochemistry. In three years follow up period patient developed cerebral and retroauricular subcutaneous metastases that were treated by surgery, adjuvant chemotherapy and radiotherapy. Finally, an explorative laparotomy was revealed advanced intraabdominal tumor dissemination with dark pigmented ascites. Concerning that all available diagnostic procedures failed to prove other site of melanoma, presented case was considered as primary gastric melanoma as a possible rare site of tumor.