HMGA2 is regulated by LIN28 and BRCA1 in human placental cells.

The chromatin associated transcription factor HMGA2 is a downstream target of let-7 miRNAs and binds to chromatin to regulate gene expression. Inhibition of let-7 miRNAs by RNA-binding proteins LIN28A and LIN28B is necessary during early embryogenesis to ensure stable expression of HMGA2. In addition to LIN28, HMGA2 is regulated by a BRCA1/ZNF350/CtIP repressor complex. In normal tissues, the BRCA1/ZNF350/CtIP complex binds to the HMGA2 promoter to prevent transcription. However, in many cancers the oncomiR miR-182 targets BRCA1, preventing BRCA1 translation and allowing for increased HMGA2. Little is known about the regulation of HMGA2 during early placental development; therefore, we hypothesized that both LIN28 and BRCA1 can regulate HMGA2 in placental cells. Using siRNA and CRISPR gene editing techniques, we found that knockdowns of both LIN28A and LIN28B increase HMGA2 levels in ACH-3P cells. These cells also demonstrated deficiencies in cell differentiation, seemingly differentiating solely towards the syncytiotrophoblast sublineage, secreting higher amounts of hCG, and displaying upregulated ERVW-1. Additionally, we found that a knockout of both LIN28A and LIN28B caused a significant increase of miR-182 and a decrease in BRCA1 allowing HMGA2 mRNA levels to increase and protein levels to remain the same. Using chromatin immunoprecipitation, we saw binding of the BRCA1 repressor complex to HMGA2. We also saw a decrease in binding to HMGA2's promoter in the LIN28A/B knockout cells. These findings suggest a novel role for BRCA1 during early human placental development.

Omental transposition flap in colorectal carcinoma: adjunctive use in prevention and treatment of radiation complications.

The versatility of the omentum has led to its use as a surgical adjunct in the total oncological management of primary and recurrent colorectal carcinoma. The omentum is used as a transposition pedicle flap, broadly based on the left gastroepiploic vascular supply. Following abdominoperineal resection or low anterior resection of the rectum, the small bowel is elevated out of the pelvis by the omental bulk. The pelvic defect is reperitonealized and the risk of pelvic small bowel adhesions is diminished. With the increasing use of postoperative radiation to the pelvis for rectal carcinoma, the tolerance to therapy may be improved and the incidence of radiation enteritis and enteropathy should be reduced. Surgical complications such as leakage from low anterior anastomoses and pelvic abscesses, which may delay or contraindicate necessary postoperative radiation, are dramatically decreased. Reconstruction of the perineum with omental flap provides adequate soft tissue bulk and contour when a radical resection has been performed. The omentum has the potential for neovascular proliferation and can act to prevent anastomotic dehiscence of intestinal anastomoses involving previously irradiated bowel. Furthermore, covering unresectable recurrent carcinoma in the pelvis and retroperitoneum with the omentum as a palliative measure provides a thick anatomical barrier against potential ureteral, bladder, and small bowel invasion and obstruction. The omental flap has been used in 24 patients with colorectal carcinoma; one flap was lost as a result of distal omental infarction in a patient with recurrent rectal carcinoma and radionecrosis of the perineum. The safety and ease of this procedure has allowed increased surgical innovation, especially in the prevention and treatment of radiation complications.

Management of osteosarcoma of the maxilla and mandible.

The treatment protocols of 30 patients with osteosarcoma of the maxilla and mandible presenting to M.D. Anderson Hospital and Tumor Institute over a 30 year period were reviewed. Of the patients who received definitive treatment at this institution, 50 percent of those with maxillary and 71 percent of those with mandibular osteosarcomas survived 5 years. Local recurrences were the major problems, whereas distant metastases occurred less frequently. All patients who died from the cancer did so within 3 years of initial treatment. Primary treatment should consist of aggressive surgical resection. Preoperative radiation therapy is used for mandibular tumors. Postoperative radiation is occasionally used for maxillary cancer. Recurrent disease should be treated by surgery, radiation or chemotherapy as indicated.

Identical cancers in husband and wife.

Eleven married couples having histologically identical malignant tumors have been encountered: two couples with melanoma; three with carcinoma of the breast; two with carcinoma of the kidney, and one couple each with fibrosarcoma; carcinoma of the floor of the mouth; carcinoma of the colon and rectum, and carcinoma of the nasopharynx. The interval until the spouse of the patient with cancer was diagnosed to have cancer was within five years in all but three instances. The clinical course of the disease tended to be similar in both husband and wife. Generally, the longer the couple had been married, the more successful was their treatment. Those tumors described, as well as those identical cancers of husband and wife previously reported, have been suggested either experimentally or indirectly to have viral relationships.

Parathyroid adenomas following irradiation.

Parathyroid adenomas have been demonstrated to occur following external head and neck irradiation. The median latency interval is 30 years. In a series of 74 consecutive patients with histologically diagnosed parathyroid adenomas, 25% gave a history of prior radiation exposure. When compared to a matched control incidence of 7.9%, statistical significance is reached at p less than 0.01. Thyroid abnormalities were present in 68% of the irradiated patients, and 30% of these were malignant. Tumor of skin, breast, and parotid gland also occurrred more frequently than expected. Forty-seven percent of the irradiated group had malignant neoplasms within the radiation field. The histopathology of the radiation-associated parathyroid adenomas is similar to that seen experimentally.

Aspiration cytology of head and neck masses.

Fine needle aspiration biopsy and cytologic examination of the aspirate were performed on 203 masses involving glandular and nodal structures of the head and neck: thyroid gland (85); salivary glands (31); and lymph nodes (87). Overall cytologic-histologic correlation was 91 per cent, with a 10 per cent false-negative rate. The ease of the procedure coupled with the rapidity of obtaining a pathologic diagnosis allows a more intelligent therapeutic approach.

Correction of taste abnormality of malignancy with intravenous hyperalimentation.

A complete remission of widely metastatic bladder carcinoma was obtained with chemotherapy in a 41-year-old man. Severe persistent anorexia led to a 33% weight loss. The anorexia correlated with an elevated sucrose recognition threshold. Following 16 days of intravenous hyperalimentation, taste sensation returned to normal, anorectic symptoms cleared, and weight gain and positive nitrogen balance resulted. There was no stimulation of tumor growth. Restoration of nutritional deficits with intravenous hyperalimentation can improve taste function and appetite so that adequate oral alimentation can be tolerated.

Cytologic findings of aspiration of tumors of the breast.

Fine needle aspiration biopsy for cytologic diagnosis has been shown to be an effective adjunct to the clinical evaluation of masses of the breast by physical examination and mammography. In addition to adequately decompressing cystic masses, the procedure has been beneficial in obtaining a pathologic interpretation of any mass that is to be observed. Preoperative knowledge of the malignant nature of a mass of the breast allows the physician to investigate more selectively the possibility of metastatic disease and to consider more intelligently treatment options. Furthermore, the psychologic agony of the unknown for the patient and her family is avoided. Although histologic confirmation is always recommended before proceeding with mastectomy, a positive cytologic diagnosis can suffice when clinically advanced carcinoma is present or when there are medical contraindications to surgical treatment. Because of the false-negative rate of aspiration cytologic diagnosis, all clinically malignant or suspicious masses should have a biopsy in the face of benign cytology. This point cannot be over emphasized and is particularly pertinent to those patients in whom high risk factors of carcinoma of the breast are present. Inconclusive aspirates should be repeated or a biopsy of the mass should be done.

Surgical treatment of nonocclusive mesenteric infarction.

Two cases of nonocclusive mesenteric vascular disease associated with stenosis of the superior mesenteric artery are described. In one patient with congestive heart failure and atrial fibrillation treated with digitalis, the first episode after a bout of sepsis was treated supportively, but a stricture of ileum secondary to full thickness intestinal infarction resulted. His second episode required emergency ileal resection for perforation. The superior mesenteric artery was subsequently reconstructed with an aortomesenteric bypass. The second patient had segmental intestinal necrosis occurring in association with superior mesenteric artery narrowing without total occlusion. These cases emphasize the importance of awareness of nonocclusive mesenteric vascular disease occurring in individuals with narrowing of the mesenteric arteries. A variety of modes of presentation are suggested. Arteriography is essential for diagnosis and, in selected cases, for therapy.

Squamous cell carcinoma of the soft palate.

Thirty-eight patients with squamous cell carcinoma of the soft palate treated between 1960 and 1975 were reviewed. Males in the seventh decade predominated. All symptomatic patients complained of sore throat and/or odynophagia. Seventy-eight percent were symptomatic less than three months. Approximately equal numbers of patients presented with T1, T2, and T3 tumors. Twenty-seven percent had cervical metastases when initially seen. The majority (89%) of patients were treated with radiation initially and the remainder (11%) received radiation therapy at the time of postsurgical recurrence with an absolute five year survival of 33%. Patients less than 60 years of age and those with small primary tumors and no neck metastases demonstrated better survival. Radiation therapy to the primary tumor and neck appears to be the preferred modality of initial treatment.