Gap junction beta-4 accelerates cell cycle progression and metastasis through MET-AKT activation in pancreatic cancer.

Despite continuing advances in the development of effective new therapies, including immunotherapies, the prognosis of pancreatic cancer remains extremely poor. Gap junction proteins have become attractive targets for potential cancer therapy. However, the role of gap junction beta-4 (GJB4) protein remains unexplored in pancreatic cancer. Through bioinformatic analyses we discovered pancreatic cancer tissues showed higher levels of GJB4 transcripts compared to normal pancreatic tissues and this had a negative effect on overall survival in patients that had pancreatic cancer. The high expression of nuclear GJB4 was identified as a negative prognostic factor in such patients. Knockdown of GJB4 in cultured pancreatic cancer cells resulted in G0/G1 arrest followed by decreased cell proliferation and suppression of metastatic potential. The overexpression of GJB4 accelerated cell proliferation, migration, and invasion in a SUIT-2 cell line, whereas MET inhibitor canceled the acceleration. GJB4 suppression with siRNA significantly inhibited tumor growth in a mouse xenograft model. Mechanistically, suppression of GJB4 inhibited MET-AKT activities. Such data suggest that targeting the GJB4-MET axis could represent a promising new therapeutic strategy for pancreatic cancer.

Successful Treatment With Venetoclax Plus Azacytidine Combined With Radiation Therapy and Donor Lymphocyte Infusion in a Patient With Extramedullary Relapse of Acute Myeloid Leukemia After Stem Cell Transplantation.

Extramedullary (EM) relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia (AML) is rare and causes systemic relapse. Consequently, the prognosis is very poor because limited treatment is feasible in post-transplant patients. The efficacy and safety of venetoclax (VEN), a newly developed oral inhibitor of B-cell leukemia/lymphoma-2, plus azacytidine (AZA) in patients newly diagnosed with AML who are ineligible for intensive chemotherapy have been reported. We report a case in which VEN + AZA salvage treatment following radiation therapy and donor lymphocyte infusion afforded promising results in a patient with AML who showed post-allo-HSCT EM relapse.

Successful Pregnancy and Fetal Outcomes Following Brentuximab Vedotin for Early Relapsed Classic Hodgkin Lymphoma After Autologous Stem Cell Transplant.

Brentuximab vedotin (BV), an anti-CD30 antibody with monomethyl auristatin E conjugate, has shown clinical effects against relapsed/refractory classic Hodgkin lymphoma (cHL) and hence is widely used in the clinical setting. We report a special clinical case of successful pregnancy and fetal outcome in a patient with cHL who achieved long-term remission with BV for early relapse after an autologous stem cell transplant (auto-SCT). A 27-year-old woman with advanced cHL achieved complete response (CR) after six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) regimen. Embryos obtained from intracytoplasmic sperm injection were cryopreserved before the initiation of induction chemotherapy. Despite achieving a second CR following intensive salvage chemotherapy, auto-SCT, and radiotherapy, she relapsed again six months after transplantation. BV monotherapy was administered as salvage therapy. She completed 16 cycles of BV and achieved CR. Six months after BV completion, she expressed her desire to bear a child. She achieved pregnancy through third in vitro fertilization and embryo transfer and delivered a healthy baby. BV may provide a potentially curative treatment for patients with cHL relapsed after auto-SCT. Pregnancy should be avoided during BV administration up to a certain period after the end of administration. Fertility preservation is important for adolescent and young adult cancer survivors, and patients should be informed of cancer-related infertility and fertility preservation options prior to the initiation of cancer treatment.

High-grade B-cell lymphoma, not otherwise specified, presenting as primary peritoneal lymphomatosis and successfully treated with dose-adjusted EPOCH-R.

Peritoneal lymphomatosis (PL) is a rare lymphoma-associated condition defined as the dissemination of lymphoma cells in the peritoneum. An 82-year-old man presented with abdominal pain, heartburn, and high fever. Radiological findings, including positron emission tomography-computed tomography (PET-CT), and gastrointestinal fiberscopy, showed diffuse thickening of the peritoneum, omentum, and mesentery; however, no lymphadenopathy, hepatosplenomegaly, or gastrointestinal lesions were observed. Under suspicion of peritonitis carcinomatosa of unknown origin, exploratory laparoscopy was performed that revealed multiple white nodules and masses on the surfaces of the peritoneum, mesentery, and intestinal serosa. The histopathological and cytogenetic findings of the peritoneum revealed high-grade B-cell lymphoma, not otherwise specified, and a gain of MYC by fluorescence in-situ hybridization. The patient was treated with two cycles of R-CHOP therapy, followed by six cycles of dose-adjusted EPOCH-R therapy, and a complete metabolic response was confirmed by PET-CT. Since there are no specific radiological findings to confirm the diagnosis of PL, a histopathological diagnosis is usually required. Most PL exhibit an aggressive lymphoma phenotype and can be cured by appropriate chemotherapy. Therefore, early diagnosis and treatment are desirable.