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Cervical cancer is a malignant epithelial tumor that forms in the uterine cervix. Most cases of cervical cancer are preventable through human papilloma virus (HPV) vaccination, routine screening, and treatment of precancerous lesions. However, due to inadequate screening protocols in many regions of the world, cervical cancer remains the fourth-most common cancer in women globally. The complete NCCN Guidelines for Cervical Cancer provide recommendations for the diagnosis, evaluation, and treatment of cervical cancer. This manuscript discusses guiding principles for the workup, staging, and treatment of early stage and locally advanced cervical cancer, as well as evidence for these recommendations. For recommendations regarding treatment of recurrent or metastatic disease, please see the full guidelines on NCCN.org.

Endometrial carcinoma is a malignant epithelial tumor that forms in the inner lining, or endometrium, of the uterus. Endometrial carcinoma is the most common gynecologic malignancy. Approximately two-thirds of endometrial carcinoma cases are diagnosed with disease confined to the uterus. The complete NCCN Guidelines for Uterine Neoplasms provide recommendations for the diagnosis, evaluation, and treatment of endometrial cancer and uterine sarcoma. This manuscript discusses guiding principles for the diagnosis, staging, and treatment of early-stage endometrial carcinoma as well as evidence for these recommendations.

Mucin domains are densely O-glycosylated modular protein domains that are found in a wide variety of cell surface and secreted proteins. Mucin-domain glycoproteins are known to be key players in a host of human diseases, especially cancer, wherein mucin expression and glycosylation patterns are altered. Mucin biology has been difficult to study at the molecular level, in part, because methods to manipulate and structurally characterize mucin domains are lacking. Here, we demonstrate that secreted protease of C1 esterase inhibitor (StcE), a bacterial protease from Escherichia coli, cleaves mucin domains by recognizing a discrete peptide-and glycan-based motif. We exploited StcE's unique properties to improve sequence coverage, glycosite mapping, and glycoform analysis of recombinant human mucins by mass spectrometry. We also found that StcE digests cancer-associated mucins from cultured cells and from ascites fluid derived from patients with ovarian cancer. Finally, using StcE, we discovered that sialic acid-binding Ig-type lectin-7 (Siglec-7), a glycoimmune checkpoint receptor, selectively binds sialomucins as biological ligands, whereas the related receptor Siglec-9 does not. Mucin-selective proteolysis, as exemplified by StcE, is therefore a powerful tool for the study of mucin domain structure and function.O-glycosylation | mucin | protease | glycoproteomics | Siglec

The NCCN Guidelines for Cervical Cancer provide interdisciplinary recommendations for treating cervical cancer. These NCCN Guidelines Insights summarize the NCCN Cervical Cancer Panel's discussion and major guideline updates from 2014 and 2015. The recommended systemic therapy options for recurrent and metastatic cervical cancer were amended upon panel review of new survival data and the FDA's approval of bevacizumab for treating late-stage cervical cancer. This article outlines relevant data and provides insight into panel decisions regarding various combination regimens. Additionally, a new section was added to provide additional guidance on key principles of evaluation and surgical staging in cervical cancer. This article highlights 2 areas of active investigation and debate from this new section: sentinel lymph node mapping and fertility-sparing treatment approaches.

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Vulvar cancer is a rare gynecologic malignancy. Ninety percent of vulvar cancers are predominantly squamous cell carcinomas (SCCs), which can arise through human papilloma virus (HPV)-dependent and HPV-independent pathways. The NCCN Vulvar Cancer panel is an interdisciplinary group of representatives from NCCN Member Institutions consisting of specialists in gynecological oncology, medical oncology, radiation oncology, and pathology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Vulvar Cancer provide an evidence- and consensus-based approach for the management of patients with vulvar SCC. This manuscript discusses the recommendations outlined in the NCCN Guidelines for diagnosis, staging, treatment, and follow-up.

Like human gliomas, the rat 9L gliosarcoma secretes the immunosuppressive transforming growth factor p (TGF-P3). Using the 9L model, we tested our hypothesis that genetic modification of glioma cells to block TGF-P8 expression may enhance their immunogenicity and make them more suitable for active tumor immunotherapy. Subcutaneous immunizations of tumor-bearing animals with 9L cells genetically modified to inhibit TGF-j3 expression with an antisense plasmid vector resulted in a significantly higher number of animals surviving for 12 weeks (11/11, 100%) MATERIALS AND METHODS Construction of Vectors and Genetic Modification of 9LCells. TGF-132 antisense vector. To generate the TGF-,3 antisense vector, a DNA fragment containing bases 1-870 of simian TGF-,32 cDNA (15) was ligated in reverse orientation in the HindIII-XhoI sites of the pCEP-4 vector (Invitrogen) (Fig. 1). Expression of the antisense molecule in pCEP-4 is driven by the cytomegalovirus promoter of the vector. The pCEP-4 vector also contains the hygromycin resistance gene driven by the herpes simplex virus thymidine kinase promoter, the Epstein-Barr virus origin of replication, and the gene for the Epstein-Barr virus nuclear-associated antigen protein 1. Genetic modification of 9L cells with the pCEP-4/TGF-/3 antisense vector or an empty pCEP-4 control vector was performed by electroporation using a BTX (San Diego) electroporator (16). Pools of clones were selected with hygromycin at 200 ,ug/ml (Sigma). TGF-3 secretion was measured by the previously described TF-1 cell bioassay (17). The growth of TF-1 cells (from Mire-Sluis, ref. 17) is inhibited in a dosedependent manner by . To confirm the specificity of TF-1 growth inhibition by TGF-13, the conditioned 9L supernatants were incubated with neutralizing concentrations of turkey anti-TGF-f3 antiserum. Normal (nonimmune) turkey sera was used as a negative control. Standard curves generated with known concentrations of purified TGF-13 (Sigma) served as a positive control and permitted quantification of TGF-3 levels in the test samples. Antisense inhibition of TGF-,3 has been maintained for >1 yr and has been confirmed by the TF-1 bioassay.IL-2 vector. The construction of LNCX/IL-2 retroviral has been described (18). Virus-containing supernatant from PA317/LNCX/IL-2 packaging cell line was used to transduce the 9L and TGF-/32 antisense-modified 9L cell cultures as described (18). The levels of interleukin 2 (IL-2) in tissue culture supernatants of IL-2-transduced cells were measured by previously described ELISA, and the IL-2 biological activity was confirmed as described (18